Serum Sirtuin1 Research Articles

Evaluation of sirtuin 1 as a predictor of cardiovascular outcomes in diabetic patients with limb-threatening ischemia.

Chronic limb-threatening ischemia (CLTI) significantly increases the risk of major adverse limb events (MALE) and major adverse cardiac events (MACE) after lower extremity revascularization (LER). This study aims to identify novel biomarkers that help to further reduce the risk of postoperative cardiovascular complications. In this prospective, nonrandomized, observational study, baseline serum levels of sirtuin 1 (SIRT1) were assessed in 147 diabetic patients scheduled for LER due to CLTI, and participants were followed for the occurrence of MALE and MACE over 12 months. Fifty-three patients experienced MALE, and 33 experienced MACE within the follow-up period. Lower baseline SIRT1 levels were significantly associated with an increased risk of MALE and MACE, independent of other risk factors. The ROC curve analysis identified a SIRT1 cutoff of 3.79 ng/mL for predicting the risk of MALE. Moreover, incorporating SIRT1 into predictive models significantly enhanced the accuracy of predicting adverse outcomes. Results suggest serum SIRT1 is a potential independent marker for predicting MALE and MACE in diabetic patients with CLTI undergoing LER. Further research is needed to clarify the mechanistic pathways in which SIRT1 may influence cardiovascular outcomes, and the role of this novel biomarker in the management of PAD and CLTI among patients with diabetes.

Correlation Between Serum and Tissue SIRT1 Levels in Patients With Esophageal Squamous Cell Carcinoma.

Identifying prognostic and molecular markers as therapeutic targets for esophageal squamous cell carcinoma (ESCC) could enhance the efficacy of multidisciplinary treatments. While tissue expression of sirtuin 1 (SIRT1) has been linked to tumor progression in ESCC, prognostic significance of serum SIRT1 levels and their correlation with tissue SIRT1 remains unexplored. This study aimed to investigate the correlation between serum and tissue SIRT1 levels in patients with ESCC. A total of 38 patients diagnosed with ESCC who were untreated preoperatively were recruited for this study. SIRT1 expression in the surgical specimens was assessed through immunostaining, while serum SIRT1 levels were measured using an enzyme-linked immunosorbent assay. We analyzed the association between tissue and serum SIRT1 levels, clinicopathological features, and patient prognosis. Positive SIRT1 expression in tissue was significantly associated with deeper tumor depth (p=0.020). It was also significantly associated with poorer overall survival (OS) and relapse-free survival (RFS) (p=0.041 and p=0.012, respectively). Elevated serum SIRT1 levels were significantly correlated with increased tumor depth and weight loss (p=0.012 and p=0.030). While higher serum SIRT1 levels tended to be associated with poorer OS (p=0.069), no significant correlation was found between SIRT1 expression in tissue and its concentration in serum. SIRT1 tissue expression may be a valuable prognostic marker in ESCC. However, the clinical significance of serum SIRT1 levels appears to differ from that of its tissue expression. Future research is required to clarify the role of serum SIRT1 in ESCC.

The gut microbiota metabolite trimethylamine-N-oxide in children with β-thalassemia: potential implication for iron-induced renal tubular dysfunction.

Renal tubular dysfunction is common in transfusion-dependent β thalassemia (β-TM). Iron overload, chronic anemia, and hypoxia are precipitating factors for renal insult. However, gut microbiota engagement in the renal insult has not been explored. Our work aimed to assess the potential link between iron overload, gut leakage/dysbiosis, and kidney dysfunction in these children. We enrolled 40 children with β-TM and 40 healthy controls. Gut leakage/dysbiosis biomarkers (trimethylamine-N-oxide [TMAO] and fecal short-chain fatty acids [SCFAs]), oxidative stress and inflammatory biomarkers, TMAO-regulated proteins such as serum sirtuin 1 (S.SIRT1) and serum high mobility box group-1 (S.HMGB1), and tubular dysfunction biomarkers were assessed. Correlations and regression analysis were performed to assess the relation between different parameters. Iron overload, redox imbalance, and generalized inflammation were evident in children with β-TM. Renal tubular dysfunction biomarkers and S.TMAO were significantly elevated in the patient group. Furthermore, fecal SCFAs were significantly lower with upregulation of the investigated genes in the patient group. The correlation studies affirmed the close relationship between circulating ferritin, TMAO, and renal dysfunction and strongly implicated SIRT1/HMGB1 axis in TMAO action. Gut dysbiosis may have a role in the pathogenesis of renal injury in children with β-TM. Renal tubular dysfunction is a prominent health issue in β thalassemia major (β-TM). Iron overload, chronic anemia, and hypoxia are known precipitating factors. However, gut microbiota engagement in renal insult in these patients has not yet been explored. We aimed to assess potential link between iron overload, gut leakage/dysbiosis, and kidney dysfunction in β-TM children and to highlight the SIRT1/HMGB1 axis, a signal motivated by the gut microbiota-dependent metabolite trimethylamine-N-oxide (TMAO), involvement in such insults. We found that gut leakage/dysbiosis may have a role in kidney dysfunction in β-TM children by exacerbating the iron-motivated oxidative stress, inflammation, ferroptosis, and modulating SIRT1/HMGB1 axis.

Relationship between Serum Sirtuin 1 and Growth Hormone/Insulin-like Growth Factor 1 Concentrations in Children with Growth Hormone Deficiency and Idiopathic Short Stature.

Sirtuin 1 (SIRT1) inhibits growth hormone (GH) intracellular signaling for the insulin-like growth factor 1 (IGF-1) synthesis via the janus kinase (JAK)/signal transducer and activator of transcription proteins (STATs) pathway. The aim of this study was to compare SIRT1 concentrations in children with GH deficiency (GHD) and so-called idiopathic short stature (ISS, non-GH deficient), in order to determine the possible impact of changes in serum SIRT1 concentrations on the GH-IGF-1 axis. The study group included 100 short-stature children: 38 with GHD and 62 with ISS (maxGH in two stimulation tests <10 and ≥10 ng/mL, respectively). The control group consisted of 47 healthy, normal-height children. For each child, the concentrations of SIRT1, IGF-1 and insulin-like growth factor-binding protein 3 (IGFBP-3) were determined and the IGF-1/IGFBP-3 molar ratio was calculated. The level of SIRT1 was significantly higher in both groups of short children than in the controls (p < 0.0001), but there were no differences between GHD and ISS (mean ± SD: 0.89 ± 0.45 for ISS; 1.24 ± 0, 86 for GHD; and 0.29 ± 0.21 for controls). A significant negative correlation was found between SIRT1 and height standard deviation score (SDS), IGF-1 and IGF-1/IGFBP-3, but not between SIRT1 and maxGH. Elevated SIRT1 levels may serve as one of the mechanisms through which the secretion of IGF-1 is reduced in children with short stature; however, further research is required to confirm this issue.

Comprehensive assessment of cardiovascular-kidney-metabolic (CKM) syndrome: Novel tools for assessment of cardiovascular risk and kidney outcomes in long-term kidney transplant patients.

Cardiovascular (CV)-kidney-metabolic (CKM) syndrome, a newly defined entity, offers a framework for assessing CV risk. Emerging evidence suggests that histone deacetylase sirtuin-1 (SIRT1) and adipokine chemerin hold promise as CKM markers. This study aimed to explore the relationship between CKM stage, clinical parameters, and both novel and established markers of CV and renal risk. A cohort of 102 patients with long-term, stable kidney transplant (KTx) (>24 months) and median (interquartile range) follow-up of 83 (42-85) months was recruited alongside 32 healthy controls. Patients were classified into modified CKM stages following the American Heart Association guidance. Serum high-sensitivity interleukin-6 (hsIL-6), chemerin, and SIRT1 were measured using commercial immunoassay kits. The incidence of CV events (CVE), CV mortality, and permanent transfer to dialysis therapy were primary endpoints. CKM stage was associated with higher risk of CVE/CV death (HR 95% CI, 3.79 [1.16-12.42]; P = 0.03) and allograft loss (HR 95% CI, 2.05 [1.17-3.57]; P = 0.01). Elevated sirtuin-1 was associated with significantly lower risk of CV event/death (HR 95% CI, 0.11 [0.11-0.89]; P = 0.04), whereas high chemerin status was tied to dialysis risk (HR 95% CI, 5.77 [1.96-17.00]; P = 0.001) alone. In contrast to sirtuin-1, hsIL-6 and chemerin showed incremental changes across more advanced CKM stages, though statistically significant for hsIL-6 alone. In age-adjusted models for CV disease, independent associations with diabetes and total cholesterol were noted. Classifying patients based on modified CKM stages offers valuable prognostic insights for stable KTx recipients, particularly when assessing reno-cardiovascular risk. The investigated serum markers may serve as supplemental tools for refining risk stratification.

Association of lncRNA MEG3 rs941576 polymorphism, expression profile, and its related targets with the risk of obesity-related colorectal cancer: potential clinical insights

The identification of novel screening tools is imperative to empower the early detection of colorectal cancer (CRC). The influence of the long non-coding RNA maternally expressed gene 3 (MEG3) rs941576 single nucleotide polymorphism on CRC susceptibility remains uninvestigated. This research appraised MEG3 rs941576 association with the risk and clinical features of CRC and obesity-related CRC and its impact on serum MEG3 expression and its targets miR-27a/insulin-like growth factor 1 (IGF1)/IGF binding protein 3 (IGFBP3) and miR-181a/sirtuin 1 (SIRT1), along with the potential of these markers in obesity-related CRC diagnosis. 130 CRC patients (60 non-obese and 70 obese) and 120 cancer-free controls (64 non-obese and 56 obese) were enrolled. MEG3 targets were selected using bioinformatics analysis. MEG3 rs941576 was associated with magnified CRC risk in overall (OR (95% CI) 4.69(1.51–14.57), P = 0.0018) and stratified age and gender groups, but not with obesity-related CRC risk or MEG3/downstream targets’ expression. Escalated miR-27a and IGFBP3 and reduced IGF1 serum levels were concomitant with MEG3 downregulation in overall CRC patients versus controls and obese versus non-obese CRC patients. Serum miR-181a and SIRT1 were upregulated in CRC patients versus controls but weren’t altered in the obese versus non-obese comparison. Serum miR-181a and miR-27a were superior in overall and obesity-related CRC diagnosis, respectively; meanwhile, IGF1 was superior in distinguishing obese from non-obese CRC patients. Only serum miR-27a was associated with obesity-related CRC risk in multivariate logistic analysis. Among overall CRC patients, MEG3 rs941576 was associated with lymph node (LN) metastasis and tumor stage, serum MEG3 was negatively correlated with tumor stage, while SIRT1 was correlated with the anatomical site. Significant correlations were recorded between MEG3 and anatomical site, SIRT1 and tumor stage, and miR-27a/IGFBP3 and LN metastasis among obese CRC patients, while IGF1 was correlated with tumor stage and LN metastasis among non-obese CRC patients. Conclusively, this study advocates MEG3 rs941576 as a novel genetic marker of CRC susceptibility and prognosis. Our findings accentuate circulating MEG3/miR-27a/IGF1/IGFBP3, especially miR-27a as valuable markers for the early detection of obesity-related CRC. This axis along with SIRT1 could benefit obesity-related CRC prognosis.

Sirtuin-1 level and gene polymorphisms in multiple sclerosis

BackgroundSirtuin-1 (SIRT1) may affect multiple sclerosis (MS) disease. This study aimed to investigate the level of serum SIRT1, mRNA expression and genetic polymorphisms in Egyptian MS sufferers. Also, to assess its role as a possible biomarker in predicting the risk of MS and to evaluate the association between its levels and disability of MS. Measurement of SIRT1, serum level, mRNA expression level and genotyping for sirtuin-1 gene polymorphisms in 240 Egyptian subjects; 120 MS sufferers and 120 healthy control subjects.ResultsThere was a significant diminishment of level of serum sirtuin-1, and sirtuin-1 mRNA expression in MS sufferers compared to control subjects. Different sirtuin-1 single nucleotide polymorphism frequencies were statistically significant in MS sufferers compared to the control subjects. Moreover, a negative correlation of serum level of sirtuin-1 in MS sufferers with MS disease duration, disability according to Expanded Disability Status Scale (EDSS) score, cholesterol, and triglyceride serum levels. Regarding the sirtuin-1 gene polymorphisms in MS sufferers, the rs7895833 GG genotype had significant higher cholesterol, and low-density lipoprotein (LDL) levels than the GA and AA genotypes and that the rs7069102 GG genotype had a higher LDL level than the CG and CC genotypes while the rs2273773 TT genotype was significantly associated with cholesterol, and LDL levels than the TC and CC genotypes. No significant difference was detected in EDSS score comparing different sirtuin-1 genotypes among MS sufferers. In MS sufferers, rs7895833 G allele can be independently associated with cholesterol, triglycerides, and LDL levels. rs7069102 C allele can be independently associated with LDL level. With regard to rs2273773, T allele, it can be independently associated with cholesterol and LDL levels.ConclusionThere was a significant association between different sirtuin-1 gene polymorphisms and dyslipidemia which may modulate the course of MS disease. Furthermore, serum sirtuin-1 level can be considered as a possible predictor of disability in multiple sclerosis sufferers.

Sirtuin 1 serum concentration in healthy children - dependence on sex, age, stage of puberty, body weight and diet.

Sirtuin 1 (SIRT1) is known to be involved in sensing cellular energy levels and regulating energy metabolism. This study aimed to evaluate fasting serum SIRT1 levels in healthy children, and to analyse the influence of age, sex, puberty, body weight, height, and diet on its concentration. 47 healthy children aged 4-14 with weight and height within normal range and no chronic disease were included into the study. Fasting serum SIRT1 concentrations were estimated by Enzyme Linked Immunosorbent Assay (ELISA). Results showed that serum SIRT1 concentrations in healthy children did not differ with respect to sex, age, height, weight and puberty. Whereas, it appeared that a higher frequency of fruits, vegetables and dairy products consumption was associated with an increase in serum SIRT1 levels. Studying SIRT1 in the context of children's health may have implications for a broader understanding of growth processes, pubertal development, metabolic disorders and nutrition.

Effects of sirtuin 1 deficiency on trophoblasts and its implications in the pathogenesis of pre-eclampsia

Background Sirtuin 1 (SIRT1) is mainly localised in syncytiotrophoblasts and cytotrophoblasts, and is involved in pregnancy regulation. However, data on the association between SIRT1 and pre-eclampsia (PE) remains limited. This study aimed to investigate the role of SIRT1 in PE pathophysiology. Methods Placental SIRT1 expression, as well as serum SIRT1, placental growth factor (PlGF), and soluble FMS-like tyrosine kinase 1 (sFlt-1) levels, were measured using quantitative real-time polymerase chain reaction (qRT-PCR), western blotting, and enzyme-linked immunosorbent assays in 40 healthy pregnant women (NP group) and 40 women with severe PE (PE group). Additionally, the effects of SIRT1 on the migration, invasion, PlGF, and sFlt-1 secretion of HTR-8/SVneo cells were analysed. Results SIRT1 expression was significantly reduced in the placenta of patients with severe PE compared with that in healthy pregnant women. Compared with the NP group, serum SIRT1 and PlGF expression was significantly lower in the PE group; however, the expression of serum sFlt-1 was significantly higher in the PE group. Correlation analysis showed that in the PE group, placental SIRT1 protein levels positively correlated with serum PlGF levels (r = 0.468, P = .002) and negatively correlated with serum sFlt-1 levels (r = −0.542, P < .001). Cells with downregulated SIRT1 had a significantly shorter migration distance and a prominently reduced number of invasive cells compared with the corresponding negative control group, suggesting that SIRT1 deficiency may inhibit the migration and invasive ability of HTR-8/SVneo cells. The opposite results were observed after transfection with lentivirus overexpressing SIRT1. Compared with the corresponding controls, cells with downregulated SIRT1 had significantly reduced PlGF levels and significantly increased sFlt-1 levels in the cell culture supernatants, whereas SIRT1 overexpression produced the opposite results. Conclusions SIRT1 deficiency may contribute to the pathogenesis of pre-eclampsia by reducing trophoblastic migration, invasion, and PlGF secretion and increasing sFlt-1 secretion.

Ameliorating Effect of Aqueous Ginger Extract And Exercise On Insulin Resistance in Fructose Induced Type 2 Diabetic Rats Through Upregulation of Serum Sirtuin-1

Introduction:The mounting prevalence of type 2 diabetes mellitus (T2DM) in developing countries calls for an immediate need to find novel treatment strategies that not only target its underlying pathological process but are also safe and cost effective. Aims &amp;Objectives:To determine the effect of ginger supplementation, exercise and their combination on insulin resistance (IR) and levels of serum sirtuin 1 (SIRT1) in fructose induced type 2 diabetic rat model. Material &amp;Methods:This randomized controlled trial was conducted at animal laboratory of Postgraduate Medical Institute Lahore, Pakistan, from January 2021 to June 2021, in which thirty rats were randomly allocated to five groups with six rats in each.Rats belonging to group1 (Normal Control) were given normal rat chow diet. Diabetes was induced in groups 2, 3 and 4 by administering 25% fructose diet, following which, group 2 was reserved as diabetic/positive control (PC) and continued to receive 25 %fructose diet only. Animals of group 3 received aqueous ginger extract (GE), group 4 underwent swimming exercise (EX) and group 5 received their combination (GE+EX) for 8 weeks. Aqueous ginger extract was prepared in the Pharmacology lab at PGMI where 50 gm of fresh ginger was blended with 75ml of 0.9% NaCl and filtered thrice. The obtained filtrate was centrifuged at a speed of 2000 rpm for ten minutes. The clear supernatant fraction was made to reach 100 ml mark using NaCl resulting in a concentration of 500 mg/ml which was used for oral administration. Data was entered and analyzed using SPSS version 26, a p-value of ?0.05 was considered significant. Results:The results of the current study showed development of T2DM with 25% fructose supplementation in PC group, resulting in significantly high level of IR along with a significant reduction in levels of serum SIRT1. Aqueousginger extract group as well as the exercise group, both individually showed a significant reduction in IR as compared to the diabetic group and this was associated with significantly increased level of serum SIRT1 (p&lt;0.05). However, most pronounced effect was seen in the combination group having lowest level of IR associated with a statistically significant increase in SIRT1 levels (p&lt;0.05). Conclusion: Aqueousginger extract supplementation and exercise training, alone and in combination have the potential to significantly ameliorate IR in T2DM through its positive influence on serum SIRT1.However, the combination group has the most pronounced effect reflecting a potential synergistic effect of both interventions. Ginger supplementation and exercise may be introduced as safer, cost effective and natural adjunct to anti diabetic drugs hence lowering their potentially harmful side effects.

PROGNOSTIC VALUE OF SIRTUIN-1 LEVEL IN BLOOD SERUM OF PATIENTS WITH CHRONIC CORONARY SYNDROME, CHRONIC OBSTRUCTIVE PULMONARY DISEASE AND THEIR COMBINATION

The aim of the work – to compare the levels of serum sirtuin-1 SIRT1 in patients withCOPD and CCS in their isolated and combined course.Materials and methods. 60 patients diagnosed with COPD, CCS and combined courseof COPD with CCS, as well as 10 practically healthy individuals as a control group,participated in the study. The degree of severity of COPD was assessed by the frequencyof exacerbations and indicators of external respiratory function (ERF): the ratio ofFEV1 (forced expiratory volume in the first second) to FVLC (forced vital capacity of thelungs), as well as the values of FEV1 and VLC. A questionnaire was used to assess theseverity of symptoms, which included the mMRC (modified Medical Research Council),dyspnea severity scale and the COPD Assessment Test. The serum level of SIRT1 wasinvestigated by enzyme-linked immunosorbent assay using Human SIRT1 ELISAKitreagents. Statistical processing of the results was carried out using Microsoft Excel andStatistica 10.0 software.The results. A study that included measuring the level of SIRT1 in blood serum showedthe following results: in patients with COPD, the average level of SIRT1 was 5.21±1.16ng/ml, in patients with C it was 6.58±1.40 ng/ml, in patients with a combined course ofCOPD and CCS – 2.32±0.73 ng/ml. The level of SIRT1 in these groups was significantlylower compared to the control group, in which it was 12.23±1.59 ng/ml (p=0.01).&#x0D; Conclusions. In patients with COPD, CCS, or a combination of these diseases, thelevel of SIRT1 in the blood is lower compared to the control group. Close correlationsbetween the level of SIRT1 in the blood and impaired external respiration, age, symptoms(measured by the mMRC scale and the CAT assessment test), and the severity of thecourse of the disease in patients with COPD and CCS, were revealed.

Serum sirtuin1: a potential blood biomarker for early diagnosis of Alzheimer's disease.

Sirtuin 1, a nicotinamide adenine dinucleotide-dependent deacetylase that is highly expressed in the hippocampus and anterior cortex tissues related to Alzheimer's Disease pathology, can cross the blood-brain barrier and is a promising biomarker. A 1:1:1 case-control study was conducted and serum fasting blood glucose, triglyceride, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, SIRT1, IL-6, Aβ1-42, T-tau and P-tau-181 levels were evaluated in blood samples of 26 patients form the Alzheimer's Disease group, 26 patients form the mild cognitive impairment group, and 26 individuals form the normal control group. Receiver operator characteristic curves were used to evaluate the diagnostic significance. Serum SIRT1 level was significantly down-regulated in the mild cognitive impairment patients and Alzheimer's Disease patients compared with that in the normal control group (P<0.05). ROC curve analysis demonstrated that SIRT1 was a promising biomarker to distinguish Alzheimer's Disease patients from the mild cognitive impairment patients and the normal control group. In addition, SIRT1 was estimated to perform well in the diagnosis of Alzheimer's Disease ([AUC] = 0.742). In summary, the present study suggested that serum SIRT1 might be an early promising diagnostic biomarker for Alzheimer's Disease.

Correlation Between Oxidative Stress, SIRT1 Serum Level, and eGFR on Elderly

The aging network kidney causes Oxidative Stress (OS) and damages the kidney. Studies of aging kidneys keep going growing by developing sirtuin as an antiaging. Sirtuin 1 (SIRT1) is a protein implicated in several disorders including diabetes functions as an anti-aging protein. Decreased eGFR in the elderly caused by his height prevalence factor risk disease kidney at an older age. The study aims to study the correlation between oxidative stress, SIRT1 serum levels, and eGFR in the elderly. The method used in this research is observational with the cross-sectional method. The sample in this study was the whole elderly who met the inclusion and exclusion criteria, totaling 30 people. Exclusion criteria are patients with glomerulonephritis, nephropathy obstruction, nephropathy sour veins, and obesity. All patients complied requirements asked to fill informed consent form. The inspection was carried out by urinalysis ultrasound kidney and assessing serum MDA levels which were found to be higher in this study. This study showed SIRT1 and eGFR levels decreased in the elderly. There was a negative correlation with moderate correlation strength between serum MDA levels and serum SIRT1 levels and a strong correlation between serum MDA levels and eGFR in the elderly. There was a positive correlation with a moderate correlation between serum SIRT1 levels and eGFR in the elderly. SIRT1 is suggested to be examined in elderly patients with decreased eGFR, even without comorbidity.

The Association between Blood SIRT1 and Ghrelin, Leptin, and Antibody Anti-Hypothalamus: A Comparison in Normal Weight and Anorexia Nervosa.

Sirtuin 1 (SIRT1) is a sensor of cell energy availability, regulating metabolic homeostasis as well as leptin and ghrelin, and it could be considered as a potential plasmatic marker. The aim of this study was to assess whether circulating SIRT1 varies consistently with leptin, ghrelin, body mass index (BMI), and IgG reactive to hypothalamic antigens in anorexia nervosa (AN). Fifty-four subjects were evaluated: 32 with AN and 22 normal-weight control subjects. Serum levels of SIRT1, leptin, ghrelin, and IgG reactive to hypothalamic antigens were evaluated by ELISA. Results showed that serum SIRT1 is increased in patients with AN, and the amount is decreased in relation to the duration of the illness. SIRT1 concentration approaches the values obtained for the control group, although the difference is still statistically significant. A negative correlation between serum SIRT1 values and leptin or BMI values has been found. On the contrary, a positive correlation between SIRT1 and ghrelin or IgG specific for hypothalamic antigens is reported. These findings suggest that a peripheral evaluation of SIRT1 could be a possible clinical/biochemical parameter related to AN. In addition, we can assume that SIRT1 is related to autoantibody production and may correlate with the intensity/severity of AN. Thus, reducing the production of autoantibodies specific for hypothalamic cells could be a sign of improvement of the clinical condition.

The Relationship between Oxidative Status and Radioiodine Treatment Qualification among Papillary Thyroid Cancer Patients.

Total oxidative status (TOS), total antioxidant capacity (TAC), tumor protein 53 (p53), nuclear factor kappa B (NF-κB), forkhead box protein O1 (FOXO), and sirtuin 1 (SIRT1) play crucial roles in oxidative homeostasis and the progression of papillary thyroid cancer (PTC), as previously demonstrated in the literature. Therefore, profiling these markers among PTC patients may be useful in determining their eligibility for radioiodine (RAI) treatment. Since treatment indications are based on multiple and dynamic recommendations, additional criteria for adjuvant RAI therapy are still needed. In our study, we evaluated the TOS, TAC, and serum concentrations of p53, NF-κB, FOXO, and SIRT1 to analyze the relationship between oxidative status and qualification for RAI treatment. For the purpose of this study, we enrolled 60 patients with PTC allocated for RAI treatment as the study group and 25 very low-risk PTC patients not allocated for RAI treatment as a reference group. The serum TOS and SIRT1 concentrations were significantly higher in the study group compared to the reference group (both p < 0.001), whereas the TAC and p53, NK-κB, and FOXO concentrations were significantly lower (all p < 0.05). We also demonstrated the diagnostic utility of TAC (AUC = 0.987), FOXO (AUC = 0.648), TOS (AUC = 0.664), SIRT1 (AUC = 0.709), p53 (AUC = 0.664), and NF-κB (AUC = 0.651) measurements as indications for RAI treatment based on American Thyroid Association recommendations. Our study revealed that oxidative status-related markers may become additional criteria for RAI treatment in PTC patients.

Serum Versus Tissue SIRT1 as Potentially Valuable Biomarkers in Gastric Cancer.

We lack reports on the clinicopathological characteristics and prognostic value of serum sirtuin 1 (SIRT1) levels and their association with SIRT1 expression in tissues of patients with gastric cancer (GC). Thus, we investigated the pathological characteristics and prognostic values of SIRT1 tissue expression and its serum concentration in GC. Moreover, we investigated the correlation between these two factors. A total of 78 patients with GC who underwent curative gastrectomy were evaluated in this study. The expression of SIRT1 in the surgical specimens was assessed using immunohistochemistry. Serum levels of SIRT1 were measured using an enzyme-linked immunosorbent assay. The association of tissue and serum SIRT1 with the clinicopathological features and prognosis were evaluated. Positive SIRT1 tissue expression was significantly related to an advanced cancer stage (p=0.017). Furthermore, a significant relationship existed between a positive SIRT1 tissue expression and poorer overall survival (OS) and relapse-free survival (RFS) (p=0.033 and p=0.033, respectively). In contrast, serum SIRT1 levels showed no significant association with clinicopathological characteristics besides age. In addition, no significant correlation was observed between tissue SIRT1 expression and serum SIRT1 concentration. Tissue SIRT1 expression may be a valuable novel prognostic biomarker; nonetheless, further studies are required to clarify the relationship between tissue SIRT1 expression and serum SIRT1 levels in GC.

INFLAMMATORY AND ANTI-INFLAMMATORY MECHANISMS IN CHRONIC OBSTRUCTIVE PULMONARY DISEASE, CHRONIC CORONARY SYNDROME AND THEIR COMBINATION

Objective – to compare the levels of serum Sirtuin-1(SIRT1) and high-sensitivityC-reactive protein in patients with сhronic obstructive pulmonary disease (COPD) andсhronic coronary syndrome (CCS) during their isolated and combined course.Materials and methods. Sixty patients with diagnoses of сhronic obstructive pulmonarydisease (COPD), сhronic coronary syndrome (CCS), COPD in combination with CCS,and 10 practically healthy people (control group), were involved into the study.The comparison of data between samples was carried out according to the Student’st-test, the relationship between indicators was investigated using the Fisher correlationcoefficient. The calculations were carried out using Microsoft Excel software.Results. In the group of patients with COPD the level of high-sensitivity C-reactiveprotein constituted 1.47±0.31 mg/dl (p=0.02), in patients with CCS – 1.06±0.23 mg/dl(p=0.02), in patients with COPD, combined with CCS, – 2.13±0.30 mg/dL (p=0.01) thatwas significantly higher than in the control group –0.11±0.02 mg/dL (p=0.03).The results of the study of the SIRT1 level in the blood serum revealed that in the groupof patients with COPD, the level of SIRT1 constituted 5.21±1.16 ng/ml, in patients withCCS – 6.58±1.40 ng/ml, in patients with COPD combined with CCS –2,32±0.73ng/ml,that in all cases it was significantly lower than in the control group – 12.23±1.59ng/ml(р=0.01).Conclusions. Serum levels of SIRT1 were lower and high-sensitivity CRP were higher inpatients with COPD, CCS and in patients with COPD, combined with CCS, in comparisonwith the control group. There is a negative correlative relation in patients with COPD andCCS between the levels of high-sensitivity CRP and SIRT1.

Serum sirtuin-1 a potential marker in the diagnosis of rheumatoid arthritis

Introduction: To explore the value of serum sirtuin-1 (SIRT1) in the diagnosis and evaluation of joint mobility of rheumatoid arthritis (RA). Materials and Methods: Serum was randomly obtained from 212 RA patients,210 non-RA patients and 58 healthy controls in a large tertiary first-class hospital in Jiangxi province from November 2021 to June 2022. The level of serum Sirt1,anti-cyclic citrulline polypeptide antibody (anti-CCP), anti-mutant citrulline vimentin antibody (anti-MCV), rheumatoid factor (RF),high-mobility group box 1 (HMGB1), collagen triple helix repeat containing 1 (CTHRC1), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were detected by ELISA, to explore the correlation between them and their value in the diagnosis and evaluation of joint range of motion of RA and statistically analyse their diagnostic efficiency. Results: ① The level of all markers was higher in the RA group than in the non-RA group and the healthy controls (p < 0.05). ② The AUC of the SIRT1 was 0.882, second only to the anti-MCV and anti-CCP. ③ The anti-CCP showed the highest sensitivity to RA diagnosis of 0.948. The specificity and positive predictive value of SIRT1 for the diagnosis of RA were the highest, which are 0.959 and 0.934 respectively. ④ In serial combination, SIRT1/anti-CCP、SIRT1/anti-MCV showed the highest specificity.SIRT1/anti-CCP in parallel combination had the highest sensitivity. ⑤ SIRT1 showed a significant correlation with other markers and DAS28 scores (p < 0.01). Conclusion: SIRT1 can be used as a new serological marker for RA diagnosis, which has a significant correlation with RA joint mobility and has a certain reference value in RA differential diagnosis, providing a new detection basis for RA differential diagnosis.

Ketogenic Diet Increases Serum and White Adipose Tissue SIRT1 Expression in Mice.

Overnutrition and its sequelae have become a global concern due to the increasing incidence of obesity and insulin resistance. A ketogenic diet (KD) is widely used as a dietary treatment for metabolic disorders. Sirtuin1 (SIRT1), a metabolic sensor which regulates fat homeostasis, is modulated by dietary interventions. However, the influence of nutritional ketosis on SIRT1 is still debated. We examined the effect of KD on adipose tissue, liver, and serum levels of SIRT1 in mice. Adult C57BL/6J male mice were randomly assigned to two isocaloric dietary groups and fed with either high-fat KD or normal chow (NC) for 4 weeks. Serum SIRT1, beta-hydroxybutyrate (βHB), glucose, and triglyceride levels, as well as SIRT1 expression in visceral (VAT), subcutaneous (SAT), and brown (BAT) adipose tissues, and in the liver, were measured. KD-fed mice showed an increase in serum βHB in parallel with serum SIRT1 (r = 0.732, p = 0.0156), and increased SIRT1 protein expression in SAT and VAT. SIRT1 levels remained unchanged in BAT and in the liver, which developed steatosis. Normal glycemia and triglycerides were observed. Under a KD, serum and white fat phenotypes show higher SIRT1, suggesting that one of the molecular mechanisms underlying a KD's potential benefits on metabolic health involves a synergistic interaction with SIRT1.

Serum Sirtuin-1, HMGB1-TLR4, NF-KB and IL-6 Levels in Alzheimer's: The Relation Between Neuroinflammatory Pathway and Severity of Dementia.

In this study, serum Sirtuin-1(SIRT-1), High Mobility Group Box 1 (HMGB1), Toll-Like Receptor-4 (TLR4), Nuclear Factor Kappa B (NF-kB), Interleukin-6 (IL-6), Amyloid βeta-42 (Aβ- 42), and p-tau181 levels in patients diagnosed with AD according to NINCS-ADRA criteria were studied. We investigated the inflammatory pathways that lead to progressive neuronal loss and highlight their possible relationship with dementia severity in the systemic circulation. Patients over 60 years of age were grouped according to their Standard Mini Mental Test results, MRI, and/or Fludeoxyglucose positron emission tomography or according to their CT findings as Control n:20; AD n:32; Vascular Dementia (VD) n:17; AD + VD; n = 21. Complete blood count, Glucose, Vitamin B12, Folic Acid, Enzymes, Urea, Creatinine, Electrolytes, Bilirubin, and Thyroid Function tests were evaluated. ELISA was used for the analysis of serum SIRT1, HMGB1, TLR4, NF-kB, IL-6, Aβ-42, and p-tau181 levels. Levels of serum Aβ-42, SIRT1, HMGB1, and IL-6 were significantly higher (p< 0.001, p< 0.01, p< 0.001, and p< 0.001, respectively), and TLR4 levels were significantly lower (p< 0.001) in the dementia group than in the control group. No significant difference was observed between dementia and control groups for serum NF-kB and p-tau181 levels. Our results show that the levels of the Aβ42, SIRT 1, HMGB1, and TLR4 pathways are altered in AD and VD. SIRT 1 activity plays an important role in the inflammatory pathway of dementia development, particularly in AD.