EPM2AIP1 Immunohistochemistry Is Inadequate as A Surrogate Marker for MLH1 Promoter Hypermethylation Testing in Colorectal Cancer.

MLH1 promoter hypermethylation (MPH) analysis is an essential step in the universal tumor testing algorithm for Lynch syndrome, the most common inherited predisposition to colorectal cancer (CRC). MPH usually indicates sporadic CRC. EPM2AIP1 gene shares the same promoter as MLH1, therefore MPH should also silence EPM2AIP1 transcription leading to loss of protein expression on immunohistochemistry (IHC). It has been previously reported that EPM2AIP1 IHC can be used as a surrogate for MPH in endometrial cancer. Our goal was to evaluate the feasibility of EPM2AIP1 IHC as a surrogate for MPH in CRC. 101 microsatellite instable CRC cases were selected, including 19 cases from whole tumor sections and 82 cases from tissue microarrays. 74 cases were with MPH and 27 without MPH. All 74 cases with MPH showed absent MLH1 by IHC, but only 47 (64%) exhibited loss of expression of EPM2AIP1. Of the 27 cases without MPH, 9 (33%) cases had unexpected loss of EPM2AIP1 expression. Of note, 10 cases were MLH1-mutated Lynch syndrome without MPH, 2 cases showed unexpected loss of EPM2AIP1 staining. Of the 6 cases with double somatic mutations of MLH1 gene (without MPH), only 4 cases demonstrated intact expression of EPM2AIP1 as expected. Taken together, EPM2AIP1 loss was 64% sensitive and 67% specific for MPH, with an accuracy of 64%. We conclude that, unless stain quality improves with different clones or platforms, EPM2AIP1 IHC will likely not be useful as a surrogate test for MPH in CRC.

Activated AMP-protein kinase (pAMPK) is overexpressed in human somatotroph pituitary adenomas.

INTRODUCTION: AMPK (AMP-activated protein kinase) is an enzyme that acts as a metabolic sensor and regulates multiple pathways via phosphorylating proteins in metabolic and proliferative pathways. The aim of this work was to study the activated cellular AMPK (phosphorylated-AMPK at Thr172, pAMPK) levels in pituitary tumor samples from patients with sporadic and familial acromegaly, as well as in samples from normal human pituitary gland. METHODS: We studied pituitary adenoma tissue from patients with sporadic somatotroph adenomas, familial acromegaly with heterozygote germline variants in the aryl hydrocarbon receptor interacting protein (AIP) gene (p.Q164*, p.R304* and p.F269_H275dup) and autopsy from normal pituitary glands without structural alterations. RESULTS: Cellular levels of pAMPK were significantly higher in patients with sporadic acromegaly compared to normal pituitary glands (p < 0.0001). Tissues samples from patients with germline AIP mutations also showed higher cellular levels of pAMPK compared to normal pituitary glands. We did not observe a significant difference in cellular levels of pAMPK according to the cytokeratin (CAM5.2) pattern (sparsely or densely granulated) for tumor samples of sporadic acromegaly. CONCLUSION: Our data show, for the first time in human cells, an increase of cellular levels of pAMPK in sporadic somatotropinomas, regardless of cytokeratin pattern, as well as in GH-secreting adenomas from patients with germline AIP mutations.

Atherogenic index of plasma: a new indicator for assessing the short-term mortality of patients with acute decompensated heart failure.

Objective: Arteriosclerosis is a primary causative factor in cardiovascular diseases. This study aims to explore the correlation between the atherogenic index of plasma (AIP) and the 30-day mortality rate in patients with acute decompensated heart failure (ADHF). Methods: A total of 1,248 ADHF patients recruited from the Jiangxi-Acute Decompensated Heart Failure1 (JX-ADHF1) cohort between 2019 and 2022 were selected for this study. The primary outcome was the 30-day mortality rate. Multivariable Cox regression, restricted cubic splines (RCS), and stratified analyses were utilized to assess the relationship between AIP and the 30-day mortality rate in ADHF patients. Mediation models were employed for exploratory analysis of the roles of inflammation, oxidative stress, and nutrition in the association between AIP and the 30-day mortality rate in ADHF patients. Results: During the 30-day follow-up, 42 (3.37%) of the ADHF patients died. The mortality rates corresponding to the quartiles of AIP were as follows: Q1: 1.28%, Q2: 2.88%, Q3: 2.88%, Q4: 6.41%. The multivariable Cox regression revealed a positive correlation between high AIP and the 30-day mortality rate in ADHF patients [Hazard ratio (HR) 3.94, 95% confidence interval (CI): 1.08-14.28], independent of age, gender, heart failure type, cardiac function classification, and comorbidities. It is important to note that there was a U-shaped curve association between AIP (<0.24) and the 30-day mortality rate before the fourth quartile, with the lowest 30-day mortality risk in ADHF patients around an AIP of -0.1. Furthermore, mediation analysis suggested significant mediating effects of inflammation and nutrition on the 30-day mortality rate in ADHF patients related to AIP, with inflammation accounting for approximately 24.29% and nutrition for about 8.16% of the mediation effect. Conclusion: This retrospective cohort analysis reveals for the first time the association between AIP and the 30-day mortality rate in ADHF patients. According to our findings, maintaining an AIP around -0.1 in ADHF patients could be crucial for improving poor prognoses from a medical perspective. Additionally, for ADHF patients with high AIP, it is important to assess and, if necessary, enhance nutritional support and anti-inflammatory treatment.

Relationship between atherosclerotic burden and depressive symptoms in hypertensive patients: A cross-sectional study based on the NHANES database.

OBJECTIVE: The relationship between atherosclerotic burden, depressive symptoms, and clinically relevant depression (CRD) in hypertensive patients is unclear. In this study, we used the atherosclerotic index of plasma (AIP) to quantify atherosclerotic burden and explore its association with depressive symptoms and CRD in hypertensive patients. METHODS: Hypertension-diagnosed patients were extracted from the National Health and Nutrition Examination Survey (NHANES) database. The relationships between AIP and depressive symptoms and CRD risk in patients were examined through the weighted logistic regression and the weighted linear regression models. Restrictive cubic spline curves were employed to analyze potential nonlinear associations between AIP and outcome indicators. Additionally, subgroup analyses and intergroup interaction tests were conducted. RESULTS: The AIP was considerably associated with the severity of depressive symptoms in hypertensive patients, according to the findings of weighted linear regression. Weighted logistic regression analysis showed that high AIP was significantly associated with a high risk of clinically relevant depression in hypertensive patients. This trend was consistent across various subgroups within the population. CONCLUSION: AIP was observed to be a significant risk factor for clinically relevant depression in hypertensive patients. Atherosclerotic burden in hypertensive patients was significantly associated with the severity of their depressive symptoms.

Predicting coronary artery severity in patients undergoing coronary computed tomographic angiography: Insights from pan-immune inflammation value and atherogenic index of plasma.

BACKGROUND AND AIMS: Coronary computed tomographic angiography (CCTA) is pivotal in diagnosing coronary artery disease (CAD). We explored the link between CAD severity and two biomarkers, Pan-Immune Inflammation Value (PIV) and Atherogenic Index of Plasma (AIP), in stable CAD patients. METHODS AND RESULTS: A retrospective observational study of 409 CCTA patients with stable angina pectoris. Logistic regression identified predictors of severe CAD, stratified by CAD-RADS score. Receiver Operating Characteristic (ROC) curves evaluated predictive performance. PIV and AIP were significant predictors of severe CAD (PIV: OR 1.002, 95% CI: 1.000-1.004, p < 0.021; AIP: OR 0.963, 95% CI: 0.934-0.993, p < 0.04). AUC values for predicting severe CAD were 0.563 (p < 0.001) for PIV and 0.625 (p < 0.05) for AIP. Combined with age, AUC improved to 0.662 (p < 0.02). CONCLUSIONS: PIV and AIP were associated with severe CAD, with AIP demonstrating superior predictive capability. Incorporating AIP into risk assessment could enhance CAD prediction, offering a cost-effective and accessible method for identifying individuals at high risk of coronary atherosclerosis.

Gender differences in the association between changes in the atherogenic index of plasma and cardiometabolic diseases: a cohort study.

OBJECTIVE: The relationship between changes in Atherogenic Index of Plasma (AIP) and cardiometabolic diseases (CMD) in middle-aged and elderly individuals remains unclear. This study aims to explore the association between changes in AIP and CMD. METHODS: This study included 3,791 individuals aged over 45 years from CHARLS. Participants were divided into four groups using the K-Means clustering method. Cumulative AIP was used as a quantitative indicator reflecting changes in AIP. Differences in baseline data and CMD incidence rates among these four groups were compared. Multifactorial logistic regression models were used to assess the relationship between changes in AIP and CMD, and subgroup analysis and interaction tests were conducted to evaluate potential relationships between changes in AIP and CMD across different subgroups. Restricted cubic splines (RCS) were used to assess the dose-response relationship between cumulative AIP and CMD. RESULTS: Changes in AIP were independently and positively associated with CMD. In males, the risk significantly increased in class4 compared to class1 (OR 1.75, 95%CI 1.12-2.73). In females, changes in AIP were not significantly associated with CMD. Cumulative AIP was positively correlated with CMD (OR 1.15, 95%CI 1.01-1.30), with significant gender differences in males (OR 1.29, 95%CI 1.07-1.55) and females (OR 1.03, 95%CI 0.87-1.23) (p for interaction = 0.042). In addition, a linear relationship was observed between cumulative AIP and CMD in male. CONCLUSION: Substantial changes in AIP may increase the risk of CMD in middle-aged and elderly Chinese males. Dynamic monitoring of AIP is of significant importance for the prevention and treatment of CMD.

The link between serum neuregulin-1 and atherogenic index in type 2 diabetes mellitus.

BACKGROUND: Neuregulin-1(NRG-1) is a protein that belongs to the group of epidermal growth factors. It plays vital roles in anti-fibrotic effects on the myocardium. The current paper explores the role of NRG-1 in type 2 diabetes mellitus (T2DM) and its relation to atherogenic index as a factor for increasing cardiovascular disease(CVD) risk. MATERIAL AND METHODS: In this study, 79 diabetes mellitus patients are independent insulin. These patients consisted of 53 females and 26 males their age were ranged 40-67 years. They were divided into two groups depending on the atherogenic index of plasma (AIP). Group I including48 diabetic patient with high risk of CVD and group II including 31 diabetic patients without risk CVD. Forty healthy individuals were included as control. RESULT: When compared to the control group, the serum levels of NRG-1 were significantly lower (p = 0.01). Additionally, group I had a much lower NRG-1level than group II. The results of multiple stepwise regression showed that the only independent predictor for NRG-1 level prediction was AIP (ß = - 0.600, P = 0.040). When comparing the diabetic patients with high risk factors for CVD to the healthy subject group, the AUC was outstanding (AUC = 0.889, P = 0.001) and had a high diagnosis. CONCLUSIONS: We proved low NRG-1 levels in diabetic patients and the association of highest NRG-1 amounts to a better AIP. Moreover, the measurement of NRG-1 levels could be beneficial as laboratory markers to monitor for increasing CVD risk in type 2 diabetes mellitus.

Eye Movement Desensitization and Reprocessing (EMDR) treatment in the medical setting: a systematic review.

Background: Literature points towards the potential benefits of the application of Eye Movement and Desensitization Processing (EMDR)-therapy for patients in the medical setting, with cancer and pain being among the domains it is applied to. The field of applying EMDR-therapy for patients treated in the medical setting has evolved to such an extent that it may be challenging to get a comprehensive overview.Objective: This systematic literature review aims to evaluate the use and effectiveness of Eye Movement Desensitization and Reprocessing (EMDR) therapy in patients treated in the medical setting.Methods: We performed a literature search following the PRISMA guidelines. Studies were included if the effectiveness of EMDR-therapy was assessed in adult patients treated in a medical setting. Excluded were patients exclusively suffering from a mental health disorder, without somatic comorbidity. A risk of bias analysis was performed. This review was registered on PROSPERO (CRD42022325238).Results: Eighty-seven studies, of which 26 (pilot)-RCTs were included and categorized in 14 medical domains. Additionally, three studies focusing on persistent physical complaints were included. Most evidence exists for its application in the fields of oncology, pain, and neurology. The overall appraisal of these studies showed at least moderate to high risks of bias. EMDR demonstrated effectiveness in reducing symptoms in 85 out of 87 studies. Notably, the occurrence of adverse events was rarely mentioned.Conclusions: Overall, outcomes seem to show beneficial effects of EMDR on reducing psychological and physical symptoms in patients treated in a medical setting. Due to the heterogeneity of reported outcomes, effect sizes could not be pooled. Due to the high risk of bias of the included studies, our results should be interpreted with caution and further controlled high-quality research is needed.

First overview on the use of EMDR for adult patients treated in the medical setting.EMDR seems beneficial in improving psychological and physical symptoms.Given the heterogeneity of studies and high risk of bias, further controlled studies are needed in this field.

Elevated AIP is associated with the prevalence of MAFLD in the US adults: evidence from NHANES 2017-2018.

Background: Atherogenic Index of plasma (AIP) is closely related to metabolic abnormalities. But as of now, there is no definitive conclusion on the dose-response relationship pattern between AIP and metabolic associated fatty liver disease (MAFLD). Objective: The objective of this study was to provide a fresh insight for understanding the intrinsic link between AIP and the prevalence of MAFLD by exploring the dose-response pattern between AIP and MAFLD. Methods: A total of 9254 participants received the survey and 1090 participants were finally included according to the screening criteria. To evaluate the association between AIP and the prevalence of MAFLD based on weighted multivariate logistic regression. Sensitivity analysis of the association between AIP and MAFLD was performed using propensity score matching (PSM). Restrictive cubic splines (RCS) were used to identify patterns of dose-response relationships between AIP and MAFLD, and receiver operator characteristic (ROC) curves were used to evaluate the predictive ability of AIP and traditional lipid parameters for MAFLD. Results: In this study, a total of 563 participants were found to have MAFLD. The results of weighted multivariate logistic regression analysis demonstrated that, after adjusting for sex and age, participants in the highest quartile (Q4) of AIP had a significantly increased risk of developing MAFLD compared to those in the lowest quartile (Q1) (Model 2: OR = 9.03, 95% CI 4.75-17.17). A similar trend was observed in the fully adjusted model (Model 3: OR = 3.85, 95% CI 1.55-9.52). The RCS analysis revealed a linear dose-response association between AIP and MAFLD(P for crude non-linearity = 0.087). This association remained significant after accounting for potential confounding variables(P for adjusted non-linearity = 0.663). The ROC curve results suggest that AIP performs better than traditional lipid indicators in predicting MAFLD (AUC = 0.732, 95%CI 0.705-0.758). Conclusion: A linear dose-response relationship exists between AIP and MAFLD, suggesting that as AIP increases, so does the risk of developing MAFLD.

Accessing the relationship between six surrogate insulin resistance indexes and the incidence of rapid kidney function decline and the progression to chronic kidney disease among middle-aged and older adults in China: Results from the China health and retirement longitudinal study.

AIMS: Insulin resistance is closely related to kidney function decline, but which insulin resistance index could better predict rapid kidney function decline (RKFD) remains unclear. We aimed to evaluate the prospective association between six insulin resistance indexes: Chinese Visceral Adiposity Index (CVAI), Lipid Accumulation Product (LAP), Atherogenic Index of Plasma (AIP), triglyceride-glucose (TyG) index, triglyceride-glucose × Body Mass Index (TyGBMI) and triglyceride-glucose × waist circumference (TyGWC) with RKFD and further the progression to chronic kidney disease (CKD). METHODS AND MEASUREMENTS: Data were obtained from the China Health and Retirement Longitudinal Study. Participants with normal kidney function (eGFRcr-cys ≥60 ml/min per 1.73 m2) and ≥45 years old were included at the baseline (year 2011). The eGFR was estimated by a combination of serum creatinine and cystatin C. The primary outcome was RKFD, defined as an annualized decline in eGFRcr-cys of 5 ml/min per 1.73 m2 or more. Secondary outcome was progression to CKD under the condition of RKFD, defined as an annualized decline in eGFRcr-cys of 5 ml/min per 1.73 m2 or more combined with eGFRcr-cys <60 ml/min per 1.73 m2 at the exit visit. Logistic analysis was applied for analysis of the association between six insulin resistance indexes and RKFD or progression to CKD. We use receiver operating characteristic curves to study the predictive performance of six insulin resistance indexes. Subgroup analysis were conducted by diabetes or hypertension status of the participants. RESULTS: A total of 3899 participants with normal kidney function were included in this study. After a 3.99 years follow-up, 191 of them ended up with RKFD. Among them, 66 participants progressed to CKD. Logistic analysis showed that per SD increase of all the six insulin resistance indexes were significantly associated with the incidence of RKFD (all P < 0.01), among which, TyGWC had the best predictive value for RKFD. There were significant association between per SD increase of CVAI, LAP, TyGBMI and TyGWC with progression to CKD (all P < 0.01), and CVAI had better predictive role than other indexes. In subgroup analysis, we found that the association between insulin resistance indexes and progression to CKD was more significant in subjects with hypertension or without diabetes. However, no significant differences were observed in the RKFD group. CONCLUSIONS: In this study we proved six insulin resistance indexes were predictively associated with RKFD in Chinese with normal renal function over age 45. TyGWC is the best insulin resistance index for predicting RKFD. CVAI is the best index for predicting further progression to CKD.

Molecular and physiological characterization of AIP1, encoding the acetolactate synthase regulatory subunit in rice.

Flooding deprives plants of oxygen and thereby causes severe stress by interfering with energy production, leading to growth retardation. Enzymes and metabolites may help protect plants from waterlogging and hypoxic environmental conditions. Acetolactate synthase (ALS) is a key enzyme in the biosynthesis of branched-chain amino acids (BCAAs), providing the building blocks for proteins and various secondary metabolites. Additionally, under energy-poor conditions, free BCAAs can be used as an alternative energy source by mitochondria through a catabolic enzyme chain reaction. In this study, we characterized ALS-INTERACTING PROTEIN 1 (OsAIP1), which encodes the regulatory subunit of ALS in rice (Oryza sativa). This gene was expressed in all parts of the rice plant, and its expression level was significantly higher in submerged and low-oxygen environments. Rice transformants overexpressing OsAIP1 showed a higher survival rate under hypoxic stress than did non-transgenic control plants under the same conditions. The OsAIP1-overexpressing plants accumulated increased levels of BCAAs, demonstrating that OsAIP1 is an important factor in the hypoxia resistance mechanism. These results suggest that ALS proteins are part of a defense mechanism that improves the tolerance of plants to low-oxygen environments.

An ex vivo Approach in European Seabass Leucocytes Supports the in vitro Regulation by Postbiotics of Aip56 Gene Expression of Photobacterium damselae subsp. piscicida.

Shewanella putrefaciens Pdp11 (SpPdp11) is a probiotic strain assayed in aquaculture; however, its postbiotic potential is unknown. Postbiotics are bacterial metabolites, including extracellular products (ECPs) that improve host physiology and immunity. Their production and composition can be affected by different factors such as the growing conditions of the probiotics. Photobacterium damselae subsp. piscicida strain Lg 41/01 (Phdp) is one of the most important pathogens in marine aquaculture. The major virulent factor of this bacterium is the exotoxin aip56, responsible for inducing apoptosis of fish leucocytes. Viable SpPdp11 cells have been reported to increase resistance to challenges with Phdp. This work aimed to evaluate the effect of two ECPs, T2348-ECP and FM1548-ECP, obtained from SpPdp11 grown under different culture conditions that previously demonstrated to exert different degradative and non-cytotoxic activities, as well as the effect on pathogens biofilm formation. These SpPdp11-ECPs were then analyzed by their effect on the viability, phagocytosis, respiratory burst and apoptogenic activity against European sea bass leucocytes infected or not with Phdp supernatant. Both ECPs, T2348-ECP and FM1548-ECP, were not cytotoxic against leucocytes and significantly reduced their apoptosis. Phagocytosis and respiratory burst of leucocytes were significantly reduced by incubation with Phdp supernatant, and not influenced by incubation with T2348-ECP or FM1548-ECP. However, both activities were significantly increased after leucocyte incubation with combined T2348-ECP and FM1548-ECP with Phdp supernatant, compared to those incubated only with Phdp supernatant. Finally, both T2348-ECP and FM1548-ECP significantly reduced the relative in vitro expression of the Phdp aip56 encoding gene.

The Effect of Maternal Overweight/Obesity on Serum and Breastmilk Leptin, and Its Associations with Body Composition, Cardiometabolic Health Indices, and Maternal Diet: The BLOOM Study.

In overweight and obese patients, elevated serum and breastmilk leptin concentrations are observed, with serum leptin also being likely affected by the diet. We analyzed serum and breastmilk leptin in normal weight (NW) and overweight/obese (OW/OB) mothers, and evaluated its associations with (1) maternal anthropometric parameters; (2) markers of cardiometabolic health; and (3) the maternal diet. The BLOOM (Breastmilk and the Link to Overweight/Obesity and Maternal diet) study was conducted among 40 women (n = 20 OW/OB; n = 20, NW) who were exclusively or predominantly breastfeeding for 15.5 ± 1.2 (OW/OB group (0.99)) weeks. We collected 24 h breastmilk and fasting blood samples for leptin analysis by ELISA. Maternal dietary habits were evaluated using a 3-day dietary record and food frequency questionnaire, which were used to calculate the Polish-adapted Mediterranean Diet score. Maternal anthropometric measurements and DEXA scans were performed, and anthropometric and cardiometabolic indices were calculated. The OW mothers had 1.4 times higher serum levels, while OB mothers had 4.5 and 6.2 higher serum and breastmilk leptin levels, respectively, in comparison to the NW mothers. The FM% was correlated with serum and breastmilk leptin levels (r = 0.878, r = 0.638). Serum leptin was associated with markers of cardiometabolic health such as AIP, CMI, and VAI in the NW mothers, and with LAP in the OW/OB mothers. Higher energy, fructose intake and adherence to the Mediterranean diet were associated with serum leptin in the NW mothers (ß = 0.323, 0.039-0.608; ß = 0.318, 0.065-0.572; ß = 0.279, 0.031-0.528); meanwhile, higher adherence to the Mediterranean diet could protect against elevated breastmilk leptin concentrations in OW/OB mothers (ß = -0.444, -0.839--0.050), even after adjustment for FM%. Our results suggest a potential association between maternal serum leptin concentrations and cardiometabolic health. In addition, we confirm the importance of healthy dietary patterns in the improvement of breastmilk composition.

The association of atherogenic index of plasma with cardiovascular outcomes in patients with coronary artery disease: A systematic review and meta-analysis.

BACKGROUND: Atherogenic index of plasma (AIP) represents a novel marker in the current era of cardiovascular diseases. In this meta-analysis, we aimed to evaluate the association of AIP with cardiovascular prognosis in patients with coronary artery disease (CAD). METHODS: PubMed, Scopus, and Web of Science databases were searched from inception through 2024. The primary outcome was major cardiovascular events (MACE). The secondary outcomes included all-causes death, cardiovascular death, myocardial infarction (MI), stroke, revascularization, and no-reflow phenomenon. AIP was determined by taking the logarithm of the ratio of triglyceride (TG) to high-density lipoprotein cholesterol (HDL-C). The data analysis was represented using the risk ratio (RR) along with a 95% confidence interval (CI). RESULTS: Sixteen studies with a total number of 20,833 patients met the eligible criteria. The pooled-analysis showed a significant increased risk of MACE in the highest AIP group compared with the lowest AIP group (RR = 1.63; 95% CI, 1.44-1.85; P < 0.001). A similar result was observed when AIP was regarded as a continuous variable (RR = 1.54; 95% CI, 1.30-1.83; P < 0.001). Besides, elevated AIP was associated with increased risk of cardiovascular death (RR = 1.79; 95% CI, 1.09-2.78; P = 0.02), MI (RR = 2.21; 95% CI, 1.55-3.13; P < 0.001), revascularization (RR = 1.62; 95% CI, 1.34-1.97; P < 0.001), no-reflow phenomenon (RR = 3.12 95% CI, 1.09-8.96; P = 0.034), and stent thrombosis (RR = 13.46; 95%CI, 1.39-129.02; P = 0.025). However, AIP was not significantly associated with the risk of all-causes death and stroke among patients with CAD. CONCLUSIONS: The results of this study demonstrated that increased AIP is an independent prognostic factors in patients with CAD. Further research is warranted to elucidate the potential development of targeted interventions to modify AIP levels and improve patient outcomes.

Using new indices to predict metabolism dysfunction-associated fatty liver disease (MAFLD): analysis of the national health and nutrition examination survey database.

BACKGROUND: Metabolism dysfunction-associated fatty liver disease (MAFLD), is the most common chronic liver disease. Few MAFLD predictions are simple and accurate. We examined the predictive performance of the albumin-to-glutamyl transpeptidase ratio (AGTR), plasma atherogenicity index (AIP), and serum uric acid to high-density lipoprotein cholesterol ratio (UHR) for MAFLD to design practical, inexpensive, and reliable models. METHODS: The National Health and Nutrition Examination Survey (NHANES) 2007-2016 cycle dataset, which contained 12,654 participants, was filtered and randomly separated into internal validation and training sets. This study examined the relationships of the AGTR and AIP with MAFLD using binary multifactor logistic regression. We then created a MAFLD predictive model using the training dataset and validated the predictive model performance with the 2017-2018 NHANES and internal datasets. RESULTS: In the total population, the predictive ability (AUC) of the AIP, AGTR, UHR, and the combination of all three for MAFLD showed in the following order: 0.749, 0.773, 0.728 and 0.824. Further subgroup analysis showed that the AGTR (AUC1 = 0.796; AUC2 = 0.690) and the combination of the three measures (AUC1 = 0.863; AUC2 = 0.766) better predicted MAFLD in nondiabetic patients. Joint prediction outperformed the individual measures in predicting MAFLD in the subgroups. Additionally, the model better predicted female MAFLD. Adding waist circumference and or BMI to this model improves predictive performance. CONCLUSION: Our study showed that the AGTR, AIP, and UHR had strong MAFLD predictive value, and their combination can increase MAFLD predictive performance. They also performed better in females.

Exploring the Role of Serum Osteonectin and Hsp27 in Pediatric MAFLD Diagnosis and Cardiometabolic Health.

BACKGROUND: Childhood obesity is one of the major challenges of public health policies. The problem of fatty liver in childhood, known as MAFLD (metabolic dysfunction-associated fatty liver disease), is of particular interest as the gold standard diagnosis technique is invasive (liver biopsy). Hence, efforts are made to discover more specific biomarkers for the MAFLD signature. Therefore, the aim of the study was to evaluate Osteonectin and Hsp27 as biomarkers for MAFLD diagnosis and to assess their links with auxological and biochemical profiles of overweight and obese pediatric subjects. METHODS: A cross-sectional study in which we (re)analyzed data from the MR PONy cohort comprising 71 pediatric subjects. Auxological data, liver ultrasonography and biochemical serum profile were recorded. Lipid-derived indices and body composition indices were calculated. Nevertheless, serum Osteonectin and Hsp27 levels were assessed using an ELISA approach. RESULTS: MAFLD prevalence was 40.8%. Higher Osteonectin levels were noted in MAFLD subjects versus non-MAFLD subjects and in dyslipidemic children regardless of their liver function status. Lipid-derived indices had good diagnostic capacity for MAFLD. CONCLUSIONS: We confirm Osteonectin as a MAFLD diagnosis biomarker in children. Also, lipid-derived indices are useful as metabolic-associated organ impairment markers in children even before the onset of obesity.

The aryl hydrocarbon receptor-interacting protein in cancer and immunity: Beyond a chaperone protein for the dioxin receptor.

The aryl hydrocarbon receptor (AhR)-interacting protein (AIP) is a ubiquitously expressed, immunophilin-like protein best known for its role as a co-chaperone in the AhR-AIP-Hsp90 cytoplasmic complex. In addition to regulating AhR and the xenobiotic response, AIP has been linked to various aspects of cancer and immunity that will be the focus of this review article. Loss-of-function AIP mutations are associated with pituitary adenomas, suggesting that AIP acts as a tumor suppressor in the pituitary gland. However, the tumor suppressor mechanisms of AIP remain unclear, and AIP can exert oncogenic functions in other tissues. While global deletion of AIP in mice yields embryonically lethal cardiac malformations, heterozygote, and tissue-specific conditional AIP knockout mice have revealed various physiological roles of AIP. Emerging studies have established the regulatory roles of AIP in both innate and adaptive immunity. AIP interacts with and inhibits the nuclear translocation of the transcription factor IRF7 to inhibit type I interferon production. AIP also interacts with the CARMA1-BCL10-MALT1 complex in T cells to enhance IKK/NF-κB signaling and T cell activation. Taken together, AIP has diverse functions that vary considerably depending on the client protein, the tissue, and the species.

Case report: Complete restoration of the HPA axis function in Cushing's disease with drug treatment.

This report describes a rare case of a 20-year-old man with an ACTH- and prolactin-secreting invasive pituitary macroadenoma causing hyperprolactinemia and Cushing's disease. He was later found to have an AIP mutation. Treatment with cabergoline (1.5 mg weekly) normalized prolactin concentrations and induced a major shrinkage of the adenoma. Not only was urinary free cortisol normalized for more than 14 years, but also the treatment induced normal hypothalamo-pituitary-adrenal (HPA) axis function as illustrated by the reappearance of a normal cortisol/ACTH circadian rhythm, cortisol suppression to dexamethasone, and disappearance of the excessive and aberrant responses to CRH and desmopressin, respectively. This case is the first description of complete restoration of the physiological characteristics of the HPA axis by a medication during the treatment of Cushing's disease. Although exceptional, it illustrates that drugs targeting the pituitary adenoma can bring true complete remission of Cushing's disease.

The association between the AIP and undiagnosed diabetes in ACS patients with different body mass indexes and LDL-C levels: findings from the CCC-ACS project.

BACKGROUND: The atherogenic index of plasma (AIP) has been demonstrated to be significantly associated with the incidence of prediabetes and diabetes. This study aimed to investigate the association between the AIP and undiagnosed diabetes in acute coronary syndrome (ACS) patients. METHODS: Among 113,650 ACS patients treated with coronary angiography at 240 hospitals in the Improving Care for Cardiovascular Disease in China-ACS Project from 2014 to 2019, 11,221 patients with available clinical and surgical information were included. We analyzed these patients' clinical characteristics after stratification according to AIP tertiles, body mass index (BMI) and low-density lipoprotein cholesterol (LDL-C) levels. RESULTS: The AIP was independently associated with a greater incidence of undiagnosed diabetes. The undiagnosed diabetes was significantly greater in the T3 group than in the T1 group after adjustment for confounders [T3 OR 1.533 (1.199-1.959) p < 0.001]. This relationship was consistent within normal weight patients and patients with an LDL-C level ≥ 1.8 mmol/L. In overweight and obese patients, the AIP was significantly associated with the incidence of undiagnosed diabetes as a continuous variable after adjustment for age, sex, and BMI but not as a categorical variable. The area under the receiver operating characteristic curve (AUC) of the AIP score, triglyceride (TG) concentration, and HDL-C concentration was 0.601 (0.581-0.622; p < 0.001), 0.624 (0.603-0.645; p < 0.001), and 0.493 (0.472-0.514; p = 0.524), respectively. A nonlinear association was found between the AIP and the incidence of undiagnosed diabetes in ACS patients (p for nonlinearity < 0.001), and this trend remained consistent between males and females. The AIP may be a negative biomarker associated with undiagnosed diabetes ranging from 0.176 to 0.738. CONCLUSION: The AIP was significantly associated with the incidence of undiagnosed diabetes in ACS patients, especially in those with normal weight or an LDL-C level ≥ 1.8 mmol/L. A nonlinear relationship was found between the AIP and the incidence of undiagnosed diabetes, and this trend was consistent between male and female patients. The AIP may be a negative biomarker associated with undiagnosed diabetes and ranges from 0.176 to 0.738.

Association between atherogenic index of plasma control level and incident cardiovascular disease in middle-aged and elderly Chinese individuals with abnormal glucose metabolism.

BACKGROUND: The atherogenic index of plasma (AIP) and cardiovascular disease (CVD) in participants with abnormal glucose metabolism have been linked in previous studies. However, it was unclear whether AIP control level affects the further CVD incidence among with diabetes and pre-diabetes. Therefore, our study aimed to investigate the association between AIP control level with risk of CVD in individuals with abnormal glucose metabolism. METHODS: Participants with abnormal glucose metabolism were included from the China Health and Retirement Longitudinal Study. CVD was defined as self-reporting heart disease and/or stroke. Using k-means clustering analysis, AIP control level, which was the log-transformed ratio of triglyceride to high-density lipoprotein cholesterol in molar concentration, was divided into five classes. The association between AIP control level and incident CVD among individuals with abnormal glucose metabolism was investigated multivariable logistic regression analysis and application of restricted cubic spline analysis. RESULTS: 398 (14.97%) of 2,659 participants eventually progressed to CVD within 3 years. After adjusting for various confounding factors, comparing to class 1 with the best control of the AIP, the OR for class 2 with good control was 1.31 (95% CI, 0.90-1.90), the OR for class 3 with moderate control was 1.38 (95% CI, 0.99-1.93), the OR for class 4 with worse control was 1.46 (95% CI, 1.01-2.10), and the OR for class 5 with consistently high levels was 1.56 (95% CI, 1.03-2.37). In restricted cubic spline regression, the relationship between cumulative AIP index and CVD is linear. Further subgroup analysis demonstrated that the similar results were observed in the individuals with agricultural Hukou, history of smoking, diastolic blood pressure ≥ 80mmHg, and normal body mass index. In addition, there was no interaction between the AIP control level and the subgroup variables. CONCLUSIONS: In middle-aged and elderly participants with abnormal glucose metabolism, constant higher AIP with worst control may have a higher incidence of CVD. Monitoring long-term AIP change will contribute to early identification of high risk of CVD among individuals with abnormal glucose metabolism.