Binding Protein Levels Research Articles

The Effects of a Novel Astragalus-Based Extract (Keyfobell Powder (KFB)) on Longitudinal Bone Growth via IGF-1 Upregulation: A Potential Growth Hormone Alternative

Background/Objectives: This study evaluated the effects of a novel Astragalus extract (Keyfobell powder [KFB]) composed of Astragalus membranaceus, red ginseng (Panax ginseng C. A. Meyer), and Cervi Parvum Cornu as a potential growth hormone (GH) alternative. The primary focus was placed on its impact on longitudinal bone growth through the upregulation of circulatory insulin-like growth factor (IGF)-1. Methods: We performed in vitro and in vivo experiments using a hypothalamic cell line and Sprague–Dawley (SD) rats. Quantitative RT-PCR was performed to determine growth hormone-releasing hormone (GHRH) and ghrelin mRNA expressions in GT1-7 cells. The treatment groups were administered KFB at various dosages, and the positive controls received recombinant human GH. Body weight, bone length, and density were assessed, along with serum levels of insulin-like growth factor binding protein (IGFBP)-3 and IGF-1. Results: KFB and somatropin exhibited no cytotoxic effect in GT1-7 cells and increased GHRH and ghrelin mRNA levels in a dose-dependent manner. KFB administration resulted in a significant dose-dependent increase in body weight and bone growth (femur and tibia). Changes in IGF-1 and IGFBP-3 levels were comparable to those observed in the GH-treated group. Based on network pharmacological analysis, multiple compounds in KFB ((20S)-20-hydroxypregn-4-en-3-one, 2-isopropyl-3-methoxypyrazine, caproic acid, daidzein, furfuryl alcohol, lauric acid, octanal, and salicylic acid) may synergistically regulate the PI3K-Akt, Ras, and Rap1 signaling pathways linked to growth control and cartilage formation, leading to a possible increase in height. Conclusions: Our results suggest that KFB can function as a GH-mimetic agent that promotes bone growth through IGF-1 upregulation.

Histone lysine crotonylation associated epigenetic mechanism dynamically regulates prenatal stress induced anxiety-related behaviour in adolescent offspring.

This study designed to examine whether social/ environmental experiences can induce the epigenetic modification, and influence the associated physiology and behaviour. To test this, we have used social stress [prenatal stress (PNS)] model and then housed at environmental enrichment (EE) condition to evaluate the interaction between specific epigenetic modification and its influence on behaviour. Pregnant rats were randomly divided into a control group, PNS group, and PNS+EE group. PNS and PNS+EE animals were subjected to social defeat (SD) stress during their gestational day (GD) 16-18. PNS animals and their offspring were always housed in standard laboratory condition, PNS+EE animal was housed in EE cage during GD-10 to the pup's age of postnatal day (PND) 30. Animals were tested for anxiety-like behaviour using Open-Field Test (OFT) and memory was examined by passive avoidance test. Western blotting was used to detect the expression pattern of molecules associated with histone crotonylation. We observed anxiety-like behaviour, memory deficit in the animals experienced PNS. Further, level of Methyl-CpG Binding Protein 2 (MeCP2), repressor element-1 silencing transcription factor (REST), Sirtuin 1(SIRT1), Chromodomain Y-like (CDYL) and Enhancer of Zeste 2 Polycomb Repressive Complex 2 Subunit (EZH2) and histone methylation (H3K27me3) was elevated. Where as, the expression of p300, histone crotonylation (H3K18Cr) and neuropeptide VGF were suppressed. Notably, EE restore the normal expression pattern of MeCP2, REST, P300, SIRT1, CYDL, EZH2, H3K27me3, H3K18Cr and VGF. EE reverse the PNS induced alterations, including suppression of histone crotonylation (H3K18Cr), which possibly involved in the regulation of expression of VGF and behaviour.

Diffuse large B-cell lymphoma cell-derived exosomal NSUN2 stabilizes PDL1 to promote tumor immune escape and M2 macrophage polarization in a YBX1-dependent manner.

Diffuse large B-cell lymphoma (DLBCL) is a prevalent and aggressive form of non-Hodgkin's lymphoma with a complex etiology. NOP2/Sun domain 2 (NSUN2) is an RNA methyltransferase that has been linked to the regulation of gene expression in various cancers. However, the function of NSUN2 in DLBCL, specifically its contribution to exosome-driven tumor progression, remains to be thoroughly elucidated. Quantitative real-time polymerase chain reaction was used to analyze the expression of NSUN2 and programmed death ligand 1 variant (PDL1). Western blotting assay was performed to detect the protein levels of NSUN2, PDL1 and Y-box binding protein 1 (YBX1). Cell proliferation was analyzed by cell counting kit-8 and 5-Ethynyl-2'-deoxyuridine assays. Cell apoptosis and CD206-positive cells were quantified by flow cytometry. The levels of tumor necrosis factor-alpha and interferon-γ in cell supernatant were analyzed by enzyme-linked immunosorbent assays. m6A RNA immunoprecipitation and RNA pull-down assays were performed to determine the association between NSUN2 and PDL1. An RNA immunoprecipitation assay was used to analyze the association of YBX1 and PDL1. In vitro findings were validated in a mouse model. NSUN2 was overexpressed in DLBCL tissues and cells. DLBCL cell-derived exosomes facilitated the transfer of NSUN2 to DLBCL cells, which in turn promoted tumor cell proliferation, M2 macrophage polarization, and immune escape and inhibited cell apoptosis. In addition, NSUN2 stabilized PDL1 mRNA through an m5C-dependent mechanism and a YBX1-dependent pathway. Moreover, the suppression of PDL1 significantly mitigated the effects induced by NSUN2 within DLBCL cell-derived exosomes on cellular proliferation, apoptosis, M2 macrophage polarization, and immune evasion. Further, DLBCL cell-derived exosomal NSUN2 promoted tumor growth by regulating PDL1. NSUN2 in DLBCL cell-derived exosomes stabilized PDL1 in a YBX1-dependent manner and thus promoted tumor immune escape and M2 macrophage polarization. These findings highlight the potential of targeting the NSUN2-PDL1 axis as a novel therapeutic strategy for DLBCL.

Obesity Is Associated With Higher Levels of Circulating Cytokines Involved in the Development of Cardiovascular Disease in People Living With HIV.

Obesity is increasingly described in people living with HIV (PLWH), but its impact on immune activation and inflammation in HIV is still poorly characterized. We aimed to analyze the difference in circulating cytokines involved in pathways associated with comorbidities in PLWH according to the presence or absence of obesity. Age- and sex-matched PLWH with and without obesity (body mass index ≥30 kg/m 2 ) from a multicenter, prospective cohort were recruited with a 1:2 ratio. Twenty-three biomarkers covering pathways associated with systemic inflammation (high sensitivity C-Reactive Protein [hsCRP], interleukin (IL)-2, IL-6, tumor necrosis factor receptor-1, tumor necrosis factor receptor-2, tumor necrosis factor-alpha, interferon-gamma, IL-18), coagulation (von Willebrand Factor [vWF], D-dimer, soluble CD40 ligand), endothelial function (E-selectin, P-selectin, soluble intracellular adhesion molecule-1, soluble vascular cell adhesion molecule-1), atherosclerosis (myeloperoxidase [MPO], lipoprotein-associated phospholipase A2), immune regulation (IL-1 receptor antagonist [IL-1RA]), innate immune activation (macrophage inflammatory protein-1, monocyte chemoattractant protein-1, soluble CD163, soluble CD14), and microbial translocation (lipopolysaccharide binding protein) were measured in the 2 groups. Between-group difference in biomarkers were assessed using Mann-Whitney test. Associations between obesity and biomarkers were assessed using logistic regression adjusted for age, sex, ethnicity, smoking status, and antiretroviral therapy. Ninety-nine antiretroviral therapy-treated PLWH were included in the analysis (33 with obesity, 66 without obesity). PLWH with obesity had higher levels of hsCRP, IL-6, vWF, D-dimer, E-selectin, MPO, IL-1RA, and lipopolysaccharide binding protein. Six markers (hsCRP, IL-6, vWF, E-selectin, MPO, IL-1RA), reflecting systemic inflammation, coagulation, and atherosclerosis pathways, were associated with increased odds of obesity in the adjusted logistic regression model: hsCRP (adjusted odds ratio 2.7, 95% CI: [1.7 to 4.29]), IL-6 (3.77 [1.43-9.93]), vWF (5.33 [1.51-18.75]), E-selectin (6.28 [1.36-29.04]), MPO (6.85 [1.87-25.04]), and IL-1RA (6.45 [2.28-18.2]). No association was observed between obesity and markers of innate immune activation and gut microbial translocation. Obesity in PLWH was associated with activation of systemic inflammatory, endothelial, atherosclerosis, and coagulation pathways, rather than those associated with innate immune activation and gut microbial translocation. These pathways point toward an unfavorable cardiovascular profile in PLWH with obesity, which will have to be further explored in future studies on long-term outcomes.

Study of serum Fatty Acid Binding Protein-1 levels in Diabetic Kidney Disease

Study of serum Fatty Acid Binding Protein-1 levels in Diabetic Kidney Disease

Levels of parathyroid hormone and IGF binding protein 1 and associations with mortality and hip fractures in older women

In this study we examined the effect of simultaneously elevated levels of parathyroid hormone (PTH) (≥ 65 ng/mL) and high levels of insulin-like growth factor-binding protein 1 (IGFBP-1) on the 10-year risk of all-cause mortality and hip fractures. Blood tests for levels of PTH and IGFBP-1 was collected at baseline in 338 community-dwelling women in Stockholm aged between 69 and 79 years. Data on hip fractures and all-cause mortality over the next 10 years were retrieved from healthcare registers. The participants were divided into four groups depending on their levels of PTH and IGFBP-1: (A) normal PTH and low IGFBP-1; (B) normal PTH and high IGFBP-1; (C) elevated PTH and low IGFBP-1; (D) elevated PTH and high IGFBP-1. Group D was used as reference. Cox proportional hazard regression (HR) model was used to compare age-adjusted association with hip fractures and all-cause mortality of the four groups. The group with elevated levels of PTH and high IGFBP-1 had a two to three times higher risk of all-cause mortality compared to the other groups but we found no association with hip fractures.

Exposure to Radiofrequency Electromagnetic Fields Enhances Melanin Synthesis by Activating the P53 Signaling Pathway in Mel-Ab Melanocytes.

The skin is the largest body organ that can be physiologically affected by exposure to radiofrequency electromagnetic fields (RF-EMFs). We investigated the effect of RF-EMFs on melanogenesis; Mel-Ab melanocytes were exposed to 1760 MHz radiation with a specific absorption rate of 4.0 W/kg for 4 h/day over 4 days. Exposure to the RF-EMF led to skin pigmentation, with a significant increase in melanin production in Mel-Ab melanocytes. The phosphorylation level of cAMP response element binding protein (CREB) and the expression of microphthalmia-associated transcription factor (MITF), which regulate the expression of tyrosinase, were significantly increased in Mel-Ab after RF-EMF exposure. Interestingly, the expression of tyrosinase was significantly increased, but tyrosinase activity was unchanged in the RF-EMF-exposed Mel-Ab cells. Additionally, the expression of p53 and melanocortin 1 receptor (MC1R), which regulate MITF expression, was significantly increased. These results suggest that the RF-EMF induces melanogenesis by increasing phospho-CREB and MITF activity. Importantly, when Mel-Ab cells were incubated at 38 °C, the melanin production and the levels of tyrosinase significantly decreased, indicating that the increase in melanin synthesis by RF-EMF exposure is not due to a thermal effect. In conclusion, RF-EMF exposure induces melanogenesis in Mel-Ab cells through the increased expression of tyrosinase via the activation of MITF or the phosphorylation of CREB, which are initiated by the activation of p53 and MC1R.

Olaparib promotes FABP4 expression and reduces antitumor effect in ovarian cancer cells with a BRCA1 mutation.

Olaparib (AZD2281) is used as a first-line maintenance treatment for patients with ovarian cancer (OC) with a breast cancer susceptibility gene (BRCA) mutation. Fatty acid binding protein 4 (FABP4) may serve an important role in cancer, but its role in olaparib-treated OC with a BRCA mutation requires further clarification. To explore the function of FABP4 and enhance the efficacy of AZD2281 in OC, cell counting kit-8, cell apoptosis, cell cycle, colony formation, cell transfection, western blotting, reverse transcription-quantitative polymerase chain reaction, chromatin immunoprecipitation, seahorse and reactive oxygen species assays were performed. In the present study, AZD2281 significantly promoted cell apoptosis, and inhibited cell cycle progression and colony formation in COV362 cells. In addition, AZD2281 significantly upregulated the levels of CCAAT enhancer binding protein α (CEBPα), peroxisome proliferator activated receptor γ (PPARγ) and FABP4. AZD2281 markedly promoted fold enrichment of CEBPα in the promoters of PPARγ and FABP4. Furthermore, FABP4 overexpression significantly decreased cell apoptosis and promoted cell cycle progression and colony formation. In contrast, FABP4 knockdown demonstrated the opposite effects. In addition, FABP4 significantly regulated levels of reactive oxygen species, adenosine triphosphate, aerobic glycolysis, basal respiration rate and fatty acid oxidation. The combination of AZD2281 with the FABP4 inhibitor BM S309403 further significantly increased cell apoptosis and decreased colony formation. In conclusion, the findings of the present study demonstrated that AZD2281 significantly enhanced FABP4 expression, leading to diminished antitumor efficacy in OC cells with a BRCA mutation by regulating CEBPα-PPARγ. Conversely, the combination of AZD2281 and FABP4 inhibitor BM S309403 demonstrated heightened antitumor effectiveness, presenting a promising therapeutic strategy for treating patients with OC with a BRCA mutation.

Intestinal fatty acid binding protein is associated with coronary artery disease in long-term type 1 diabetes—the Dialong study

BackgroundIndividuals with type 1 diabetes are at increased risk of accelerated atherosclerosis, causing coronary artery disease (CAD). The underlying mechanisms remain unclear, but new theories proposed are damage of gut mucosa causing leakage and translocation of gut microbiota products into the circulation, leading to inflammatory responses and atherosclerosis. We therefore aimed to study the associations between gut related inflammatory biomarkers and coronary atherosclerosis in individuals with long-term type 1 diabetes.MethodsIn this cross-sectional, controlled study of 102 participants with type 1 diabetes and 63 control subjects, we measured circulating levels of intestinal fatty acid binding protein (I-FABP), soluble cluster of differentiation 14 (sCD14), lipopolysaccharide binding protein (LBP) and interleukin 18 (IL-18) by enzyme-linked immunosorbent assay (ELISA), and further gene expression of CD14 and toll-like receptor 4 (TLR4) by real time PCR in circulating leukocytes and peripheral blood mononuclear cells (PBMCs). The participants had either established coronary heart disease (CHD) or underwent computed tomography coronary angiography (CTCA) to assess for coronary atherosclerosis, including total, calcified and soft/mixed plaque volumes.ResultsIn the diabetes group, the levels of I-FABP were significantly higher in participants with established CHD or significant stenosis on CTCA compared to the participants with normal arteries or non-significant stenosis, with median 1.67 ng/ml (interquartile range [IQR] 1.02–2.32) vs. median 1.09 ng/ml (IQR 0.82–1.58), p = 0.003. I-FABP was associated with significant coronary artery stenosis by CTCA (> 50%) or previously established CHD in the adjusted analysis (odds ratio [OR] = 2.32, 95% confidence interval [CI]: 1.09–4.95; p = 0.029). The levels of I-FABP correlated also to total coronary plaque volume (r = 0.22, p < 0.05). This association remained significant after adjusting for age, sex, persistent albuminuria, eGFR, statin treatment, diabetes duration and mean time-weighted variables; HbA1c, LDL-cholesterol and systolic blood pressure (OR = 1.97, 95% CI: 1.28–3.01; p = 0.002).ConclusionsIn this cohort of individuals with long-term type 1 diabetes I-FABP associated significantly with coronary artery stenosis, suggesting a potential role of gut mucosa damage in the process of atherosclerosis in type 1 diabetes.

Longitudinal analysis of urinary I-FABP in extremely preterm infants that develop necrotizing enterocolitis.

Intestinal fatty acid binding protein (I-FABP) is an intestinal epithelial protein detectable in infants with necrotizing enterocolitis (NEC). The longitudinal behavior of I-FABP following NEC or its association with gastrointestinal or neurodevelopmental outcomes is unknown. In this secondary analysis of the Preterm Erythropoietin Neuroprotection Trial, we compared infants with and without NEC. Urine I-FABP concentrations in matched infants (n = 70) were measured serially using ELISA and compared using paired analysis. In infants with NEC, the associations of I-FABP levels with short-term outcomes and neurodevelopmental outcomes at 22-26 months corrected age were determined using non-parametric analysis. Infants with NEC were more likely to have cholestasis, death or severe neurodevelopmental impairment, cerebral palsy, and lower Bayley-III motor scores. Baseline urinary I-FABP levels were similar between groups. When compared to controls, infants with NEC had urinary I-FABP concentrations that were higher at diagnosis (median 11 vs 2.6 ng/ml, p = 0.006) and lower post-NEC (median 1 vs 5 ng/ml, p = 0.002). Diagnosis I-FABP levels were not associated with gastrointestinal or neurodevelopmental outcomes at 22-26 months corrected age. In extremely preterm infants, urinary I-FABP was elevated at NEC diagnosis and lower post-NEC compared to matched controls. I-FABP levels were not associated with adverse gastrointestinal or neurodevelopmental outcomes. Urinary intestinal fatty acid binding protein (I-FABP) levels are increased at diagnosis of NEC and fall to below baseline after NEC in extremely preterm infants. Urine I-FABP levels at NEC diagnosis are not associated with cholestasis, intestinal stricture or obstruction, need for additional intestinal surgery after NEC, or neurodevelopmental outcomes at 22-26 months corrected age. Urine I-FABP levels may be useful in the diagnosis of NEC. Diagnostic I-FABP levels do not predict short-term gastrointestinal or neurodevelopmental outcomes after NEC.

Lactobacillus paragasseri SBT2055 attenuates obesity via the adipose tissue-muscle-gut axis in obese mice

The anti-obesity effects of Lactobacillus paragasseri (L. paragasseri) have been reported, but the exact mechanisms have not been elucidated. There are also no reports on the impact of L. paragasseri on the gut microbiota environment. Recently, the incidence of sarcopenia due to obesity has increased regardless of age, exacerbating metabolic disorders caused by obesity. Therefore, we investigate the beneficial effects of L. paragasseri SBT2055 (LG2055) on obesity along with obese sarcopenia and gut microbiome changes. C57BL/6 J mice were fed a high-fat diet (HFD) and LG2055 (1×108 or 1×1010 CFU/mice, low-dose LG2055 (LP) or high-dose LG2055 (HP), respectively was administered orally. LG2055 supplementation significantly reduced white adipose tissues compared to the HFD group and modified plasma lipid profiles to normal levels. The anti-obesity efficacy of LG2055 was due to increased lipid excretion into feces by reducing the mRNA levels of fatty acid binding protein 1 (Fabp1), fatty acid binding protein 2 (Fabp2), fatty acid transport protein 4 (Fatp4), cluster of differentiation 36 (Cd36), and apolipoprotein 48 (ApoB48) in the small intestine. The body fat reduction inhibits ectopic lipid accumulation in the muscles, leading to improvements in muscle mass, grip strength, hind leg thickness, muscle protein levels, and muscle fiber size in both LP and HP groups. LG2055 increased gut microbiota diversity and elevated the levels of Bacteroidota, resulting in a lower Firmicutes/Bacteroidota ratio compared to the HFD group. Changes in the Bacteroidota showed a negative correlation with body fat and plasma free fatty acid (FFA) while exhibiting a positive correlation with lean body mass, grip strength, and hind leg thickness. Our results demonstrated the anti-obesity effects of LG2055 through the white adipose tissue (WAT)-muscle-gut axis, suggesting its potential as an anti-obesity agent.

Limosilactobacillus Fermentun ZS09 Can Improve Antibiotic-Induced Motor Dysfunction in Mice by Regulating the Brain-Gut Functions.

When consumed in appropriate quantities, probiotics, which are live microorganisms, are good for health. In this study, a mouse model of antibiotic-induced dyskinesia was established using a sterile mixed antibiotic solution to investigate the preventive impact of Limosilactobacillus fermentum ZS09 (LFZS09) on this condition in mice. Following modeling, alterations in the serum and brain tissue of mice were assessed for motor measures such as running and swimming, malondialdehyde (MDA), superoxide dismutase, reduced glutathione, interleukin (IL-6, IL-10), and tumor necrosis factor (TNF)-α. The mouse cecum was used to evaluate the relative mRNA expression levels of the intestinal barrier genes, namely occludin-1, zona occludens-1 (ZO-1), and claudin-1. The relative mRNA expression levels of cAMP-response element binding protein (CREB), extracellular signal-regulated kinase (ERK), and brain-derived neurotrophic factor (BDNF) genes in the mouse brain tissue were also evaluated. Compared with the model group, LFZS09 considerably increased the swimming and running duration of mice, significantly decreased the levels of the inflammatory factors TNF-α and IL-6 and increased SOD expression in the mouse brain, and decreased MDA accumulation in the mouse brain and serum. Furthermore, LFZS09 upregulated occludin-1 gene expression in the cecal tissue to maintain the intestinal barrier, which in turn maintained the normal physiological function of the body. LFZS09 also enhanced the effect of BDNF and increased the expression of BDNF metabolic pathway-related genes, namely CREB, ERK1/2, and BDNF, in the mouse brain tissue. LFZS09 increased the number of Lactobacillus and Bifidobacterium in the gut of mice with motor dysregulation, and decreased the number of Enterococcus and Clostridium perfringens. The findings indicate that LFZS09 regulates antibiotic-induced motor impairment in mice, thereby offering a theoretical foundation for future studies and probiotic or parabiotics production aimed at augmenting motor function.

Severe Hyporesponsiveness to Erythropoiesis-Stimulating Agents in Patients on Chronic Hemodialysis-Reconsidering the Relationship with Thrombo-Inflammation and Oxidative Stress.

Besides a multitude of consequences patients on chronic renal replacement therapy have, anemia is one of the most prominent factors making a significant number of patients dependent on erythropoiesis-stimulating agent (ESA) therapy. The aim of this study was to examine the relationship between the levels of a broad spectrum of thrombo-inflammatory and oxidative stress-related biomarkers and the presence and level of ESA hyporesponsiveness in patients undergoing regular chronic hemodialysis. This cross-sectional study included 96 patients treated with chronic hemodialysis. Levels of several thrombo-inflammatory and oxidative stress-related biomarkers, as well as demographic, clinical, and laboratory analyses, were collected and analyzed based on the calculated value of the ESA-hyporesponsiveness index (EHRI). In the analyzed sample, 58 patients received ESAs. Of all the investigated parameters, only body mass index (BMI), level of plasminogen activator inhibitor-1, and level of L-type fatty acid binding protein (L-FABP) were observed as significant predictors of EHRI. A significant diagnostic potential for ESA resistance has been observed in BMI and L-FABP between ESA-resistant and ESA-non-resistant groups of patients (p = 0.004, area under the curve 0.763 and p = 0.014, area under the curve 0.712, respectively) with the cut-off values of 25.46 kg/m2 and 5355.24 ng/mL, respectively. Having a BMI of 25.46 kg/m2 or less and an L-FABP level higher than 5355.24 ng/mL were observed as significant predictors of ESA resistance (odds ratio 9.857 and 6.125, respectively). EHRI was positively predicted by low BMI and high levels of plasminogen activator inhibitor-1 and L-FABP. High levels of L-FABP and low BMI have been observed as strong predictors of ESA resistance.

Elevated Circulatory Levels of UL16 Binding Protein 1 Positive Microparticles Are Associated With Acute Myocardial Infarction and its Severity.

Atherosclerosis is a vascular inflammatory disease characterized by the activation and stress of various inflammatory cells, leading to the development of coronary artery disease and subsequently acute myocardial infarction (AMI). Among AMI cases, ST-segment elevation myocardial infarction (STEMI) is typically more severe than non-STEMI (NSTEMI). UL16-binding proteins (ULBPs), which are NKG2D ligands, can be expressed on the surface of stressed and activated cells, prompting these cells to generate microparticles (MPs). Consequently, MPs carrying ULBPs, particularly ULBP1 (ULBP1+ MPs), may be released into the bloodstream. This study aimed to investigate the association between ULBP1+ MPs and the presence of AMI and its severity. We recruited 58 AMI patients and 45 age-matched control subjects. Levels of ULBP1+ MPs and ULBP1+ MPs originating from T lymphocytes (ULBP1+ TMPs) were measured using flow cytometry. Both ULBP1+ MP and ULBP1+ TMP levels were significantly elevated in AMI patients compared to controls. Elevated levels of these MPs were independent risk factors for AMI with odds ratios (OR) of 4.3 (95%CI=1.5-12.3) for ULBP1+ MPs and 5.8 (95%CI=2.0-17.0) for ULBP1+ TMPs. Additionally, ULBP1+ TMP levels were significantly higher in STEMI patients compared to NSTEMI patients, with an independent association observed between ULBP1+ TMPs and STEMI (OR=3.9; 95%CI=1.2-12.8). Elevated levels of ULBP1+ MPs and ULBP1+ TMPs are associated with AMI and its severity. These biomarkers could serve as indicators of vulnerable plaques that lead to AMI.

6652 Precision Diagnostic Approaches for Assessing Clinical Vitamin D Status

Abstract Disclosure: Z. Shahidzadeh Yazdi: None. E.A. Streeten: None. H.B. Whitlatch: Grant Recipient; Self; Regeneron Pharmaceuticals. M.E. Montasser: Grant Recipient; Self; Regeneron Pharmaceuticals. A.L. Beitelshees: None. S.I. Taylor: Consulting Fee; Self; Ionis Pharmaceuticals Inc.. Background . The body has evolved effective homeostatic mechanisms to maintain free 1,25-dihydroxyvitamin D [1,25(OH)2D] within narrow physiological ranges. Using a mathematical model to quantitate 24-hydroxylase activity, we concluded that mild-moderate vitamin D [VitD] deficiency suppresses 24-hydroxylase activity (the first line of defense), thereby suppressing clearance of 1,25(OH)2D. Severe VitD deficiency triggers secondary hyperparathyroidism (the second line of defense) to sustain physiological levels of 1,25(OH)2D. Objective. To compare performance of various indices of VitD status in predicting whether homeostatic mechanisms have been triggered. Methods. We studied 11 otherwise healthy VitD deficient (25-hydroxyvitamin D [25(OH)D] ≤20 ng/mL) participants before and after VitD3 supplementation (50,000 IU once or twice a week depending on BMI for 4-6 weeks). We measured 25(OH)D, 1,25(OH)2D, 24,25-dihydroxyvitamin D [24,25(OH)2D], PTH, and FGF23 before and after VitD3 supplementation. We calculated three VitD metabolite ratios and also a PTH index (i.e., PTH level before divided by PTH level after VitD3 supplementation) to normalize PTH levels relative to each individual’s setpoint. We then compared the correlation between the PTH index and various indices of VitD status. Results. VitD3 supplements induced a 2.7-fold increase (p=0.0006) in mean 25(OH)D and a 4.3-fold increase (p=0.0002) in 24,25(OH)2D, but did not change 1,25(OH)2D, PTH, or FGF23. While relative 24-hydroxylase activity (h) was highly correlated with the 1,25(OH)2D/24,25(OH)2D ratio (ρ2=0.94; p=3E-13), it was less well correlated with the 24,25(OH)2D/25(OH) ratio (ρ2=0.67; p=3E-06) and baseline total 25(OH)D (ρ2=0.72; p=7E-07). Furthermore, we investigated the correlation between the PTH index and baseline 25(OH)D and three VitD metabolite ratios. The correlation coefficient was higher when we plotted the PTH index as a function of baseline 25(OH)D before VitD3 supplementation (R2=0.23; p=2E-06) compared to the correlation of baseline PTH with baseline 25(OH)D (R2=0.08; p=5E-05). While the correlation coefficient for the correlation of PTH index with 1,25(OH)2D/24,25(OH)2D was 0.60 (R2=0.36; p=0.0002), it was 0.44 for 25(OH)D/1,25(OH)2D ratio (R2=0.20; p=0.0001) and 0.35 for the 24,25(OH)2D/25(OH)D ratio (R2=0.12; p=2E-06). Conclusions. Measuring total 25(OH)D level did not provide optimal assessment of clinical VitD status – probably because it does not account for the threefold inter-individual variation in VitD binding protein level. Of all the indices, the 1,25(OH)2D/24,25(OH)2D ratio best predicted triggering of two homeostatic mechanisms: suppression of 24-hydroxylase and induction of secondary hyperparathyroidism due to VitD deficiency. Presentation: 6/2/2024

Early pregnancy exposure to Microcystin-LR compromises endometrial decidualization in mice via the PI3K/AKT/FOXO1 signaling pathway

Previous experimental studies have found that exposure to Microcystin-leucine arginine can impact pregnancy outcomes in female mice. The impact of MC-LR on early pregnancy in mammals is not yet well understood. Both mice and humans need to undergo decidualization to maintain pregnancy. In this study, we tried to evaluate whether MC-LR affects decidualization process in mice. Our research showed that MC-LR decreased maternal weight gain, uterine weight, and implantation site weight. These findings suggested that MC-LR exerted adverse effects on decidualization. In mice, we examined decreased number of polyploid decidual cells, but marked proliferation of mouse endometrial stromal cells the expression levels of prolactin (PRL)and insulin-like growth factor binding protein 1 (IGFBP1) were significantly downregulated in the decidual tissue and primary endometrial stromal cells following MC-LR treatment. Furthermore, further in vitro experiments identified that MC-LR promoted endometrial stromal cell division and cycle transition. Lastly, our study demonstrated that MC-LR impaired decidualization through the PI3K/AKT/FOXO1 pathway. Collectively, these data suggested that exposure to MC-LR impaired decidualization during early pregnancy.

Insights for possible association and impact of thyroidectomy to osteoarthritis

Background and aim of studyThyroidectomy and osteoarthritis have drawn more attention in last decades due to increase various local and systemic risk factors. This study is aimed to determine the association and impact between thyroidectomy and osteoarthritis by serological measurement of most specific related markers.ResultsMeasurement of thyroid markers showed the level of thyroid-stimulating hormone (TSH) was significantly increased, while parathyroid hormone (PTH), triiodothyronine (T3), and thyroxine (T4) levels were decreased in osteoarthritis subjected to thyroidectomy group (OTG) when compared to hyperthyroidism subjected to thyroidectomy group (TG), osteoarthritis group (OG), and healthy control group (CG). Detection the activity of bone markers showed the level of R-factor was significantly elevated concomitant with significant reduction in Dickkopf related protein 1 (DKK1), human hyaluronan-binding protein 2 (HABP2), osteocalcin (OC) in OG and OTG groups, while osteopontin (OPN) and procollagen I C-terminal propeptide (PICP) were significantly increased and decreased in TG and OTG. Furthermore, the level of S100 Calcium binding protein (S100CBP) showed significant decreased in patient’s groups, while TG with OTG groups exhibited significant reduction in sclerostin (SOST) concentration. Regarding the inflammatory markers, the levels of interleukin-1 (IL-1) was increased in the OTG, while the level of interleukin-10 (IL-10) was increased in OG and TG groups, and reduced in OTG. While, the level of transforming growth factor-beta (TGF-β) was decreased in OG and TG associated with significant increases in tumor necrosis factor-alpha level (TNF-α) in OTG. Measurement of oxidant and antioxidant activity markers showed the levels of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) were significantly reduced in all patient’s groups compared to control, except the level of CAT in TG, whereas, malondialdehyde (MDA) level was increased in OG and OTG patients. Furthermore, the levels of Alkaline phosphatase (ALP), C-Reactive protein (CRP), and erythrocyte sedimentation rate (ESR) were increased in all patient groups compared to control, while fatty acid-binding protein (FABP) level was increased in OTG only.ConclusionThis unique study in Iraq is identified the interaction effect and impact of thyroidectomy to osteoarthritis according to the results that showed various changes and degree of correlation of study biomarkers in all patient groups, however more depth of specific quantitative and qualitative studies are required to support this association and the impact claim at molecular level.

Changes of Ca2+ release through ryanodine receptor 1 in pork under different postmortem chilling rates

The role of postmortem chilling rate in regulating Ca2+ release through ryanodine receptor 1 (RyR1) in pork microstructure and tenderness were evaluated. The pork was allocated to the low chilling rate (LCR, 4.26°C/h), medium chilling rate (MCR, 8.89°C/h), and high chilling rate (HCR, 13.33°C/h) group. Sarcomere super-contraction and fiber damage were obtained in HCR samples, leading to the lowest shear force (P < 0.05). Under HCR, Ca2+ concentration significantly increased in sarcoplasm and decreased in sarcoplasmic reticulum were found at 2-5 h postmortem compared to other groups (P < 0.05). RyR1 and dihydropyridine receptor (DHPR) levels were higher and 12 kDa FK506 binding protein (FKBP12) level was lower in HCR samples at 6 h postmortem (P < 0.05). Therefore, HCR (13.33°C/h) may enhance Ca2+ release by up-regulating RyR1 level with DHPR activation increasing and FKBP12 inhibition decreasing, causing myofibril damage from sarcomere super-contraction to improve pork tenderness at early postmortem.

Evaluation of serum IL 18 / IL 18 binding protein ratio and their relation with IL- 18 gene polymorphisms in sample of Iraqi type 2 diabetes mellitus patients. A case control study.

To evaluate the ratio of interleukin18 and interleukin18 binding protein in type 2 diabetes mellitus patients, and its relation with the presence of interleukin18-607C/A and interleukin18-137G/C gene polymorphisms and the type of complications. The case-control study was conducted at the endocrinology clinic of the Madinat Al-Imamin Al-Kazemin Teaching Hospital, Iraq, from September 2020 to July 2021, and comprised diagnosed patients of type 2 diabetes mellitus, and healthy controls matched for age and gender. Blood samples were obtained that were processed for serum separation. Serum interleukin18 and interleukin18 binding protein levels were assessed, and part of the sample was used for deoxyribonucleic acid extraction using tetra-primer amplification refractory mutation system polymerase chain reaction with four specific primers for interleukin18-607C/A and interleukin-18-137G/C gene polymorphisms in both the groups. Data was analysed using SPSS 20. Of the 168 subjects, 86(51.2%) were patients; 67(77.9%) females and 19(22.1%) males with mean age 52±8.97 years. There were 82(48.8%) controls; 56(68.3%) females and 26(31.7%) males with mean age 48±9.44 years (p>0.05). Higher serum level of interleukin18 and lower level of interleukin18 binding protein were seen in type 2 diabetes mellitus group compared to the controls (p<0.001). Interleukin18-137G/C and interleukin18-607C/A mutant alleles had odd ratios 3.52 (confidence interval: 1.91- 6.63) and 3.25 (confidence interval: 1.77-5.83), respectively, as risk factors for the occurrence of type 2 diabetes mellitus. There was an association of interleukin18- 137G/C homozygous mutant genotype with the occurrence of retinopathy among type 2 diabetes mellitus patients (p=0.046), but risk allele C was not associated with retinopathy (p>0.05). The presence of interleukin18-137G/C and interleukin18-607C/A gene polymorphism might be considered a risk factor for type 2 diabetes mellitus.

Evaluation of serum Cold Inducing RNA Binding Protein level in Acne Vulgaris patients

Evaluation of serum Cold Inducing RNA Binding Protein level in Acne Vulgaris patients