Metabolic Status Research Articles

Association of Obesity Based on Different Metabolic Status with Risk of Gout Occurrence in Patients: A National Study.

Obesity often co-exists with metabolic abnormalities, but the results of studies on the relationship between obesity, metabolic abnormalities and the risk of gout are inconsistent. We aimed to study whether there was a mutual regulation between obesity, metabolic abnormalities and the risk of gout. We conducted a cross-sectional study to expound the association between obesity based on different metabolic statuses and the risk of gout. Patients were derived from Nationwide Readmission Database (2018 sample). A total of 9,668,330 records were recruited for analysis from January to December. The risk of gout in the obesity group, metabolic abnormalities group and obesity combined with metabolic abnormalities group was 1.67 times (OR=1.67, 95%CI 1.64-1.70), 3.12 times (OR=3.12, 95%CI 3.09-3.15) and 4.27 times (OR=4.27, 95%CI 4.22-4.32) higher than that in the normal control group. For different metabolic components, OR value was highest in hypertension group (OR=2.65, 95%CI 2.60-2.70 and OR=4.85, 95%CI 4.73-4.97), followed by dyslipidemia group (OR=2.23, 95%CI 2.16-2.30 and OR=3.74, 95%CI 3.55-3.95) and in hyperglycemia group (OR=1.73, 95%CI 1.66-1.80 and OR=2.94, 95%CI 2.78-3.11). Fewer components of metabolic syndrome were associated with a lower risk of gout in both nonobese and obese patients. When metabolic abnormalities were present, obesity induced a higher risk of gout. Different components of metabolic abnormalities had different effects on the risk of gout occurrence, and the number of metabolic abnormalities was closely related to the risk of gout occurrence. Follow-up and intervention methods targeting obesity and metabolic abnormalities should be considered for patients with gout.

The Ketogenic Diet as a Treatment for Mood Disorders

Abstract Purpose of Review The ketogenic diet is a low carbohydrate, moderate protein, and high fat diet which results in a metabolic state known as ketosis, in which fats are broken down into ketone bodies. The ketogenic diet is a 100-year-old evidence-based treatment for epilepsy and is gaining popularity as a treatment for various mental disorders, including mood disorders. Our objective is to explain the potential mechanisms through which ketogenic diets may improve the pathophysiology of mood disorders and provide a comprehensive review of recent clinical literature on the topic Recent Findings Mood disorders are associated with several proposed pathophysiological mechanisms, including mitochondrial dysfunction, oxidative stress, inflammation, and insulin resistance. The ketogenic diet shows promise in addressing these underlying pathophysiological mechanisms and emerging clinical data suggest that ketogenic diets may improve symptoms in people with mood disorders. Summary The ketogenic diet shows promise in the treatment of mood disorders. This metabolic intervention has the potential to directly target underlying disease mechanisms, potentially reduce the need for medications, and reduce common side effects and comorbidities, such as weight gain and insulin resistance.

Effect of Jianpi Shengxue Tablet on Iron Metabolism and Nutritional Status in Patients with Renal Anemia: A Prospective, Randomized, Open, Parallel Controlled and Multicenter Clinical Study.

This study aimed to analyze the clinical efficacy of the Jianpi Shengxue tablet for treating renal anemia. A total of 200 patients with renal anemia from December 2020 to December 2022 were enrolled and randomly divided into two groups. Patients in the control group were treated with polysaccharide-iron complex, and those in the experimental group were administered Jianpi Shengxue tablet. After 8 weeks of continuous treatment, the therapeutic outcomes regarding anemia were compared between the two groups. After treatment, the red blood cell (RBC) count, hematocrit (HCT), reticulocyte percentage (RET), ferritin (SF), serum iron (SI), transferrin saturation (TSAT), and serum albumin (ALB) all increased (P<0.01), and the clinical symptom score and total iron binding capacity decreased (P<0.01) in the experimental group. Moreover, the improvements in RBC, HCT, RET, SF, SI, TAST, ALB, and clinical symptoms (fatigue, anorexia, dull skin complexion, numbness of hands and feet) in the experimental group were significantly greater than those in the control group (P<0.05). The total effective rate for treating renal anemia was significantly higher in the experimental group than in the control group (P<0.01). The Jianpi Shengxue tablet demonstrates efficacy in treating renal anemia, leading to significant improvements in the laboratory examination results and clinical symptoms of patients with renal anemia.

Serum ferritin levels in children of simple febrile seizures in tertiary institute

Background: Seizure onset is impacted by a number of variables, including genetics, diet, geography, concurrent illnesses, metabolic state, history of head trauma, and blood levels of particular minerals. Due to the fact that iron is required for the proper functioning of a number of enzymes and neurotransmitters in the central nervous system, low blood ferritin levels may lower the seizure threshold. The aim of the study was to determine the association between serum ferritin levels and simple febrile seizures. Methods: The present observational study was conducted in department of pediatrics of a tertiary institute and included a total of 200 study subjects who visited to pediatric OPD/emergency room with febrile illness. The data was collected with the help of a structured clinical proforma. The collected data was recorded in Microsoft Excel sheet and statistical analysis was done with the help of SPSS version 21.0. Results: In our study, the maximum number of the study subjects were between 13 and 24 months (35%) with male to female ratio 1.2:1. In patients with simple febrile seizure the mean Hb level was 9.1±1.4 gm/dl, the mean MCV was 72.6±7.4 f1, mean MCH was 23.73±3.2 pg and mean serum ferritin was 13.4±9.5 ng/ml as compared to those patients with febrile illness without seizure the mean Hb level was 11.5±1.2 gm/dl, mean MCV was 82.1±5.5 f1, mean MCH was 29.6±2.9 pg and mean serum ferritin was 33.6±20.2 ng/ml. Conclusions: It is concluded that the low serum ferritin level is a risk factor of simple febrile seizure.

Metabolic Modulation-Mediated Antibiotic and Immune Activation for Treatment of Chronic Lung Infections.

The Pseudomonas aeruginosa biofilm in recalcitrant chronic lung infections not only develops high antimicrobial tolerance but also induces an aberrant host inflammatory response. The metabolic condition plays a vital role in both the antimicrobial susceptibility of bacteria and the inflammatory response of immune cells, thereby offering a potential therapeutic target. Herein, we described a metabolic modulation strategy by using ultrasound-responsive liposomal nanoparticles containing a sonosensitizer and a hypoxia-activated prodrug against biofilm-associated chronic lung infections. Under ultrasound stimulation, the sonosensitizer generates antibacterial reactive oxygen species by oxygen consumption. Subsequently, the oxygen consumption-mediated hypoxia not only induces the anaerobic metabolism of bacteria for antibiotic activation but also triggers the glycolysis pathway of immune cells for inflammatory activation. Such metabolic modulation strategy demonstrated efficient therapeutic efficacy for P. aeruginosa biofilm-induced chronic lung infections in mice models and provides a promising way for combating biofilm-associated chronic infections.

Dietary Supplementation with Naringin Improves Systemic Metabolic Status and Alleviates Oxidative Stress in Transition Cows via Modulating Adipose Tissue Function: A Lipid Perspective

Dairy cows face metabolic challenges around the time of calving, leading to a negative energy balance and various postpartum health issues. Adipose tissue is crucial for cows during this period, as it regulates energy metabolism and supports immune function. Naringin, one of the main flavonoids in citrus fruit and their byproducts, is a potent antioxidant and anti-inflammatory phytoconstituent. The study aimed to evaluate the effects of supplemental naringin on performance, systemic inflammation, oxidative status, and adipose tissue metabolic status. A total of 36 multiparous Holstein cows (from ~21 d prepartum through 35 d postpartum) were provided a basal control (CON) diet or a CON diet containing naringin (NAR) at 30 g/d per cow. Supplemental NAR increased the yield of raw milk and milk protein, without affecting dry matter intake. Cows fed NAR showed significantly lower levels (p &lt; 0.05) of serum non-esterified fatty acid (NEFA), C-reactive protein, IL-1β, IL-6, malonaldehyde, lipopolysaccharide (LPS), aspartate aminotransferase, and alanine aminotransferase, but increased (p &lt; 0.05) glutathione peroxidase activity relative to those fed CON. Supplemental NAR increased (p &lt; 0.05) adipose tissue adiponectin abundance, decreased inflammatory responses, and reduced oxidative stress. Lipidomic analysis showed that cows fed NAR had lower concentrations of ceramide species (p &lt; 0.05) in the serum and adipose tissue than did the CON-fed cows. Adipose tissue proteomics showed that proteins related to lipolysis, ceramide biosynthesis, inflammation, and heat stress were downregulated (p &lt; 0.05), while those related to glycerophospholipid biosynthesis and the extracellular matrix were upregulated (p &lt; 0.05). Feeding NAR to cows may reduce the accumulation of ceramide by lowering serum levels of NEFA and LPS and increasing adiponectin expression, thereby decreasing inflammation and oxidative stress in adipose tissue, ultimately improving their systemic metabolic status. Including NAR in periparturient cows’ diets improves lactational performance, reduces excessive lipolysis in adipose tissue, and decreases systemic and adipose tissue inflammation and oxidative stress. Integrating lipidomic and proteomic data revealed that reduced ceramide and increased glycerophospholipids may alleviate metabolic dysregulations in adipose tissue, which in turn benefits systemic metabolic status.

Supplementation of the Combination of Quercetin and Vitamin E Alleviates the Effects of Heat Stress on the Uterine Function and Hormone Synthesis in Laying Hens

Chickens are sensitive to heat stress because their capacity to dissipate body heat is low. Hence, in chickens, excessive ambient temperature negatively influences their reproductive performance and health. Heat stress induces inflammation and oxidative stress, thereby rendering many reproductive organs dysfunctional. In this study, we evaluated the effects of the supplementation of dietary quercetin and vitamin E on the uterine function, eggshell quality via estrogen concentration, calcium metabolism, and antioxidant status of the uterus of laying hens under heat stress. The ambient temperature transformation was set at 34 ± 2 °C for 8 h/d (9:00 am–5:00 pm), which was followed by 22 °C to 28 °C for 16 h/d. Throughout the experiment, the relative humidity in the chicken’s pen was at 50 to 65%. A total of 400 Tianfu breeder hens (120-days-old) were randomly divided into four dietary experimental groups, including basal diet (Control); basal diet + 0.4 g/kg quercetin; basal diet + 0.2 g/kg vitamin E; and basal diet + the combination of quercetin (0.4 g/kg) and vitamin E (0.2 g/kg). The results show that the combination of quercetin and vitamin E significantly increased the serum alkaline phosphatase levels and the antioxidant status of the uterus (p &lt; 0.05). In addition, the combination of quercetin and vitamin E significantly increased the concentrations of serum estrogen and progesterone, as well as elevated the expression of hypothalamic gonadotropin-releasing hormone-1 and follicular cytochrome P450 family 19 subfamily A member-1 (p &lt; 0.05). We also found that the calcium levels of the serum and uterus were significantly increased by the synergistic effects of quercetin and vitamin E (p &lt; 0.05), and they also increased the expression of Ca2+-ATPase and the mRNA expression of calcium-binding-related genes in the uterus (p &lt; 0.05). These results are consistent with the increased eggshell quality of the laying hens under heat stress. Further, the combination of quercetin and vitamin E significantly increased the uterine morphological characteristics, such as the height of the uterine mucosal fold and the length of the uterine mucosa villus of the heat-stressed laying hens. These results collectively improve the uterine function, serum and uterine calcium concentration, eggshell strength, and eggshell thickness (p &lt; 0.05) in heat-stressed laying hens. Taken together, we demonstrated in the present study that supplementing the combination of dietary quercetin and vitamin E alleviated the effects of heat stress and improved calcium metabolism, hormone synthesis, and uterine function in the heat-stressed laying hens. Thus, the supplementation of the combination of quercetin and vitamin E alleviates oxidative stress in the eggshell gland of heat-stressed laying hens, thereby promoting calcium concentration in the serum and eggshell gland, etc., in laying hens. Hence, the combination of quercetin and vitamin E promotes the reproductive performance of the laying hens under heat stress and can also be used as a potent anti-stressor in laying hens.

Targeting Acute Myeloid Leukemia Stem Cells Through Perturbation of Mitochondrial Calcium.

Acute myeloid leukemia stem cells (LSCs) are uniquely reliant on oxidative phosphorylation (OXPHOS) for survival. Moreover, maintenance of OXPHOS is dependent on BCL-2, creating a therapeutic opportunity to target LSCs using the BCL-2 inhibitor venetoclax. While venetoclax-based regimens have shown promising clinical activity, the emergence of drug resistance is prevalent. Thus, in the present study, we investigated how mitochondrial properties may influence venetoclax responsiveness. Our data show that utilization of mitochondrial calcium is fundamentally different between drug-responsive and non-responsive LSCs. By comparison, venetoclax-resistant LSCs demonstrate a more active metabolic (i.e. OXPHOS) status with relatively high levels of calcium. Consequently, we tested genetic and pharmacological approaches to target the mitochondrial calcium uniporter, MCU. We demonstrate that inhibition of calcium uptake reduces OXPHOS and leads to eradication of venetoclax-resistant LSCs. These findings demonstrate a central role for calcium signaling in LSCs and provide an avenue for clinical management of venetoclax resistance.

#1564 Clinical implication of hyperfiltration and metabolic syndrome on the cardiovascular events, kidney failure, and all-cause mortality

Abstract Background and Aims Renal hyperfiltration (RHF) and metabolic syndrome (MetS) increase the risk of cardiovascular disease, end stage kidney disease (ESKD), and all-cause mortality. While RHF is strongly related to the metabolic risk, it is little known how the combined association of these two factors affects the risk of MetS-related complication, cardiovascular disease, and all-cause mortality. Method We reviewed the National Health Insurance Service database of Korea for people who received national health screenings between 2009 and 2011. RHF was defined as estimated glomerular filtration rate (eGFR) &amp;gt; 95th percentile after stratification for age, sex, height and weight, and normal renal filtration defined as eGFR 25-75th percentile. MetS was considered as the presence of three or more of the metabolic risks. Individuals were compared based on the presence of RHF and MetS. Age, sex, and Charlson comorbidity index matching were performed to reduce the selection bias in the study population. Finally, a total of 276,952 patients were matched, with 69,238 patients in each group, in a 1:1:1:1 ratio based on both their metabolic status and the presence of RHF. Results In multivariate Cox analysis, in comparison to normal renal filtration without MetS, RHF without MetS does not increase the risk of progression to ESKD. RHF patients increased the risk of progression to ESKD (aHR 2.75, 95% CI 1.38-5.50) only when combined with MetS. Moreover, irrespective of metabolic status, the risk of cardiovascular events (without MetS: aHR 1.08, 95% CI 1.00-1.17), (with MetS: aHR, 1.49; 95% CI, 1.38-1.60) and all-cause mortality (without MetS: aHR 1.29, 95% CI 1.20-1.40), (with MetS: aHR, 1.49; 95% CI, 1.37-1.62) increases significant in RHF patients. Notably, RHF synergistically increases the risk of cardiovascular events when accompanied with MetS (p for interaction = 0.041). However, RHF increases the risk of all-cause mortality more significantly without MetS than with MetS (p for interaction = 0.005). Conclusion The clinical implication of RHF is dependent on MetS status, and a significant interaction between the two factors is observed. To establish a treatment strategy for patients with RHF, MetS status must be considered.

#1492 Metabolic switch in CD8+ T cells may influence immune response in chronic antibody-mediated rejection (CAMR)

Abstract Background and Aims CAMR is the main cause of chronic graft injury and subsequent graft loss, but its pathogenesis is still largely unclear. Our group demonstrated an increase in CD8+ T cells infiltrating biopsies from CAMR patients (PMID: 20595199), but their role remains to be defined. Recently, immunometabolism has emerged as a field connecting cell energy metabolism with the immune cell differentiation and functions. Particularly, the permanent aerobic glycolysis of CD8+ lymphocytes induces their transition from naïve to activated state and effector T cells (PMID: 37315709). Thus, the aim of the study was to investigate the molecular mechanisms underlying the development of CAMR by the analysis of gene expression profiles of CD8+ T lymphocytes in conjunction with their metabolic state. Method We enrolled 14 patients with biopsy-proven CAMR and 12 stable transplant recipients with normal graft histology and function (control group). CD8+ T cells were purified by CD8 MicroBeads (Miltenyi Biotec) then counted (TC20™ Automated Cell Counter). Gene expression profiles of CD8+ T lymphocytes isolated from both groups were assessed using Agilent microarrays. Data obtained were statistically and functionally evaluated (IPA software) and validated by qPCR. Oxygen consumption rate (OCR) in CD8+ and CD8- cells was measured by a Resipher oxygen sensing lid (Lucid Scientific Inc., USA). The contribution of mitochondrial respiration to OCR was investigated in isolated CD8+ T cells from CAMR and controls treated with rotenone/antimycin A (Rot/AA), oligomycin (Olygo) or carbonyl cyanide-p-trifluoromethoxyphenylhydrazone (FCCP) to evaluate spare respiratory capacity (SRC), ATP-linked respiration, proton leak and maximal respiration. Results Gene expression profiles of CD8+ T cells showed a characteristic alteration of lipid metabolism in CAMR patients with the triglyceride biosynthesis pathway (p = 2.69E-3) as the most altered pathway and several genes de-regulated all potentially involved in the altered metabolic state of CD8+ T cells. Among others, we validated the increased expression of Nicotinamide Phosphoribosyltransferase (NAMPT) (FC = +2.39), the rate-limiting enzyme of nicotinamide adenine dinucleotide (NAD+) salvage pathway involved in the glycolysis progression, mostly activated in effector T cells. We then decided to evaluate the OCR and the metabolic state of CD8+T cells. Basal OCR was higher in CD8+ rather than CD8- cells, but with different trends among cells isolated from control and CAMR patients. Indeed, CD8+ cells from CAMR patients showed higher OCR compared to control, while OCR was lower in CD8- from CAMR rather than control patients. CD8+ OCR from both CAMR and control patients was mostly dependent on mitochondrial respiration, since it was deeply reduced by Rot/AA treatment. Interestingly, inhibitory response to Oligo treatment by CD8+ cells from CAMR patients was modest, while OCR was noticeably stimulated by FCCP in these cells, suggesting that mitochondrial oxygen uptake was not ATP linked but rather associated with increased uncoupling. These data suggest that CD8+ T cells from CAMR patients are activated effector T cells primarily utilizing aerobic glycolysis. To confirm this hypothesis, we evaluated the gene expression levels of: i) HIF1a, which involves permanent dependence on glycolysis even in the presence of oxygen (Warburg effect); ii) fatty acid transporter CD36, whose levels mimic an energy dependence on the beta oxidation of fatty acids, a process activated in memory T cells. We confirmed an increased expression of HIF1a and a reduced expression of CD36 in CD8+T cells from CAMR patients compared to controls (p&amp;lt;0.05), that confirm the T effector phenotype. Conclusion Our data suggest that CD8+ T cell from CAMR patients showed permanent dependency on glycolysis leading to altered immune phenotype and response, thus indicating novel opportunities to modulate the immune system for therapeutic purposes in kidney transplanted patients and reduce graft rejection.

Mediterranean Diet Combined with Regular Aerobic Exercise and Hemp Protein Supplementation Modulates Plasma Circulating Amino Acids and Improves the Health Status of Overweight Individuals

Plant protein is considered a sustainable health-promoting strategy to prevent metabolic syndrome. Lifestyle changes (including dietary patterns and exercise) have been demonstrated to exert an effect on human health by modulating the biochemical status in humans. The objective of this study was to assess whether supplementation with hemp protein within a Mediterranean diet context together with exercise could help to ameliorate the metabolic statuses of patients prone to developing metabolic syndrome. For this study, 23 patients followed with Mediterranean diet and engaged in aerobic exercise according to the WHO’s recommendations, while also being supplemented with hemp protein, for 12 weeks. A comparison of anthropometric, biochemical, and mineral data as well as amino acid values was made between the start and the end of the study, with the subjects acting as their own control group. Statistical analyses included a paired t-test, Wilcoxon paired test, Pearson correlation coefficient, and Sparse Partial Least Squares Discriminant Analysis to evaluate significant differences and correlations among parameters. There were statistically significant changes in total cholesterol, HDL-C (+52.3%), LDL-C (−54.0%), and TAG levels (−49.8%), but not in glucose plasma levels. Following the intervention, plasma concentrations of some amino acids, including α-aminoadipic acid, phosphoethanolamine, and 1-metylhistidine, increased, whereas those of asparagine and alanine declined. Different correlations between amino acids and the other parameters evaluated were reported and discussed. A Mediterranean diet combined with regular aerobic exercise, together with protein supplementation, can highly improve the metabolic parameters and anthropometric parameters of subjects with obesity and impaired glucose levels, ameliorating their health status and likely delaying the development of metabolic syndrome.

Nitrogen availability is important for preventing catastrophic mitosis in fission yeast.

Mitosis is a critical stage in the cell cycle, controlled by a vast network of regulators responding to multiple internal and external factors. The fission yeast Schizosaccharomyces pombe may demonstrate catastrophic mitotic phenotypes due to mutations or drug treatments. One of the factors provoking catastrophic mitosis is a disturbed lipid metabolism, resulting from e.g. mutations in acetyl-CoA/biotin carboxylase (cut6), in fatty acid synthase (fas2/lsd1), or in the transcriptional regulator of lipid metabolism (cbf11) genes, as well as treatment with inhibitors of fatty acid synthesis. It was previously shown that mitotic fidelity in lipid metabolism mutants can be partially rescued by ammonium chloride. In this study we demonstrate that mitotic fidelity can be improved by multiple nitrogen sources. Moreover, this improvement is not limited to lipid metabolism disturbances but also applies to a number of unrelated mitotic mutants. Interestingly, the partial rescue is not achieved by restoring the lipid metabolism state, but rather indirectly. Our results highlight a novel role for nitrogen availability in mitotic fidelity.

Peripartal changes of metabolic and hormonal parameters in Romanian spotted cows and their relation with retained fetal membranes

This clinical study investigates various metabolic and physiological parameters in dairy cows during puerperium. Retained fetal membranes (RFM) is a significant postpartum complication that can affect the overall health, fertility and productivity of dairy cattle. The research focuses on changes in total proteins, albumin, glucose, triglycerides, total cholesterol, aspartate aminotransferase (AST) and alanine aminotransferase (ALT), cortisol, insulin, and insulin-like growth factor 1 (IGF-1) levels among cows experiencing normal post-partum period (NP) and those with RFM. A significant increase in protein levels was noted during the post-partum period in the RFM group, indicating physiological impacts of RFM at this stage. Albumin levels showed significant differences, highlighting a significant biological effect of RFM in the post-partum period. Glucose levels varied significantly in the weeks leading to parturition, suggesting altered metabolic states in cows that suffered RFM. Triglyceride and cholesterol levels were significantly higher during the antepartum period in the group that experienced reproductive failure, indicating substantial alterations in lipid metabolism which could herald the apparition of RFM. AST and ALT levels provided insights into cellular stress and liver function, with significant increases noted around parturition which could be attributed to the substantial physiological strain of parturition itself. Cortisol levels were higher in RFM cows 2 weeks before parturition, which could indicate an increasing stress response or a physiological preparation for the upcoming labor, and may be more pronounced in cows predisposed to RFM. Insulin levels decreased significantly before and at parturition in RFM cows, indicating a strong energy deficit. IGF-1 levels decreased significantly in RFM cows after parturition. Significant changes in metabolic parameters, such as glucose, triglycerides, and cholesterol levels, delineate the pronounced metabolic challenges faced by cows with RFM. The study elucidates that while some variations are noted as parturition approaches, the most substantial impacts attributable to RFM on metabolic and physiological parameters occur after parturition. These changes may have implications for the health, recovery, and productivity of cows postpartum, suggesting the need for targeted management strategies to mitigate the effects of RFM.

Differential reliance of CTD-nuclear envelope phosphatase 1 on its regulatory subunit in ER lipid synthesis and storage.

Lipin 1 is an ER enzyme that produces diacylglycerol, the lipid intermediate that feeds into the synthesis of glycerophospholipids for membrane expansion or triacylglycerol for storage into lipid droplets. CTD-Nuclear Envelope Phosphatase 1 (CTDNEP1) regulates lipin 1 to restrict ER membrane synthesis, but a role for CTDNEP1 in lipid storage in mammalian cells is not known. Here, we show that CTDNEP1 is reliant on its binding partner NEP1R1 for its stability and function in limiting ER expansion. CTDNEP1 contains an amphipathic helix at its N-terminus that targets to the ER, nuclear envelope and lipid droplets. We identify key residues at the binding interface of CTDNEP1 and NEP1R1 and show that they facilitate complex formation in vivo and in vitro. We demonstrate that NEP1R1 binding to CTDNEP1 shields CTDNEP1 from proteasomal degradation to regulate lipin 1 and restrict ER size. Unexpectedly, we found that NEP1R1 is not required for CTDNEP1's role in restricting lipid droplet biogenesis. Thus, the reliance of CTDNEP1 function on NEP1R1 depends on cellular demands for membrane production versus lipid storage. Together, our work provides a framework into understanding how the ER regulates lipid synthesis under different metabolic conditions.

Cardiac magnetic resonance reveals biventricular impairment in Cushing's syndrome: a multicentre case-control study.

Cushing's syndrome (CS) is associated with severe cardiovascular (CV) morbidity and mortality. Cardiac magnetic resonance (CMR) is the non-invasive gold standard for assessing cardiac structure and function; however, few CMR studies explore cardiac remodeling in patients exposed to chronic glucocorticoid (GC) excess. We aimed to describe the CMR features directly attributable to previous GC exposure in patients with cured or treated endogenous CS. This was a prospective, multicentre, case-control study enrolling consecutive patients with cured or treated CS and patients harboring non-functioning adrenal incidentalomas (NFAI), comparable in terms of sex, age, CV risk factors, and BMI. All patients were in stable condition and had a minimum 24-month follow-up. Sixteen patients with CS and 15 NFAI were enrolled. Indexed left ventricle (LV) end-systolic volume and LV mass were higher in patients with CS (p = 0.027; p = 0.013); similarly, indexed right ventricle (RV) end-diastolic and end-systolic volumes were higher in patients with CS compared to NFAI (p = 0.035; p = 0.006). Morphological alterations also affected cardiac function, as LV and RV ejection fractions decreased in patients with CS (p = 0.056; p = 0.044). CMR features were independent of metabolic status or other CV risk factors, with fasting glucose significantly lower in CS remission than NFAI (p < 0.001) and no differences in lipid levels or blood pressure. CS is associated with biventricular cardiac structural and functional impairment at CMR, likely attributable to chronic exposure to cortisol excess independently of known traditional risk factors.

The effect of soy isoflavones supplementation on metabolic status in patients with non-alcoholic fatty liver disease: a randomized placebo controlled clinical trial

BackgroundNon-alcoholic fatty liver disease (NAFLD) accounts as a crucial health concern with a huge burden on health and economic systems. The aim of this study is to evaluate the effect of soy isoflavones supplementation on metabolic status in patients with NAFLD.MethodsIn this randomized clinical trial, 50 patients with NAFLD were randomly allocated to either soy isoflavone or placebo groups for 12 weeks. The soy isoflavone group took 100 mg/d soy isoflavone and the placebo group took the similar tablets containing starch. Anthropometric indices, blood lipids, glycemic parameters and blood pressure were measured at the beginning and at the end of the study.ResultsAt the end of week 12 the level of serum triglyceride (TG), low density lipoprotein (LDL) and total cholesterol (TC) was significantly decreased only in soy isoflavone group compared to baseline (P < 0.05). Although waist circumference (WC) decreased significantly in both groups after 12 weeks of intervention (P < 0.05), hip circumference (HC) decreased significantly only in soy isoflavone group (P = 0.001). No significant changes observed regarding high density lipoprotein (HDL) and blood pressure in both groups. At the end of the study, serum glucose level was significantly decreased in the placebo group compared to baseline (P = 0.047). No significant changes demonstrated in the soy isoflavone group in regard to glycemic parameters (P > 0.05).ConclusionsThis study revealed that soy isoflavones could significantly reduce TG, LDL TC, WC and HC in NAFLD patients.Trial registrationThe Ethics committee of Ahvaz Jundishapur University of Medical Sciences approved the protocol of the present clinical research (IR.AJUMS.REC.1401.155). The study was in accordance with the Declaration of Helsinki. This study’s registered number and date are IRCT20220801055597N1 and 20.09.2022, respectively at https://fa.irct.ir.

Effects of Brown Seaweed (Ascophyllum nodosum) Supplementation on Enteric Methane Emissions, Metabolic Status and Milk Composition in Peak-Lactating Holstein Cows

The dairy industry contributes significantly to anthropogenic methane emissions, which have an impact on global warming. This study aimed to investigate the effects of a dietary inclusion of brown seaweed Ascophyllum nodosum on enteric methane emissions (EMEs), hematological and blood biochemical profiles, and milk composition in dairy cows. Eighteen Holstein cows were divided into three groups: CON (non-supplemented cows), BS50 (50 mL of 10% A. nodosum), and BS100 (100 mL of 10% A. nodosum). In each cow, measurements of EME, dry matter intake (DMI), and milk yield (MY), as well as blood and milk sampling with respective analyzes, were performed before supplementation (P1), after 15 (P2) days, and after 30 (P3) days of supplementation. A. nodosum reduced (p &lt; 0.05) methane production, methane yield, and methane intensity in both BS50 and BS100, and raised DMI (p &lt; 0.05) only in BS50. Total bilirubin (p &lt; 0.05) was higher in BS50 compared to CON cows in P2, and triacylglycerols were lower (p &lt; 0.05) in BS50 than in CON cows in P3. Higher milk fat content was found in BS50 than in CON cows in P3. C16:0 proportions were higher (p &lt; 0.05) in BS50 and BS100 than in CON cows, while C18:3n-3 was higher (p &lt; 0.05) in BS100 than in BS50 and CON cows in P3. Dietary treatment with A. nodosum reduced EMEs and showed the potential to increase DMI and to improve energy status as well as milk composition in peak-lactating dairy cows.

Inflammation subsequent to mild iron excess differentially alters regional brain iron metabolism, oxidation and neuroinflammation status in mice

Iron dyshomeostasis and neuroinflammation, characteristic features of the aged brain, and exacerbated in neurodegenerative disease, may induce oxidative stress-mediated neurodegeneration. In this study, the effects of potential priming with mild systemic iron injections on subsequent lipopolysaccharide (LPS)-induced inflammation in adult C57Bl/6J mice were examined. After cognitive testing, regional brain tissues were dissected for iron (metal) measurements by total reflection X-ray fluorescence and synchrotron radiation X-Ray fluorescence-based elemental mapping; and iron regulatory, ferroptosis-related, and glia-specific protein analysis, and lipid peroxidation by western blotting. Microglial morphology and astrogliosis were assessed by immunohistochemistry. Iron only treatment enhanced cognitive performance on the novel object location task compared with iron priming and subsequent LPS-induced inflammation. LPS-induced inflammation, with or without iron treatment, attenuated hippocampal heme oxygenase-1 and augmented 4-hydroxynonenal levels. Conversely, in the cortex, elevated ferritin light chain and xCT (light chain of System Xc−) were observed in response to LPS-induced inflammation, without and with iron-priming. Increased microglial branch/process lengths and astrocyte immunoreactivity were also increased by combined iron and LPS in both the hippocampus and cortex. Here, we demonstrate iron priming and subsequent LPS-induced inflammation led to iron dyshomeostasis, compromised antioxidant function, increased lipid peroxidation and altered neuroinflammatory state in a brain region-dependent manner.

Development of a bacterial cellulose-gelatin composite as a suitable scaffold for cardiac tissue engineering.

Cardiac tissue engineering is suggested as a promising approach to overcome problems associated with impaired myocardium. This is the first study to investigate the use of BC and gelatin for cardiomyocyte adhesion and growth. Bacterial cellulose (BC) membranes were produced by Komagataeibacter xylinus and coated or mixed with gelatin to make gelatin-coated BC (BCG) or gelatin-mixed BC (mBCG) scaffolds, respectively. BC based-scaffolds were characterized via SEM, FTIR, XRD, and AFM. Neonatal rat-ventricular cardiomyocytes (nr-vCMCs) were cultured on the scaffolds to check the capability of the composites for cardiomyocyte attachment, growth and expansion. The average nanofibrils diameter in all scaffolds was suitable (~ 30-65nm) for nr-vCMCs culture. Pore diameter (≥ 10µm), surface roughness (~ 182nm), elastic modulus (0.075 ± 0.015MPa) in mBCG were in accordance with cardiomyocyte requirements, so that mBCG could better support attachment of nr-vCMCs with high concentration of gelatin, and appropriate surface roughness. Also, it could better support growth and expansion of nr-vCMCs due to submicron scale of nanofibrils and proper elasticity (~ 0.075MPa). The viability of nr-vCMCs on BC and BCG scaffolds was very low even at day 2 of culture (~ ≤ 40%), but, mBCG could promote a metabolic active state of nr-vCMCs until day 7 (~ ≥ 50%). According to our results, mBCG scaffold was the most suitable composite for cardiomyocyte culture, regarding its physicochemical and cell characteristics. It is suggested that improvement in mBCG stability and cell attachment features may provide a convenient scaffold for cardiac tissue engineering.

Apelin-13 modulates the endometrial transcriptome of the domestic pig during implantation

BackgroundThe peri-implantation period is a critical time during pregnancy that mostly defines the overall litter size. Most authors agree that the highest percentage of embryo mortality occurs during this time. Despite the brevity of the peri-implantation period, it is the most dynamic part of pregnancy in which the sequential and uninterrupted course of several processes is essential to the animal’s reproductive success. Also then, the maternal uterine tissues undergo an intensive remodelling process, and their energy demand dramatically increases. It is believed that apelin, a member of the adipokine family, is involved in the control of female reproductive functions in response to the current metabolic state. The verified herein hypothesis assumed the modulatory effect of apelin on the endometrial tissue transcriptome on days 15 to 16 of gestation (beginning of implantation).ResultsThe analysis of data obtained during RNA-seq (Illumina HiSeq2500) of endometrial slices treated and untreated with apelin (n = 4 per group) revealed changes in the expression of 68 genes (39 up-regulated and 29 down-regulated in the presence of apelin), assigned to 240 gene ontology terms. We also revealed changes in the frequency of alternative splicing events (397 cases), as well as single nucleotide variants (1,818 cases) in the presence of the adipokine. The identified genes were associated, among others, with the composition of the extracellular matrix, apoptosis, and angiogenesis.ConclusionsThe obtained results indicate a potential role of apelin in the regulation of uterine tissue remodelling during the peri-implantation period.