Transferrin Research Articles

Evaluation of Iron Status in Cats With Hypertrophic Cardiomyopathy With and Without Congestive Heart Failure

Background: All organisms need iron for their survival and metabolic activity, and the healing process of patients depends on this element. Hence, its deficiency can negatively affect patients’ quality of life and cause disorders. Although iron deficiency is proven an important comorbidity in human and canine patients with heart failure, no research has been published on the role of iron in feline hypertrophic cardiomyopathy. Objectives: This research aimed to determine and compare the iron status of cats with hypertrophic cardiomyopathy with and without congestive heart failure. Methods: Based on laboratory, radiographic, and echocardiographic findings, 45 client-owned cats were studied and divided into three groups: control, hypertrophic cardiomyopathy (HCM) without congestive heart failure, and hypertrophic cardiomyopathy with congestive heart failure. Iron and ferritin concentrations, total iron-binding capacity (TIBC), and serum transferrin saturation (TSAT) percentage were measured and compared in all cats. Statistical nonparametric testing was used to analyze the data. Results: No groups illustrate any statistically significant difference for iron concentration (P=0.3), ferritin concentration (P=0.853), TIBC (P=0.1), and TSAT (P=0.639). The highest iron concentration and the lowest transferrin level and the transferrin saturation percentage were observed in the HCM group with congestive heart failure. Also, cats without congestive heart failure had the lowest TIBC compared to other groups. Conclusion: Unlike previous studies in dogs and humans, our study did not show a significant difference between cats with hypertrophic cardiomyopathy regarding iron status.

In-depth urinary and exosome proteome profiling analysis identifies novel biomarkers for diabetic kidney disease.

Diabetic kidney disease (DKD) is a major microvascular complication of type 2 diabetes mellitus (T2DM). Monitoring the early diagnostic period and disease progression plays a crucial role in treating DKD. In this study, to comprehensively elucidate the molecular characteristics of urinary proteins and urinary exosome proteins in type 2 DKD, we performed large-scale urinary proteomics (n=144) and urinary exosome proteomics (n=44) analyses on T2DM patients with albuminuria in varying degrees. The dynamics analysis of the urinary and exosome proteomes in our study provides a valuable resource for discovering potential urinary biomarkers in patients with DKD. A series of potential biomarkers, such as SERPINA1 and transferrin (TF), were detected and validated to be used for DKD diagnosis or disease monitoring. The results of our study comprehensively elucidated the changes in the urinary proteome and revealed several potential biomarkers reflecting the progression of DKD, which provide a reference for DKD biomarker screening.

The use of iron-containing drugs for the prevention of alimentary anemia in sows and their offspring

As a result of a scientific and economic experiment conducted in the conditions of the industrial pig complex of Bryansk Meat Processing Plant LLC in Vygonichi district, the effectiveness of the use of iron–containing preparations Ferrolong and Ferzaks-forte for the prevention of alimentary anemia of pregnant sows and piglets was studied. The object of the study was pregnant sows of a large white breed with an average live weight of 150-160 kg at the age of two years, and piglets obtained from them. At the first stage of the research, two groups of sows were formed, 3 heads each. 15 days before farrowing, the sows of the experimental group received the drug Ferrolong (iron content III 200 mg/ml, vitamin B12 - 0.1 mg/ml) at a dose of 4 ml intramuscularly. Sows of the control group did not receive injections of iron-containing preparations.The effect of the drugs on the growth and safety of piglets, on biochemical (iron, total iron binding capacity of serum (OHSS), % saturation of transferrin) and hematological parameters was analyzed. Based on the conducted step-by-step studies, it was found that the introduction of Ferrolong 15 days before farrowing stimulates hematopoiesis in sows, but does not significantly affect the red blood indicators of suckling piglets. Intramuscular administration of Ferrolong to piglets at a dose of 1 ml in the first three days of life is accompanied by a pronounced antianemic effect, and is characterized by a high content of hemoglobin in erythrocytes and a saturation coefficient of serum transferrin. This scheme is recommended for the prevention of iron deficiency anemia in the household. Ferzaks-forte, due to its vitamins, has a broader effect on metabolic processes, but laboratory indicators indicate that a single intramuscular injection of this drug is not enough to prevent anemia.

Gastric Glandular Siderosis but not Lamina Propria Siderosis is Associated With High Serum Ferritin Levels.

Three histologic patterns of gastric siderosis (GS) are described: pattern A (predominantly in lamina propria stromal cells-gastric lamina propria siderosis [GLPS]), pattern B (mostly extracellular crystalline iron) and pattern C (predominantly in glandular epithelium-gastric glandular siderosis [GGS]). This study aimed to analyze the association of GGS with clinicopathologic features using 3 cohorts. Cohort #1 consisted of 76 gastric siderosis cases. Upon classifying the cases into 3 groups by percentage of glandular involvement (negative, 1% to 5%, ≥5% GGS), the degree of GGS was positively associated with serum ferritin levels ( P =0.002), transferrin saturation ( P =0.003), and history of blood transfusion ( P =0.009). After excluding cases with coarse extracellular crystalline iron, cohort #1 was reclassified into 3 groups by degree of GLPS (no, rare [discernible at ×20 or ×40], overt [readily visible at low power]). The degree of GLPS was positively correlated with oral iron pill use ( P =0.01), but not serum ferritin levels or transferrin saturation. Cohort #2 contained 31 gastric samples from patients with hereditary hemochromatosis, most received phlebotomy treatment. GGS was identified in 2 (6.4%) patients; both had high ferritin levels. Cohort #3 included 38 gastric samples from patients with cirrhosis. Three (8%) cases showed GGS; serum ferritin level was available for 1 case and was elevated. These results indicate that GGS is associated with systemic iron overload, while GLPS is correlated with oral iron pill use. The identification of GGS, especially when it's ≥5%, should trigger further workup for potential systemic iron overload and underlying etiologies.

Iron homeostasis in full-term, normal birthweight Gambian neonates over the first week of life

Human neonates elicit a profound hypoferremia which may protect against bacterial sepsis. We examined the transience of this hypoferremia by measuring iron and its chaperone proteins, inflammatory and haematological parameters over the first post-partum week. We prospectively studied term, normal weight Gambian newborns. Umbilical cord vein and artery, and serial venous blood samples up to day 7 were collected. Hepcidin, serum iron, transferrin, transferrin saturation, haptoglobin, c-reactive protein, α1-acid-glycoprotein, soluble transferrin receptor, ferritin, unbound iron-binding capacity and full blood count were assayed. In 278 neonates we confirmed the profound early postnatal decrease in serum iron (22.7 ± 7.0 µmol/L at birth to 7.3 ± 4.6 µmol/L during the first 6–24 h after birth) and transferrin saturation (50.2 ± 16.7% to 14.4 ± 6.1%). Both variables increased steadily to reach 16.5 ± 3.9 µmol/L and 36.6 ± 9.2% at day 7. Hepcidin increased rapidly during the first 24 h of life (19.4 ± 14.4 ng/ml to 38.9 ± 23.9 ng/ml) and then dipped (32.7 ± 18.4 ng/ml) before rising again at one week after birth (45.2 ± 19.1 ng/ml). Inflammatory markers increased during the first week of life. The acute postnatal hypoferremia in human neonates on the first day of life is highly reproducible but transient. The rise in serum iron during the first week of life occurs despite very high hepcidin levels indicating partial hepcidin resistance.Trial Registration: clinicaltrials.gov (NCT03353051). Registration date: November 27, 2017.

Persistent Increase in Serum Ferritin Levels despite Converting to Permanent Vascular Access in Pediatric Hemodialysis Patients: Pediatric Nephrology Research Consortium Study.

Our objective was to examine serum ferritin trends after conversion to permanent vascular access (PVA) among children who started hemodialysis (HD) using tunneled cuffed catheters (TCC). Retrospective chart reviews were completed on 98 subjects from 20 pediatric HD centers. Serum ferritin levels were collected at the creation of PVA and for two years thereafter. There were 11 (11%) arteriovenous grafts (AVG) and 87 (89%) arteriovenous fistulae (AVF). Their mean TCC use was 10.4 ± 17.3 months. Serum ferritin at PVA creation was elevated at 562.64 ± 492.34 ng/mL, increased to 753.84 ± 561.54 ng/mL (p = < 0.001) in the first year and remained at 759.60 ± 528.11 ng/mL in the second year (p = 0.004). The serum ferritin levels did not show a statistically significant linear association with respective serum hematocrit values. In a multiple linear regression model, there were three predictors of serum ferritin during the first year of follow-up: steroid-resistant nephrotic syndrome as primary etiology (p = 0.035), being from a center that enrolled >10 cases (p = 0.049) and baseline serum ferritin level (p = 0.017). Increasing serum ferritin after conversion to PVA is concerning. This increase is not associated with serum hematocrit trends. Future studies should investigate the correlation of serum transferrin saturation and ferritin levels in pediatric HD patients.

Iron status and cardiometabolic risk in children

AimWe aimed to evaluate associations between serum ferritin and transferrin and variables related to the metabolic syndrome (MetS) in children. MethodsCross-sectional and longitudinal study in prepubertal children (n = 832) aged 3–14 years. A subset (n = 203) were re-examined after a mean follow-up of 3.7 ± 0.8 years[range 2–6]. Outcomes were MetS and MetS components scores, glycosylated haemoglobin (HbA1c), and their follow-up change. ResultsChildren with low ferritin had increased HbA1c Z scores (ANCOVA, P = 0.003). Ferritin was inversely associated with glycaemia [fully adjusted β (95% confidence interval): −2.35(−4.36 to −0.34)]. Transferrin was associated with diastolic blood pressure [β: 0.02(0.01–0.04)] and log-HOMA-IR [β:0.001(0.0005–0.002)]. MetS risk score worsened during follow-up in children with the lowest baseline ferritin levels. In contrast, at baseline ferritin was positively associated with all (except glycaemia) the MetS-related variables but adjustments for inflammatory, hepatic function, and body mass markers attenuated those associations (P > 0.05). ConclusionsLower iron status was independently associated with glycaemic markers and MetS in children, whereas higher ferritin levels were related to other cardiometabolic risk markers under the influence of inflammation, hepatic injury and body mass. Research is required to study whether this mixed pattern is part of an early risk or would be explained by a normal transition during growth and development.

#2518 EFFECT OF VACCINATION ON OXIDANT/ANTIOXIDANT STATUS IN HEMODIALYSIS PATIENTS WITH POST-COVID CONDITIONS

Abstract Background and Aims Hemodialysis (HD) patients are at high risk for post-COVID conditions and a high mortality rate over a 1-year period after diagnosis of COVID-19, especially in the first 3 months. Evidence shows that vaccinated individuals who experience breakthrough infection are less likely to report post-COVID conditions compared with unvaccinated individuals. Although oxidative stress has been shown to be an important cause of post-COVID conditions, there is a general lack of data on oxidant/antioxidant status in HD patients with post-COVID conditions. The present study aimed to evaluate the oxidant/antioxidant markers in HD patients with post-COVID conditions according to vaccination status. Method A total of 106 HD patients, aged 52.4 ± 10.2 years, and dialysis vintage of 68 (29-134) months, were enrolled in this cross-sectional observational cohort study. Patients were divided into 3 groups according to their vaccination status and the presence of post-COVID conditions. Group 1 consisted of 36 HD patients who had been fully vaccinated against COVID-19 with either Pfizer-BNT-162b2 or Moderna-mRNA-1273 vaccine and had experienced a post-vaccination SARS-CoV-2 infection and had at least 1 post-COVID symptom. Group 2 consisted of 35 fully vaccinated HD patients who had never been infected with COVID-19 (vaccinated control group), and Group 3 included 35 unvaccinated HD patients who had experienced COVID-19 and had post-COVID conditions (unvaccinated control group). Concentrations of malondialdehyde in serum (MDAs) and erythrocytes (MDAe), sulfhydryl groups (SH-groups), serum catalase activity (CTs), serum transferrin and ceruloplasmin levels were determined 3 months after COVID -19 recovery. Data were expressed as a median and interquartile range [Me (Q25-Q75)] and compared with the Kruskal-Wallis test. Results The vaccinated HD patients with post-COVID conditions had the highest concentrations of MDAs and ceruloplasmin, and lower serum levels of CTs and transferrin compared with the vaccinated and unvaccinated control groups (Table 1). Conclusion Our findings suggest a significant oxidative imbalance in HD patients with post-COVID syndrome most likely due to the synergistic effects of the virus and the vaccine. The use of antioxidant supplements might be a possible strategy to treat post-COVID conditions in HD patients.

#4296 EFFECTS OF FERRIC CITRATE HYDRATE ON FIBROBLAST GROWTH FACTOR 23 AND PLATELET COUNT IN CKD AND NON-CKD PATIENTS WITH IRON DEFICIENCY ANAEMIA

Abstract Background and Aims Iron deficiency increases the transcription and cleavage of the peptide hormone, fibroblast growth factor 23(FGF23). Elevated FGF23 has been associated with increased risk of cardiovascular events and mortality. Iron deficiency also increases platelet count (PLT) in part, and higher levels PLT are associated with arterial thrombosis in the brain. Ferric citrate hydrate (FC, Riona®, Torii Pharmaceutical Co., Ltd. Tokyo, Japan) is an oral iron-based phosphate binder for patients with chronic kidney disease (CKD) and also an iron preparation approved for treatment of iron deficiency anaemia (IDA) in Japan. A phase 3 study was conducted to investigate the efficacy and safety of FC in CKD and non-CKD patients with IDA. This study aimed to evaluate the effects of FC on intact FGF23 and c-terminal FGF23 levels, and the proportion of patients with high PLT (exceeding upper limit: &amp;gt;35.2 × 104/µL). Method A randomized, open-label, multicentre, uncontrolled, 24-week study was conducted at 31 centres in Japan from July 2018 to December 2019 (JapicCTI-184000) in CKD and non-CKD patients with IDA (Hb: ≥8.0 g/dL and &amp;lt;11.0 g/dL, serum ferritin &amp;lt;50 ng/mL in CKD (eGFRcre &amp;lt;60 mL/min/1.73 m2) and &amp;lt;12 ng/mL in non-CKD). CKD patients scheduled to initiate maintenance dialysis were excluded. Dynamic allocation was used to randomise subjects (CKD and non-CKD with Hb at baseline) to the FC-low group (500 mg [approximately 120 mg elemental iron]/day) or FC-high group (1000 mg [approximately 240 mg elemental iron]/day) (1:1). Notably, if investigators determined that sufficient iron replacement had been achieved from week 8 onwards, the study treatment was completed. For this reason, changes from baseline to week 8 were evaluated. Results Of 73 patients (CKD n = 42, non-CKD n = 31), 36 were allocated to the FC-low group (CKD n = 21, non-CKD n = 15) and 37 to the FC-high group (CKD n = 21, non-CKD n = 16). Baseline levels of serum ferritin, transferrin saturation (TSAT), c-terminal FGF23, intact FGF23, and PLT are shown in Table 1. Regardless of CKD status, serum ferritin and TSAT increased. After FC-low treatment, mean changes from baseline to week 8 (95% CI) in serum ferritin and TSAT were 18.8 (13.3, 24.2) ng/mL and 8.1 (4.4, 11.8) % in CKD, 17.5 (13.8, 21.3) ng/mL and 13.8 (8.7, 18.9) % in non-CKD;, they were 28.1 (13.4, 42.7) ng/mL and 8.8 (5.4, 12.1) % in CKD, 15.9 (12.1, 19.8) ng/mL and 19.9 (9.8, 30.1) % in non-CKD. After administration of FC, in both groups, intact FGF23 levels did not change, whereas c-terminal FGF23 levels decreased. Median changes (interquartile range) from baseline to week 8 of c-terminal FGF23 were -58.00 (-227.50, -12.25) RU/mL in CKD and -725.00 (-1124.00, -168.50) RU/mL in non-CKD, and -66.00 (-265.70, -27.00) RU/mL in CKD and -649.50 (-1127.00, -326.65) RU/mL in non-CKD. Serum phosphate did not change regardless of CKD status. At baseline, high PLT was observed in the FC-low group in 1 CKD case (5.0%) and 8 non-CKD cases (53.3%), and in the FC-high group in 3 CKD cases (15.8%) and 8 non-CKD cases (50.0%). In all these patients, PLT reduction to below 35.2 × 104/µL was observed until week 8. Conclusion In patients with IDA, administration of FC increased serum ferritin and TSAT, decreased c-terminal FGF23, and normalized PLT in patients with high PLT at baseline regardless of CKD status. FC may decrease the potential risk of cardiovascular events in CKD or non-CKD patients with IDA.

#6822 ANALYSIS OF IRON STATUS AND ITS INFLUENCING FACTORS IN INITIAL PERITONEAL DIALYSIS PATIENTS

Abstract Background and Aims Iron deficiency (ID) is an important cause of poor response to anemia treatment in dialysis patients. The initial status of iron metabolism in uremic patients when they enter peritoneal dialysis (PD) may affect the strategy of iron therapy. Therefore, we investigated and analyzed the initial iron indicator levels and ID in patients with end-stage renal disease undergoing continuous ambulatory peritoneal dialysis (CAPD), and discussed the possible influencing factors of ID and iron supplementation treatment strategies. Method The clinical data of patients who underwent PD for 1–3months in West China Hospital, Sichuan University from January, 2011 to January, 2018 were collected. The clinical data including patients' characteristics, medication (oral iron supplement and erythropoietin), iron indicators [ferritin, serum iron, serum iron saturation (TSAT) and transferrin], hemoglobin (HB), serum albumin (Alb), blood lipids, C-reactive protein and IL-6, β2-microglobulin, electrolytes and other biochemical indicators, as well as PD-related parameters. ID or relative ID was defined as ferritin &amp;lt; = 100 ng/ml or TSAT &amp;lt; = 20%, and absolute ID was defined as ferritin &amp;lt; = 100 ng/ml and TSAT &amp;lt; = 20%. Person correlation and Spearman correlation were used for normal distribution and non-normal distribution measurement data, respectively. Kendall correlation was used for categorical variables. Multivariate linear regression was used to analyze the independent influencing factors of ferritin and transferrin saturation. Binary logistic regression was used to analyze the independent influencing factors of ID. Results A total of 633 adult patients with stable condition and complete iron metabolism data were enrolled. The mean age was 45.7±14.0 years (18-91 years). There were 397 males (61.1%) and 100 patients (15.8%) with diabetes. The mean HB level was 95.4±18.4g/L, the ferritin level was 277.9±278.1ng/ml, the TSAT 29.9±12.9%, and the transferrin level 1.89±0.4 g/L. Among them, 487 (76.9%) used oral iron therapy and 412 (65.1%) used erythropoietin. 156 (58.8%) had HB less than 100g/L, and 156 (44.2%) had ID. There were 32.2% patients with ferritin &amp;lt;100 ng/mL and 23.4% patients with TSAT&amp;lt;20%. Among patients who used oral iron therapy, 16.2% had absolute ID and 39.6% relative ID. there was no correlation between ID and diabetes, cardiovascular disease, gender, age, Alb, high-sensitivity CRP, IL-6, most of electrolytes, β2 microglobulin, blood leukocyte count, dialysate serum creatinine ratio at 4 hours, D/P Cr(4h), and there was no correlation between ID and eGFR (p = 0.057). Serum magnesium level (r = -0.414, p&amp;lt;0.001), body surface area (r = -0.112, p = 0.005) and triglyceride (r = -0.086, p = 0.03) were negatively correlated with ID. Transferrin level (r = 0.427, p&amp;lt;0.001) and platelet count (r = 0.169, p&amp;lt;0.001) were positively correlated with ID. Multiple linear regression analysis with serum magnesium, body surface area, triglyceride, platelet count and eGFR input showed that triglyceride (p = 0.001), body surface area (p = 0.05) and platelet count (p = 0.001) were independently correlated with ferritin. With transferrin saturation as the dependent variable, showed that only platelet count (p&amp;lt;0.001) was independently associated with transferrin saturation. Binary logistic regression analysis model (dependent variable being presence of ID = 1) showed that body surface area (β = -1.055, p = 0.042), triglyceride (β = -0.295, p = 0.014), serum magnesium (β = 0.997, p = 0.040) and platelet count (β = -0.006, p = 0.014). p&amp;lt;0.001) were independently associated with ID Conclusion ID is common in new PD patients in our hospital, with a ferritin level of less than 100 ng/mL in one-third of patients. Platelet counts were higher in ID patients. People with larger body surface area and higher triglyceride levels may have more iron stores. Our study showed new PD patients should pay attention to iron supplementation before and after PD catheterization. Intravenous iron supplementation should be considered in time for those who still have ID after oral iron supplementation. In addition, increased platelet count may predict the occurrence of ID anemia.

Clinical and Echocardiographic Correlates of Iron Status in Chronic Heart Failure Patients: A Cross-Sectional Descriptive Study.

Chronic heart failure (HF) is one of the conditions commonly seen in the medical outpatient departments, and iron deficiency (ID) has been reported as the commonest nutritional deficiency in these patients. The presence of ID may interfere with the clinical parameters of chronic HF. The relationship between iron status and chronic HF needs more attention and should be given more consideration in the evaluation of patients with chronic HF. The aim of the study was to determine the relationship, if any, between iron status and clinical/echocardiographic variables in chronic HF. A cross-sectional descriptive study was carried out at the Lagos University Teaching Hospital (LUTH), Nigeria, where 88 patients with chronic HF were recruited to participate in this study. The participants underwent clinical and laboratory assessments. Iron status was assessed with full blood count parameters; serum ferritin and transferrin saturation (Tsat) and its relationship with clinical parameters among these participants were also studied. No correlations existed between the duration of chronic HF and iron status when compared using Tsat. However, a significant weak negative correlation was observed between the duration of HF and the serum ferritin levels. The clinical characteristics of the HF participants with and without ID were compared. There was no significant difference in the frequency of prior hospitalization in both groups. However, a higher proportion of participants with severe HF (New York Heart Association (NYHA) classes III/IV) (n = 14; 46.7%) were iron-deficient compared to those with moderate chronic HF (NYHA II) (n = 11; 36.7%). This relationship was statistically significant. Left ventricular ejection fraction (LVEF) was similar in the iron-deficient and iron-replete groups (using serum ferritin or Tsat) both when compared as means and when compared after categorizing LVEF as HF with preserved ejection fraction (HFpEF) vs HF with reduced ejection fraction (HFrEF). There was no statistically significant correlation between the severity of ID and LVEF. Conclusion: A spectrum of clinical changes occurs in patients with chronic HF. ID can make these changes more profound and the condition less amenable to standard HF treatments. These patients may therefore benefit from further evaluation for this nutritional deficiency. Laboratory measurements including Tsat and serum ferritin may help in further assessment of select patients with worse and/or non-responsiveclinical parameters.

Canonical BAF complex activity shapes the enhancer landscape that licenses CD8+ T cell effector and memory fates

CD8+ Tcells provide host protection against pathogens by differentiating into distinct effector and memory cell subsets, but how chromatin is site-specifically remodeled during their differentiation is unclear. Due to its critical role in regulating chromatin and enhancer accessibility through its nucleosome remodeling activities, we investigated the role of the canonical BAF (cBAF) chromatin remodeling complex in antiviral CD8+ Tcells during infection. ARID1A, a subunit of cBAF, was recruited early after activation and established de novo open chromatin regions (OCRs) at enhancers. Arid1a deficiency impaired the opening of thousands of activation-induced enhancers, leading to loss of TF binding, dysregulated proliferation and gene expression, and failure to undergo terminal effector differentiation. Although Arid1a was dispensable for circulating memory cell formation, tissue-resident memory (Trm) formation was strongly impaired. Thus, cBAF governs the enhancer landscape of activated CD8+ Tcells that orchestrates TF recruitment and activity and the acquisition of specific effector and memory differentiation states.

Characterization of CRISPR/Cas9-edited human placental allogenic stromal cells with low tissue factor expression and reduced thrombotic effects

The tissue factor (TF/CD142) expressed by mesenchymal stromal cells (MSCs) has been regarded as a safety concern in clinical applications as it may trigger thrombosis when MSCs administered intravenously. Human placental allogenic stromal cells (ASCs) are culture-expanded, undifferentiated MSC-like cells derived from full-term postpartum placenta and possess immunomodulatory and pro-angiogenic activities, however, express TF. Here we performed CRISPR/Cas9-mediated TF gene knock out (TFKO) in ASCs, leading to significantly lower TF expression, activity and thrombotic effects. ASCs’ characteristics including expansion, expression of phenotypic markers and secretory profile remained unchanged in edited cells, and their immunomodulatory activities, which are functionally relevant to therapeutic applications, were not affected upon TFKO. Taken together, this study provides a feasible strategy which could improve the clinical safety features of MSC-based cell therapy by CRISRP/Cas9-mediated TF gene knock out.

Comparative Study of Isoflavone Synthesis Genes in Two Wild Soybean Varieties Using Transcriptomic Analysis

Soybean is an important food crop that contains high amounts of isoflavones. However, due to the expression of multiple genes, different soybean seeds have different isoflavone compositions. The underlying mechanisms for this complexity remain unknown. In this study, we identified potential differentially expressed genes (DEGs) in two wild soybean cultivars, ZYD7068 (high isoflavone) and ZYD7194 (low isoflavone), at different seed developmental stages using RNA-seq technology and compared their differences in isoflavone content. A total of 1067 and 6479 differentially metabolized genes were identified at R6 and R8 stages, respectively. Subsequent analysis of the KEGG pathway revealed that three of these differential metabolized genes were involved in the Isoflavonoid biosynthesis and Flavone and flavonol biosynthesis at the R6 stage. A total of 80 TF genes encoding differential expression of MYB, bZIP, and WRKY were identified in A1 vs. B1 and A3 vs. B3. Eight differentially expressed genes were identified in duplicates at both stages, and three genes showed the same expression trend at both stages. To confirm the results of RNA-seq, qRT-PCR was performed to analyze the expression of the six identified differentially expressed genes (DEGs). The results of qRT-PCR were consistent with the results of RNA-seq. We found that four genes (Glyma.13G173300, Glyma.13G173600, Glyma.14G103100, and Glyma.17G158900) may be involved in the positive regulation of isoflavone synthesis, while two genes (Glyma.04G036700 and Glyma.19G030500) may be involved in the negative regulation of isoflavone synthesis. These findings suggest that the observed difference in isoflavone levels between the two cultivars may be attributable to the differential expression of these six genes at later stages of seed development.

Dietary replacement of inorganic trace minerals with lower levels of organic trace minerals leads to enhanced antioxidant capacity, nutrient digestibility, and reduced fecal mineral excretion in growing-finishing pigs.

More effective and environment-friendly organic trace minerals have great potential to replace the inorganic elements in the diets of livestock. This study aimed to investigate the effects of dietary replacement of 100% inorganic trace minerals (ITMs) with 30-60% organic trace minerals (OTMs) on the performance, meat quality, antioxidant capacity, nutrient digestibility, and fecal mineral excretion and to assess whether low-dose OTMs could replace whole ITMs in growing-finishing pigs' diets. A total of 72 growing-finishing pigs (Duroc × Landrace × Yorkshire) with an initial average body weight of 74.25 ± 0.41 kg were selected and divided into four groups with six replicates per group and three pigs per replicate. The pigs were fed either a corn-soybean meal basal diet containing commercial levels of 100% ITMs or a basal diet with 30, 45, or 60% amino acid-chelated trace minerals instead of 100% ITMs, respectively. The trial ended when the pigs' weight reached ~110 kg. The results showed that replacing 100% ITMs with 30-60% OTMs had no adverse effect on average daily gain, average daily feed intake, feed/gain, carcass traits, or meat quality (P > 0.05) but significantly increased serum transferrin and calcium contents (P < 0.05). Meanwhile, replacing 100% ITMs with OTMs tended to increase serum T-SOD activity (0.05 ≤ P < 0.1), and 30% OTMs significantly increased muscle Mn-SOD activity (P < 0.05). Moreover, replacing 100% ITMs with OTMs tended to increase the apparent digestibility of energy, dry matter, and crude protein (0.05 ≤ P < 0.1) while significantly reducing the contents of copper, zinc, and manganese in feces (P < 0.05). In conclusion, dietary supplementation with 30-60% OTMs has the potential to replace 100% ITMs for improving antioxidant capacity and nutrient digestibility and for reducing fecal mineral excretion without compromising the performance of growing-finishing pigs.

Assessing Iron Status in Chronic Heart Failure Patients by Using Serum Ferritin and Transferrin Saturation Levels: A Cross-Sectional Descriptive Study.

Background and objective Chronic heart failure (HF) is a major medical condition worldwide and is associatedwith significant morbidity and mortality. Chronic HF could be complicated by iron deficiency (ID), and in severe cases, ID anemia, leading to negative HF outcomes even in people on optimal HF treatments. IDhas been reported to be the most common nutritional deficiency in chronic HF. It is therefore important to study and analyze the relationship between these two variables. Identifying and treating the comorbidity of ID in chronic HF may helpimprove the treatment outcomes of chronic HF. In this study, we aimed to determine the iron status of chronic HF patients by using serum ferritin (SF) and transferrin saturation (TSAT). Materials and methods A cross-sectional descriptive study was conducted involving 88 Nigerian patients with chronic HF at the Lagos University Teaching Hospital (LUTH). The participants were evaluated based on their laboratory findings. Results ID was found in 34% of chronic HF patients. Of them, 17% had absolute ID while 17% had functional ID. Conclusion ID was present in about one-third of the chronic HF patients. It was more common and worse in patients belonging to advanced HF functional classes.

De Novo Transcriptome Profiling for the Generation and Validation of Microsatellite Markers, Transcription Factors, and Database Development for Andrographis paniculata.

Andrographis paniculata belongs to the family Acanthaceae and is known for its medicinal properties owing to the presence of unique constituents belonging to the lactones, diterpenoids, diterpene glycosides, flavonoids, and flavonoid glycosides groups of chemicals. Andrographolide, a major therapeutic constituent of A. paniculata, is extracted primarily from the leaves of this plant and exhibits antimicrobial and anti-inflammatory activities. Using 454 GS-FLX pyrosequencing, we have generated a whole transcriptome profile of entire leaves of A. paniculata. A total of 22,402 high-quality transcripts were generated, with an average transcript length and N50 of 884 bp and 1007 bp, respectively. Functional annotation revealed that 19,264 (86%) of the total transcripts showed significant similarity with the NCBI-Nr database and were successfully annotated. Out of the 19,264 BLAST hits, 17,623 transcripts were assigned GO terms and distributed into three major functional categories: molecular function (44.62%), biological processes (29.19%), and cellular component (26.18%) based on BLAST2GO. Transcription factor analysis showed 6669 transcripts, belonging to 57 different transcription factor families. Fifteen TF genes that belong to the NAC, MYB, and bHLH TF categories were validated by RT PCR amplification. In silico analysis of gene families involved in the synthesis of biochemical compounds having medicinal values, such as cytochrome p450, protein kinases, heat shock proteins, and transporters, was completed and a total of 102 different transcripts encoding enzymes involved in the biosynthesis of terpenoids were predicted. Out of these, 33 transcripts belonged to terpenoid backbone biosynthesis. This study also identified 4254 EST-SSRs from 3661 transcripts, representing 16.34% of the total transcripts. Fifty-three novel EST-SSR markers generated from our EST dataset were used to assess the genetic diversity among eighteen A. paniculata accessions. The genetic diversity analysis revealed two distinct sub-clusters and all accessions based on the genetic similarity index were distinct from each other. A database based on EST transcripts, EST-SSR markers, and transcription factors has been developed using data generated from the present study combined with available transcriptomic resources from a public database using Meta transcriptome analysis to make genomic resources available in one place to the researchers working on this medicinal plant.

A Novel NanoMIP-SPR Sensor for the Point-of-Care Diagnosis of Breast Cancer.

Simple, fast, selective, and reliable detection of human epidermal growth factor receptor 2 (HER2) is of utmost importance in the early diagnosis of breast cancer to prevent its high prevalence and mortality. Molecularly imprinted polymers (MIPs), also known as artificial antibodies, have recently been used as a specific tool in cancer diagnosis and therapy. In this study, a miniaturized surface plasmon resonance (SPR)-based sensor was developed using epitope-mediated HER2-nanoMIPs. The nanoMIP receptors were characterized using dynamic light scattering (DLS), zeta potential, Fourier-transform infrared spectroscopy (FT-IR), transmission electron microscopy (TEM), energy-dispersive X-ray spectroscopy (EDX), and fluorescent microscopy. The average size of the nanoMIPs was determined to be 67.5 ± 12.5 nm. The proposed novel SPR sensor provided superior selectivity to HER2 with a detection limit (LOD) of 11.6 pg mL-1 in human serum. The high specificity of the sensor was confirmed by cross-reactivity studies using P53, human serum albumin (HSA), transferrin, and glucose. The sensor preparation steps were successfully characterized by employing cyclic and square wave voltammetry. The nanoMIP-SPR sensor demonstrates great potential for use in the early diagnosis of breast cancer as a robust tool with high sensitivity, selectivity, and specificity.

Dairy Milk Protein-Derived Bioactive Peptides: Avengers Against Metabolic Syndrome.

Metabolic syndrome is continuously increasing among the world's populations. Metabolic syndrome is a medical condition in which individuals suffer from high blood pressure, high blood glucose levels, and obesity. The in vitro and in vivo bioactivities of dairy milk protein-derived peptides (MPDP) have proven their potential as an excellent natural alternative to the current medical treatment for metabolic syndrome. In this context, the review discussed the major protein source of dairy milk and provides current knowledge on the novel and integrated approach to MPDP production. A detailed comprehensive discussion is provided on the current state of knowledge regarding the in vitro and in vivo bioactivities of MPDP against metabolic syndrome. In addition, the most important aspect of digestive stability, allergenicity, and further directions for MPDP application is provided. The major proteins found in milk are casein and whey, while a minor portion of serum albumin and transferrin are reported. Upon gastrointestinal digestion or enzymatic hydrolysis, these proteins produce peptides with various biological activities including antioxidative, antiinflammatory, antihypertensive, antidiabetic, and antihypercholesterolemic, which could help in ameliorating metabolic syndrome. Bioactive MPDP has the potential to curtail metabolic syndrome and potentially act as a safe replacement for chemical drugs with fewer side effects.

Functionalized pyrite nanozyme probe and imprinted polymer modified with hydrophilic layer for rapid colorimetric analysis of glycoprotein in serum

The biological molecules used in the sandwich detection method have problems such as complex extraction processes, high costs, and uneven quality. Therefore we integrated glycoprotein molecularly controllable-oriented surface imprinted magnetic nanoparticles (GMC-OSIMN) and boric acid functionalized pyrite nanozyme probe (BPNP) to replace the traditional antibody and horseradish peroxidase for sensitive detection of glycoproteins through sandwich detection.In this work, a novel nanozyme functionalized with boric acid was used to label glycoproteins that were captured by GMC-OSIMN. The substrate in the working solution catalyzed by the nanozyme labeled on the protein underwent visible color changes to the naked eye, and the generated signal can be quantitatively detected by a spectrophotometer, and the best color development conditions of the novel nanozyme under the influence of many factors were determined through multi-dimensional investigation. The optimum conditions of sandwich are optimized with ovalbumin (OVA), and it was extended to the detection of transferrin (TRF) and alkaline phosphatase (ALP) in the application. The detection range for TRF was 2.0 × 10−1-1.0 × 104 ng mL−1 with a detection limit of 1.32 × 10−1 ng mL−1, The detection range for ALP was 2.0 × 10−3-1.0 × 102 U L−1 with the detection limit of 1.76 × 10−3 U L−1. This method was subsequently used to detect TRF and ALP levels in 16 liver cancer patients, and the standard deviation of the test results of each patient was less than 5.7%.