Neopterin Research Articles

Biomarker relationships with small bowel histopathology among malnourished children with environmental enteric dysfunction in a multicountry cohort study

BackgroundValidated biomarkers could catalyze environmental enteric dysfunction (EED) research. ObjectivesLeveraging an EED histology scoring system, this multicountry analysis examined biomarker associations with duodenal histology features among children with EED. We also examined differences in 2-h compared with 1-h urine collections in the lactulose rhamnose (LR) dual sugar test. MethodsThree cohorts of undernourished children unresponsive to nutrition intervention underwent esophagogastroduodenoscopy and duodenal biopsies. Histopathology scores were compared to fecal calprotectin (CAL), myeloperoxidase (MPO), neopterin (NEO), and urinary LR ratio and lactulose percentage recovery. Log-transformed biomarkers were used in linear regressions adjusted for age, center, and sample collection–biopsy time interval in multivariable models. ResultsData on >1 biomarker were available for 120 Bangladeshi (CAL, MPO, NEO, and LR), 63 Pakistani (MPO, NEO, and LR), and 63 Zambian children (CAL). Median age at endoscopy was similar (19 mo) across centers. Median sample collection prior to endoscopy was consistent with each center’s study design: 2 wk in Bangladesh (urine and stool) and Zambia (stool), and 6 (urine) and 11 (stool) mo in Pakistan. In multivariable models, intraepithelial lymphocytes were associated with CAL (exponentiated [exp.] coefficient: 1.19; 95% confidence interval [CI]: 1, 1.41), intramucosal Brunner’s glands with MPO (exp. coefficient: 1.33; 95% CI: 1.05, 1.69) and NEO (exp. coefficient: 1.37; 95% CI: 1.1, 1.7), and chronic inflammation with NEO (exp. coefficient: 1.61; 95% CI: 1.17, 2.17). Intraepithelial lymphocytes were associated with lactulose % recovery (exp. coefficient: 1.22; 95% CI: 1.05, 1.41). LR recovery was substantially lower in 1-h collections than in 2-h collections. ConclusionsFour commonly used markers of enteric dysfunction were associated with specific histologic features. One-hour urine collection may be insufficient to reflect small bowel permeability in LR testing. While acknowledging the challenges with obtaining relevant tissue, these findings form the basis for further EED biomarker validation research.

Effect of Single High-Dose Vitamin D3 Supplementation on Post-Ultra Mountain Running Heart Damage and Iron Metabolism Changes: A Double-Blind Randomized Controlled Trial.

Exercise-induced inflammation can influence iron metabolism. Conversely, the effects of vitamin D3, which possesses anti-inflammatory properties, on ultramarathon-induced heart damage and changes in iron metabolism have not been investigated. Thirty-five healthy long-distance semi-amateur runners were divided into two groups: one group received 150,000 IU of vitamin D3 24 h prior to a race (n = 16), while the other group received a placebo (n = 19). Serum iron, hepcidin (HPC), ferritin (FER), erythroferrone (ERFE), erythropoietin (EPO), neopterin (NPT), and cardiac troponin T (cTnT) levels were assessed. A considerable effect of ultramarathon running on all examined biochemical markers was observed, with a significant rise in serum levels of ERFE, EPO, HPC, NPT, and cTnT detected immediately post-race, irrespective of the group factor. Vitamin D3 supplementation showed a notable interaction with the UM, specifically in EPO and cTnT, with no other additional changes in the other analysed markers. In addition to the correlation between baseline FER and post-run ERFE, HPC was modified by vitamin D. The ultramarathon significantly influenced the EPO/ERFE/HPC axis; however, a single substantial dose of vitamin D3 had an effect only on EPO, which was associated with the lower heart damage marker cTnT after the run.

Comparative Study of Blood Neopterin and Biopterins in Patients with COVID-19 and Secondary Bacterial Infection.

Background/Objectives: As COVID-19 can be severe, early predictive markers of both severity and onset of secondary bacterial infections are needed. This study first examined changes over time in the levels of plasma neopterin (NP) and biopterins (BPs), among others, in patients with COVID-19 and then in those with secondary bacterial infection complications. Methods: Fifty-two patients with COVID-19 admitted to two tertiary care centers were included. They were divided into a severe group (intubated + mechanical ventilation) (n = 10) and a moderate group (non-intubated + oxygen administration) (n = 42), and changes over time in plasma NP, plasma BPs, IFN-γ, lymphocyte count, CRP, and IL-6 were investigated. Four of the patients in the severe group (n = 10) developed secondary bacterial infections during treatment. Plasma NP and plasma BPs of patients with bacterial sepsis (no viral infection) (n = 25) were also examined. Results: The plasma NP, IL-6, CRP, and SOFA levels were significantly higher in the severe group, while the IFN-γ level and lymphocyte count were significantly lower. The higher plasma NP in the severe group persisted only up to 1 week after symptom onset. The plasma BPs were higher in complications of bacterial infection. Conclusions: The timing of sample collection is important for assessing severity through plasma NP, while plasma BPs may be a useful diagnostic tool for identifying the development of secondary bacterial infection in patients with COVID-19. Further investigation is needed to clarify the mechanism by which NP and BPs, which are involved in the same biosynthetic pathway, are differentially activated depending on the type of pathogen.

Neopterin, 7,8-dihydroneopterin, total neopterin levels and their ratio in periodontitis: New dilemma.

Determine the saliva and serum levels of neopterin (NP) and 7,8-dihydroneopterin (7,8NP) in periodontitis patients and to reveal the relationship of these data with clinical periodontal parameters. Twenty-three patients with stage III/grade B periodontitis and 23 periodontally healthy individuals were included. Clinical periodontal measurements were recorded (plaque index, pocket depth, clinical attachment loss & bleeding on probing). Saliva and serum levels of NP and 7,8NP were analyzed by high-performance liquid chromatography. Saliva NP, 7,8NP and Total Neopterin (TNP) levels were significantly elevated in the periodontitis than the control group (p < 0.001).ROC analyses of saliva NP, 7,8NP and TNP yielded areas under the curves of 0.873-0.938 for discriminating periodontitis from health, and saliva TNP was found the most accurate biomarker (AUC = 0.938).There was no significant difference among the periodontitis and control groups for saliva TNP/NP and TNP/7,8NP ratios and serum NP, 7,8NP and TNP levels (p > 0.05). Increased saliva TNP, NP and 7,8NP levels in periodontitis may suggest these biomarkers are regulating immune activation and oxidative stress mechanism in periodontal inflammation. Additionally, together with these results, equivalence of the TNP/NP ratio in intergroups may suggest that the effects of immune activation and oxidative stress mechanisms are equal in the periodontitis.

Neopterin in patients with COPD, asthma, and ACO: association with endothelial and lung functions

Background and objectiveEndothelial dysfunction has been widely recognized in chronic airway diseases, including chronic obstructive pulmonary disease (COPD) and asthma; however, it remains unclear in asthma-COPD overlap (ACO). Neopterin (NP), a metabolite of guanosine triphosphate, is a novel biomarker for identifying the increased risk of adverse cardiovascular events. This study aims to investigate the association of NP with endothelial dysfunction and impaired lung function in COPD, asthma, and ACO patients.MethodsA total of 77 subjects were prospectively recruited. All the participants underwent lung function test, endothelial function evaluation, including pulse wave velocity (PWV) and flow-mediated dilation (FMD), and blood sample detection. Moreover, the effect of NP on endothelial cells (ECs) in anoxic environments was assessed in vitro.ResultsEndothelial function was significantly decreased in the COPD and ACO patients compared with that in the healthy controls (P < 0.05). Forced expiratory volume in 1 s (FEV1) was negatively correlated with PWV and positively correlated with FMD (P < 0.05). NP was significantly increased in patients with chronic respiratory diseases compared with that in the control group, with COPD being the highest, followed by asthma, and ACO as the last (P < 0.05). The plasma level of NP exhibited negative correlations with FEV1 and positive correlations with PWV (P < 0.05). In vitro, a high level of NP increased the reactive oxygen species (ROS) and decreased the mitochondrial membrane potential (ΔΨm) of ECs dose-dependently in a hypoxic environment (P < 0.05).ConclusionNP was related to disease severity of chronic airway diseases and involved in the pathogenesis of endothelial dysfunction. A high NP level may contribute to endothelial dysfunction by increasing the oxidative stress of ECs dose-dependently in a hypoxic environment. Our findings may provide a novel evaluation and therapeutic target for endothelial dysfunction related to chronic airway diseases.

Exploring oxidative stress, immunological and metabolic biomarkers in dairy cows with postpartum pyometra.

Pyometra is a prevalent and severe infectious disease that affects the reproductive systems of cattle worldwide. This study's main goal was to investigate the biomarkers for oxidative stress (OS), adiponectin, leptin and neopterin (NPT) in cows suffering from postpartum pyometra. The study also aimed to determine which bacteria were most commonly implicated in the development of the disease. A total of 74 cows with pyometra were examined and compared to a control group of healthy cows (n = 20). In comparison to the healthy control and post-treatment groups, the pyometra group showed higher mean values of leptin, adiponectin and malondialdehyde (MDA). In contrast, the glutathione (GSH) and superoxide dismutase (SOD) mean values were lower in the pyometra group as compared to the post-treatment and control groups. NPT levels in the post-treatment groups were lower than those in cows with pyometra but comparable to the healthy control group (p > .05). When compared to the other biomarkers, NPT, leptin and adiponectin showed higher sensitivity and specificity in identifying pyometra cases (AUC ≥0.99). The predominant bacterial isolates from the ptomtra-affected cows consisted of Escherichia coli (N = 29; 39.2%), Arcanobacterium pyogenes (N = 27; 36.5%) and Fusobacterium necrophorum (N = 13; 17.6%). Mixed infection was determined in nine samples (12.2%). Conclusively, OS, adiponectin, leptin and NPT play crucial roles in comprehending the development of postpartum pyometra in cows and have the potential to serve as biomarkers for the disease.

Altered neopterin and IDO in kynurenine metabolism based on LC-MS/MS metabolomics study: Novel therapeutic checkpoints for type 2 diabetes mellitus

BackgroundThis study assessed the alternations of kynurenine pathway (KP) and neopterin in type 2 diabetes mellitus (T2DM) and explored possible differential metabolites. MethodsA fresh residual sera panel was collected from 80 healthy control (HC) individuals and 72 T2DM patients. Metabolites/ratios of interest including tryptophan (TRP), kynurenine (KYN), 5-hydroxytryptamine (5HT), kynurenic acid (KA), xanthurenic acid (XA), neopterin (NEO), KA/KYN ratio and KYN/TRP ratio were determined using a targeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) metabolomics approach, and the difference between groups was assessed. Supervised orthogonal partial least squares-discriminant analysis and differential metabolite screening with fold change (FC) were performed to identify distinct biomarkers. The diagnostic performance of KP metabolites in T2DM was evaluated. ResultsSignificant decreases of TRP, 5HT, KA, XA, and KA/KYN and increases of KYN/TRP and NEO in T2DM compared to HC group were observed (P < 0.05). The KP metabolites panel significantly changed between T2DM and HC groups (Q2: 0.925, P < 0.005). 5HT (FC: 0.63, P < 0.01) and NEO (FC: 3.27, P < 0.01) were proven to be distinct differential metabolites. A combined testing of fasting plasma glucose and KYN/TRP showed good value in the prediction of T2DM (AUC: 0.904, 95% CI 0.843–0.947). ConclusionsThe targeted LC-MS/MS metabolomics study is a powerful tool for evaluating the status of T2DM. This study facilitated the application of KP metabolomics into future clinical practice. 5HT and NEO are promising biomarkers in T2DM. KYN/TRP was highly associated with the development of T2DM and may serve as a potential treatment target.

Effect of a Homestead Food Production and Food Hygiene Intervention on Biomarkers of Environmental Enteric Dysfunction in Children Younger Than 24 Months in Rural Bangladesh: A Cluster-Randomized Controlled Trial.

Poor sanitation and hygiene practices and inadequate diets can contribute to environmental enteric dysfunction (EED). We evaluated the impact of a combined homestead food production and food hygiene intervention on EED biomarkers in young children in rural Bangladesh. The analysis was conducted within the Food and Agricultural Approaches to Reducing Malnutrition (FAARM) cluster-randomized trial in Sylhet, Bangladesh. The FAARM trial enrolled 2,705 married women and their children younger than 3 years of age in 96 settlements (geographic clusters): 48 intervention and 48 control. The 3-year intervention (2015-2018) included training on gardening, poultry rearing, and improved nutrition practices and was supplemented by an 8-month food hygiene behavior change component, implemented from mid-2017. We analyzed data on 574 children age 0 to 24 months with multilevel linear regression. We assessed fecal myeloperoxidase (MPO), neopterin (NEO), and alpha-1-antitrypsin (AAT) as biomarkers of EED, and serum C-reactive protein (CRP) and alpha-1-acid glycoprotein (AGP) as biomarkers of systemic inflammation, using ELISA. There was no intervention effect on NEO, AAT, CRP, and AGP concentrations, but, surprisingly, MPO levels were increased in children of the intervention group (0.11 log ng/mL; 95% CI, 0.001-0.22). This increase was greater with increasing child age and among intervention households with poultry that were not kept in a shed. A combined homestead food production and food hygiene intervention did not decrease EED in children in our study setting. Small-scale poultry rearing promoted by the intervention might be a risk factor for EED.

Graves hastalığında serum neopterin düzeylerinin değerlendirilmesi

Aim: Graves' disease is a disease with an autoimmune basis in which the synthesis and release of thyroid hormone from the thyroid gland increases. Interferon-gamma (IFN-γ) released from activated T lymphocytes causes macrophages to produce neopterin (NPT), increasing its concentration in serum and other body fluids. There is a relationship between NPT and the production of free oxygen radicals by these cells. In this study, it was aimed to measure serum NPT levels in individuals with Graves' disease.&#x0D; Material and Method: The study included 13 newly diagnosed Graves' patients (neopterin levels were measured at the time of first diagnosis and at the 3rd month of treatment) and 16 Graves' patients who were followed up in endocrinology outpatient clinics for at least one year. NPT levels of 23 healthy individuals without any disease were taken as the control group. Free triiodothyronine (T3), free thyroxine (T4), thyroglobulin, and thyroid stimulating hormone (TSH) levels were measured in the blood samples of the participants.&#x0D; Results: Serum NPT levels were found to be higher in Graves' patients compared to the control group (6.66 nmol/L in newly diagnosed patients, 9.24 nmol/L in patients at the 3rd month of treatment, 10.68 nmol/L in patients followed for one year or more, 1.44 nmol/L in the control group, respectively, p

Neopterin as a Potential Biomarker for the Early Diagnosis of Heart Failure: A Systematic Review and Meta-analysis.

Neopterin (NEO) is an inflammatory biomarker with proposed diagnostic value in cardiovascular diseases. Some correlations have been discovered between NEO levels and the incidence, severity, and adverse outcomes of heart failure (HF). However, there are discrepancies in the results reported in the literature. We conducted a systematic review and meta-analysis of studies comparing urinary and blood NEO concentrations between individuals with HF, cardiac insufficiency, or dilated cardiomyopathy (DCM) with control groups or those monitoring the role of NEO concentrations as a predictive marker of adverse outcomes in HF patients. A total of 24 studies that met the inclusion criteria were reviewed. The studies demonstrated the alteration of NEO in blood or urine samples in subjects with HF, cardiac insufficiency, or DCM compared with control groups. Also, reviewing the studies suggested a link between reduced ejection fraction, higher NYHA classes, and a higher risk of adverse cardiac outcomes with increased NEO levels. The meta-analysis of three studies revealed a significant increase in serum NEO levels in HF cases compared to that in healthy controls with an effect size of 3.72 (95 % CI 0.16 to 7.28; p = 0.04). Meta-analysis demonstrated a significant difference between serum NEO levels of HF cases and healthy subjects. This evidence implies the potential of serum NEO as a valuable diagnostic biomarker in HF patients. Also, the review of the studies revealed the prognostic potential of NEO. Further research is required to assess the usefulness of NEO as a diagnostic/prognostic biomarker for HF.

Urinary neopterin and biopterin indicate that inflammation has a role in autism spectrum disorder.

Inflammation is thought to be involved in the pathogenesis of autism spectrum disorder (ASD). Pteridine metabolites are biomarkers of inflammation that increase on immune system activation. In this study, we investigated the urinary pteridine metabolites in ASD patients as a possible biomarker for immune activation and inflammation. This observational, cross-sectional, prospective study collected urine samples from 212 patients with ASD and 68 age- and sex-matched healthy individuals. Urine neopterin (NE) and biopterin (BIO) levels were measured. Patients who had chronic disorders, active infection at the time of sampling, or high C-reactive protein levels were excluded. The urine NE and BIO concentrations were determined by high-performance liquid chromatography. The ratios of both NE and BIO to creatinine (CRE) were used to standardise the measurements. The NE/CRE and NE/BIO levels were significantly higher in ASD patients than controls. Univariate and multivariate models revealed a significant increase in NE/CRE and NE/BIO in ASD patients. There was a significant relationship between the NE/BIO [average area under the curve (AUC) = 0.717; range: 0.637-0.797] and NE/CRE (average AUC = 0.756; range: 0.684-0.828) ratios, which distinguished individuals with ASD from controls. The elevated NE/CRE and NE/BIO ratios suggest that inflammation and T cell-mediated immunity are involved in the pathophysiology of autism. NE/BIO could serve as a diagnostic inflammatory marker in the pathogenesis of ASD.

Abnormal kynurenine-pathway metabolites in gout: Biomarkers exploration based on orthogonal partial least squares-discriminant analysis

BackgroundThis study aims to investigate serological characteristics of kynurenine pathway (KP) metabolites in healthy controls (HC) and gout patients and explore possible differential metabolites. MethodsA total of 191 individual fresh residual sera was collected from 129 HC and 62 gout patients. A liquid chromatography-tandem mass spectrometry method was fully validated to measure 6 metabolites, including tryptophan (TRP), kynurenine (KYN), 5-hydroxytryptamine (5HT), kynurenic acid (KA), xanthurenic acid (XA), and neopterin (NEO). Supervised orthogonal partial least squares-discriminant analysis (OPLS-DA) and differential metabolite screening with fold change (FC) were performed to identify intrinsic variations and differential levels of KP metabolites between the HC and gout groups. Logistic regression was used to assess the contributions of KP metabolites to gout. ResultsThere were significant decreases of TRP, 5HT, XA, and NEO and increases of KYN, KA, KA/KYN, and KYN/TRP in gout patients compared to the HC group (all p < 0.05). KP metabolites of the gout group showed good discrimination from those of the HC group (Q2: 0.892). Two distinct different metabolites were identified in gout, i.e., XA (FC: 0.56, p < 0.01) and NEO (FC: 0.34, p < 0.01). Of the KP metabolites, KYN was strongly associated with gout (OR: 7.91, p < 0.01). ConclusionsAbnormal levels of serum KP metabolites were observed in gout. XA and NEO are promising biomarkers that were relevant to the status of gout. The level of KYN could be an attractive checkpoint for the management of gout. Continuous monitoring of KP metabolism in gout provides new opportunities to predict therapeutic efficacy and prognosis.

The prognostic value of the NPT test combined with amplitude integrated electroencephalogram in children with VE and its bioreliability analysis.

Viral encephalitis (VE) is one of the common diseases of children with intracranial infection, it has come on urgent, progress is fast, and the clinical features of severe cases may even lead to disability, death, and other serious adverse prognostic outcomes, so seek in early diagnosis and prognosis of efficiency of the relevant indicators to stop in time and take effective means to prevent the further development is of great significance. Neopterin (NPT), as a factor that plays an important role in the process of validation development, has been relatively rarely studied in children with VE. In this study, 127 cases of children with VE were retrieved from the TCGA database by bioinformatics, and their amplitude integrated electroencephalogram (AEEG) related information was collected at the same time. The neurodevelopmental status of VE children was evaluated according to the Gesell scale and divided into the good group (n=88) and the poor group (n=39). The differences in NPT expression and AEEG score between them were observed. In addition, the clinical data of 100 children without VE were screened from the database, and the differences in NPT expression and AEEG score between VE children and non-VE children were compared. The ROC curve was used to evaluate the clinical efficacy of NPT combined with AEEG in diagnosis and prognosis prediction. Kaplan-Meier was used to observe the effect of NPT high expression and low expression on poor prognosis of VE children.

Faecal markers of intestinal inflammation in slum infants following yogurt intervention: A pilot randomized controlled trial in Bangladesh

IntroductionWe evaluated the effects of yogurt supplementation and nutrition education to low educated mothers on infant-gut health at an early age.MethodsWe designed a three-arm pilot randomized controlled trial with 162 infants aged 5-6 months and at risk of stunting (LAZ ≤-1 SD and &amp;gt;-2 SD at enrollment) living in slum areas in Dhaka, Bangladesh. Eligible children were randomized to receive, 1) nutrition education, 2) yogurt supplementation plus nutrition education or 3) usual care. Three faecal inflammatory biomarkers alpha-1 antitrypsin (AAT), myeloperoxidase (MPO), and neopterin (NEO) were measured before and after three months of yogurt feeding. ResultsAt the end of three months, there were no significant differences in the biomarker concentrations between the yogurt plus group and control. Compared to control, the adjusted mean faecal NEO concentration decreased by 21% (NEO: RR 0.79, 95% CI: 0.60, 1.04) and the adjusted mean faecal AAT concentration decreased by 8% (AAT: RR 0.92, 95% CI: 0.69, 1.22); whereas, the adjusted mean faecal MPO concentration increased by 14% (MPO: RR 1.14, 95% CI: 0.62, 2.09). Such changes were not apparent in the education only group. DiscussionAfter a three-month trial of daily yogurt feeding to children at risk of stunting and infant feeding education to their mothers, reduction in one inflammatory biomarker reached close to statistical significance, but not all of the measured biomarkers. The study did not finish its endline measurements at 6-month as designed due to COVID 19 pandemic. This has greatly impacted the interpretation of the results as we could not establish a decreasing trend in biomarker concentration with continued yogurt feeding.

The efficacy of haemoperfusion combined with continuous venovenous haemodiafiltration in the treatment of severe viral encephalitis in children

BackgroundThis study investigated the efficacy of the integrated blood purification mode of early haemoperfusion (HP) combined with continuous venovenous haemodiafiltration (CVVHDF) in children with severe viral encephalitis, and evaluated the correlation of cerebrospinal fluid (CSF) neopterin (NPT) levels with prognosis.MethodsThe records of children with viral encephalitis who received blood purification treatment in the authors’ hospital from September 2019 to February 2022 were retrospectively analysed. According to the blood purification treatment mode, they were divided into the experimental group (HP + CVVHDF, 18 cases), control group A (CVVHDF only, 14 cases), and control group B (16 children with mild viral encephalitis who did not receive blood purification treatment). The correlation between the clinical features, severity of the disease and the extent of lesions on brain magnetic resonance imaging (MRI) and the CSF NPT levels was analysed.ResultsThe experimental group and control group A were comparable with respect to age, gender and hospital course (P > 0.05). There was no significant difference in speech and swallowing functions between the two groups after treatment (P > 0.05) and no significant difference in 7 and 14-day mortality (P > 0.05). The CSF NPT levels in the experimental group before treatment were significantly higher compared with control group B (P < 0.05). The extent of brain MRI lesions correlated positively with CSF NPT levels (P < 0.05). In the experimental group (14 cases), the serum NPT levels decreased after treatment, whereas the CSF NPT levels increased after treatment, and the differences were statistically significant (P < 0.05). Dysphagia and motor dysfunction correlated positively with CSF NPT levels (P < 0.05).ConclusionEarly HP combined with CVVHDF in the treatment of severe viral encephalitis in children may be a better approach than CVVHDF only for improving prognosis. Higher CSF NPT levels indicated the likelihood of a more severe brain injury and a greater possibility of residual neurological dysfunction.

Adequacy of Iodine Status and Associations with Gut Health: A Prospective Cohort Study among Infants in 8 Low- and Middle-Income Countries

BackgroundEnvironmental enteric dysfunction increases the likelihood of micronutrient deficiencies among infants, but few studies have assessed the potential impact of gut health on urinary iodine concentration (UIC) among this vulnerable group. ObjectivesWe describe the trends of iodine status among infants from 6 to 24 mo old and examine the associations between intestinal permeability, inflammation, and UIC from 6 to 15 mo of age. MethodsData from 1557 children enrolled in this birth cohort study conducted in 8 sites were included in these analyses. UIC was measured at 6, 15, and 24 mo of age by using the Sandell-Kolthoff technique. Gut inflammation and permeability were assessed using the concentrations of fecal neopterin (NEO), myeloperoxidase (MPO) and alpha-1–antitrypsin (AAT), and lactulose–mannitol ratio (LM). A multinomial regression analysis was used to assess the classified UIC (deficiency or excess). Linear mixed regression was used to test the effect of interactions among biomarkers on logUIC. ResultsAll studied populations had adequate (≥100 μg/L) to excess (≥371 μg/L) median UIC at 6 mo. Between 6 and 24 mo, 5 sites displayed a significant decline in the infant’s median UIC. However, median UIC remained within the optimal range. An increase of NEO and MPO concentrations by +1 unit in ln scale reduced the risk of low UIC by 0.87 (95% CI: 0.78–0.97) and 0.86 (95% CI: 0.77–0.95), respectively. AAT moderated the association between NEO and UIC (P < 0.0001). The shape of this association appears to be asymmetric and in a reverse J-shape, with a higher UIC observed at both lower NEO and AAT concentrations. ConclusionsExcess UIC was frequent at 6 mo and tended to normalize at 24 mo. Aspects of gut inflammation and increased permeability appear to reduce the prevalence of low UIC in children aged 6 to 15 mo. Programs addressing iodine-related health should consider the role of gut permeability in vulnerable individuals.

Impact of enteropathogens on faltering growth in a resource-limited setting.

Environmental enteropathy is an important contributor to childhood malnutrition in the developing world. Chronic exposure to fecal pathogens leads to alteration in intestinal structure and function, resulting in impaired gut immune function, malabsorption, and growth faltering leading to environmental enteropathy. A community-based intervention study was carried out on children till 24 months of age in Matiari district, Pakistan. Blood and fecal specimens were collected from the enrolled children aged 3-6 and 9 months. A real-time PCR-based TaqMan array card (TAC) was used to detect enteropathogens. Giardia, Campylobacter spp., enteroaggregative Escherichia coli (EAEC), Enteropathogenic Escherichia coli (EPEC), Enterotoxigenic Escherichia coli (ETEC), and Cryptosporidium spp. were the most prevailing enteropathogens in terms of overall positivity at both time points. Detection of protozoa at enrollment and 9 months was negatively correlated with rate of change in height-for-age Z (ΔHAZ) scores during the first and second years of life. A positive association was found between Giardia, fecal lipocalin (LCN), and alpha 1-Acid Glycoprotein (AGP), while Campylobacter spp. showed positive associations with neopterin (NEO) and myeloperoxidase (MPO). Protozoal colonization is associated with a decline in linear growth velocity during the first 2 years of life in children living in Environmental enteric dysfunction (EED) endemic settings. Mechanistic studies exploring the role of cumulative microbial colonization, their adaptations to undernutrition, and their influence on gut homeostasis are required to understand symptomatic enteropathogen-induced growth faltering.

Dynamika klinichnykh oznak i pokaznykiv biomarkera zapalennia neopterynu v syrovattsi krovy krolykiv iz eksperymentalnym neinfektsiinym avtoimunnym uveitom, z urakhuvanniam riznoho stupenia tiazhkosty

Introduction. Uveitis is an inflammatory condition involving iris, ciliary body and choroid of the eyebulb. Uveitis curretntly affects about two million people worldwide and is among five leading causes of blindness in the working population. Diagnosis of uveitis requires a number of investigations. As important biomarker in the diagnosis of uveitis can be used the detection of Neopterin (NP) in blood serum, since it is a stable metabolite and its increased level encompass activation of cellular immunity. It should be also noted that NP is present in blood serum and plasma, urine, tears, aqueous humor, vitreous body, other biological fluids and can be easily detected. According to literature data and our own investigations, the concentration of NP usually depends on the degree of activity of the pathological process, and its high concentration of NP is one of the main predictors of an unfavorable prognosis. The aim of the study. To investigate the dynamics of clinical signs and inflammatory biomarker Neopterin level in blood serum of rabbits with experimental non-infectious autoimmune uveitis (NAU) considering varying degrees of severity. Materials and methods. The experimental study was conducted on 30 rabbits of the “Chinchilla” breed, which were divided into two main groups (I and II), 15 animals in each. NAU was induced by intravitreal injection of an undiluted normal sterile horse serum to group I rabbits, while group II animals received diluted with the physiological solution serum in the proportion of 1:2. General sensitization was previously carried out with the same serum injected intravenously. Results. The average level of NP in rabbits before the start of the experiment was 1.7 ± 0.2 nmol/l. It was considered the norm, since there is no information in the literature about the study of NP in healthy rabbits of the “Chinchilla” breed. In the reported research the severity of experimental NAU was estimated due to the concentration of the injected normal sterile horse serum intravitreally. As an additional proof of the development of NAU clinical picture was used the detection of Neopterin concentration in blood serum of rabbits. In both group animals the development of acute inflammation on days 3, 7, 10 and 14 of experiment the NP level was significantly higher compared to control (p-value less than 0.05). However, in the I group animals with moderate and severe NAU, the level of NP was significantly higher than that in group II, in which uveitis was characterized by a mild course. Namely, on the 3rd day of experiment NP concentration in the I group animals was 5.60 ± 0.70 nmol/l, in the group II – 4.70 ± 0.60 nmol/l (p-value less than 0.05); on day 7th – 6.00 ± 0.20 nmol/l and 4.45 ± 0.30 nmol/l (p-value less than 0.05); on day 10th – 5.90 ± 0.40 nmol/l and 2.60 ± 0.40 nmol/l (p-value less than 0.05); on the 14th – 3.80 ± 0.40 nmol/l and 2.10 ± 0.10 nmol/l (p-value less than 0.05). On the day 21st, the NP concentration in both group animals did not differ statistically – estimated level 2.70 ± 0,30 nmol/l, (p-value more than 0.05) – which apparently encompass the regression of inflammatory changes in the eye. Conclusions. A correlation between the severity of experimental non-infectious autoimmune uveitis with concentration of inflammatory biomarker neopterin in blood serum was investigated in rabbits. NP level in all experimental animals was elevated and statistically different in comparison to NP control levels on days 3rd, 7th, 10th and 14th day of experiment. In the group of animals with a more severe course of uveitis, a significantly higher level of NP was noted compared to animals with a milder course of NAU. This observation confirms the immune response to inflammation and the stability of NP biomarker in blood serum. The dynamics of this biomarker levels in rabbits of two experimental groups has a correlation with the dynamics of clinical changes. Detection of the inflammatory biomarker Neopterinin in blood serum can be used as a criterion for assessement the severity of non-infectious autoimmune uveitis, its course and, probably, prognosis.

COVID-19 Mimics Pulmonary Dysfunction in Muscular Dystrophy as a Post-Acute Syndrome in Patients

Although progressive wasting and weakness of respiratory muscles are the prominent hallmarks of Duchenne muscular dystrophy (DMD) and long-COVID (also referred as the post-acute sequelae of COVID-19 syndrome); however, the underlying mechanism(s) leading to respiratory failure in both conditions remain unclear. We put together the latest relevant literature to further understand the plausible mechanism(s) behind diaphragm malfunctioning in COVID-19 and DMD conditions. Previously, we have shown the role of matrix metalloproteinase-9 (MMP9) in skeletal muscle fibrosis via a substantial increase in the levels of tumor necrosis factor-α (TNF-α) employing a DMD mouse model that was crossed-bred with MMP9-knockout (MMP9-KO or MMP9-/-) strain. Interestingly, recent observations from clinical studies show a robust increase in neopterin (NPT) levels during COVID-19 which is often observed in patients having DMD. What seems to be common in both (DMD and COVID-19) is the involvement of neopterin (NPT). We know that NPT is generated by activated white blood cells (WBCs) especially the M1 macrophages in response to inducible nitric oxide synthase (iNOS), tetrahydrobiopterin (BH4), and tetrahydrofolate (FH4) pathways, i.e., folate one-carbon metabolism (FOCM) in conjunction with epigenetics underpinning as an immune surveillance protection. Studies from our laboratory, and others researching DMD and the genetically engineered humanized (hACE2) mice that were administered with the spike protein (SP) of SARS-CoV-2 revealed an increase in the levels of NPT, TNF-α, HDAC, IL-1β, CD147, and MMP9 in the lung tissue of the animals that were subsequently accompanied by fibrosis of the diaphragm depicting a decreased oscillation phenotype. Therefore, it is of interest to understand how regulatory processes such as epigenetics involvement affect DNMT, HDAC, MTHFS, and iNOS that help generate NPT in the long-COVID patients.

Zinc Sulfate and Omega-3: Do They Have a Role in Environmental Enteric Dysfunction ?

Introduction: Environmental enteric dysfunction (EED) is a subclinical, chronic inflammatory condition of the gut. The purpose of the study: The purpose of this study is to evaluate the effects of zinc sulphate and omega-3 supplementation on anthropometric measurements and faecal EED biomarkers (α-1-antitrypsin (AAT), Neopterin (NEO), and Myeloperoxidase (MPO) in underweight and stunted children as an intervention for EED. Subjects and Methods: An interventional study included 105 underweight and stunted children, divided into two subgroups: one subjected to intervention with zinc supplementation (55 children) and the other subjected to intervention with omega-3 supplementation (50 children) for 6 months. Assessment of anthropometric measurements and faecal EED biomarkers: AAT, NEO, and MPO. Results: Regarding the zinc intervention group, post-intervention weight, weight z score, height, height z score, and BMI z score were highly significantly improved after 6 months of zinc supplementation (p value ≤ 0.001). Serum zinc level was highly significant increased after supplementation (p value ≤ 0.001), while AAT and NEO were highly significant and significant decreased (p value ≤ 0.001) (p value ≤ 0.05) respectively. Regarding the omega-3 intervention group, post-intervention weight, weight z score, height, and height z score were highly significantly improved after 6 months of omega-3 supplementation (p value ≤ 0.001). Meanwhile, no significant change was observed for serum iron and zinc level (p value ≥ 0.05) or EED faecal markers except for AAT, which was highly significant for decreasing after supplementation (p value ≤ 0.001). A significant increase in weight, height, and serum zinc level was observed in the zinc supplementation group more than in the omega-3 supplementation group (p value ≤ 0.05). Alongside no significant difference post intervention in EED fecal markers between the two groups (p value ≥ 0.05). Conclusion: No definite drug intervention or supplementation is documented as appropriate management. Zinc sulphate supplementation is thought to be more beneficial than omega-3 supplementation, as evidenced by the improvement of anthropometric measurements and decrease of EED faecal markers.