Blood Levels Of Protein Research Articles

Hippocratea africana Root Extract and Fractions Ameliorates Paracetamol (PCM)-Induced Oxidative Stress and Liver Injuries in Rats

Aim: The antidotal potential of Hippocratea africana root, which is used locally to cure poisoning, was studied in rats.
 Methodology: The hepatoprotective activity of the root extract (200-600 mg/kg), fractions (dichloromethane (DCM) and aqueous, 400 mg/kg) and Silymarin (100 mg/kg), were investigated against paracetamol-induced liver injury in rats. Assay of liver function parameters, markers of antioxidative stress in addition to liver histological analysis were employed to evaluate the hepatoprotective potential of root extract and fractions.
 Results: Administration of the root extract (200-600 mg/kg) caused significant (P < .05-.001) increases in the blood levels of total protein and decreases in direct and total bilirubin, and the liver biomarker enzymes ALT, AST, and ALP caused by paracetamol administration. Most of the time, the effects were dose-dependent. When compared to the negative control group of animals (organotoxic-treated animals), the histology of the liver sections from animals treated with extract, fractions, and silymarin revealed a decrease in pathological characteristics. These histological observations suggest significant hepatoprotective potentials which were in line with the chemical pathological alterations.
 Conclusion: The outcome of the study indicated that root extract and fractions of Hippocratea africana have antioxidative stress potentials and hepatoprotective action against harmful substances, maybe as a result of its phytochemical constituents' activity.

Leptospirosis-associated meningitis in a patient with sjögren’s syndrome: a case report

BackgroundLeptospirosis is a zoonotic disease that afflicts both humans and animals. It progresses from flu-like symptoms to more severe hepatic and renal failure, and may also lead to aseptic meningitis. Individuals with autoimmune diseases (ADs) are potentially more susceptible to Leptospirosis. Thus far, limited data has documented the association between Leptospirosis and autoimmune disorders.Case presentationThe patient had a definitive pathological diagnosis of Sjögren’s syndrome (SS). Due to recurrent headaches, the patient sought consultation with a neurologist. Lumbar puncture revealed elevated white blood cells and protein levels in the cerebrospinal fluid, along with decreased glucose. Tuberculous meningitis was suspected. Radiographic imaging exhibited meningeal enhancement, ventricular enlargement, and hydrocephalus. The patient commenced treatment with anti-tuberculosis therapy and corticosteroids. Subsequently, high-throughput sequencing (HTS) of cerebrospinal fluid identified the presence of Leptospira interrogans. The patient was ultimately diagnosed with Leptospiral meningitis, and underwent antimicrobial and immunosuppressive therapy, resulting in stabilization of the condition and gradual symptom recovery.ConclusionsThe case highlights the challenges in diagnosing and managing leptospirosis-related meningitis in the presence of ADs and emphasizes the importance of utilizing HTS for accurate pathogen detection. The potential correlation between leptospirosis and SS warrants further investigation, as does the need for multidisciplinary involvement in treatment strategies for such complex cases.

Some neurological and laboratory indexes in active duodenal ulcer depending on Helicobacter pylori presence

Somatic-neurological and psychosomatic relationships are an integral part of the pathophysiological mechanisms in numerous diseases. The results of one of the fragments of a comprehensive clinical and paraclinical study of the nervous system state indexes in active duodenal ulcer (DU) are reported. It aimed to assess the effect of Helicobacter pylori (H.pylori) on clinical-neurological and laboratory indexes. Sixty persons with an average age of 39.80 ± 1.29 years were examined. The patients were divided into two groups based on H.pylori presence or absence. The examinations included the following: analysis of complaints according to the developed questionnaire, neurological status assessment, autonomic dysfunction analysis (by A.M. Vayn questionnaire), complete blood count, evaluating the levels of C-reactive protein, total cholesterol, urea and creatinine in blood, neutrophil-to-lymphocyte and platelet-to-lymphocyte ratio calculation. The appropriate statistical methods were used for data processing. It was found that complaints of headache, dizziness and paresthesia as well as asthenodepressive syndrome and polyneuropathy of various severity and with different clinical manifestations were more common (p < 0.05) in patients with active DU on the background of Н.pylori. Sympathicotonia was significantly more frequent and eutonia was significantly less frequent in the active DU in patients infected with Н.pylori. An increased C-reactive protein level was significantly more common in Н.pylori patients. The identified neurological and laboratory features indicate a probable pathophysiological significance of Н.pylori in somatoneurological relationships, particularly in DU.

The occurrence and development of vertebral osteoporosis regulated by IL-8.

Vertebral osteoporotic fracture is a common type of fracture, and the incidence is higher in the elderly. However, the relationship between vertebral osteoporotic fractures and interleukin-8 (IL-8) remains unclear. A total of 163 patients with osteoporotic vertebral fractures were recruited. Clinical and follow-up data were recorded, and the expression levels of IL1, MMP9, IL-8, and C-reactive protein in blood were measured. Pearson Chi-square test and Spearman correlation coefficient were used to analyze the relationship between vertebral osteoporotic fractures and related parameters. Univariate and multivariate logistic regression and univariate and multivariate Cox proportional hazards regression were used for further analysis. Pearson chi-square test, Spearman correlation coefficient and Logistic regression analysis showed that IL1 and IL-8 were significantly associated with vertebral osteoporotic fractures. Univariate Cox regression analysis showed that age and IL-8 expression level were significantly associated with maintenance time from recovery to recurrence of vertebral osteoporotic fractures. Multivariate Cox regression analysis showed that IL-8 expression level was significantly associated with maintenance time from recovery to recurrence of vertebral osteoporotic fractures. The higher the expression level of IL-8, the more likely it is to develop vertebral osteoporotic fracture, and the more likely it is to relapse in a short time.

First Results from a Phase 1, First-in-Human Study of the Bruton's Tyrosine Kinase (BTK) Degrader Bgb-16673 in Patients (Pts) with Relapsed or Refractory (R/R) B-Cell Malignancies (BGB-16673-101)

Introduction: BTK inhibitors (BTKis) are approved for chronic lymphocytic leukemia (CLL), Waldenström macroglobulinemia (WM), mantle cell lymphoma (MCL), and marginal zone lymphoma (MZL). Disease that progresses on BTKis often has BTK mutations that lead to treatment (tx) resistance; novel BTK-targeting agents that overcome BTKi resistance are needed. BGB-16673 is a heterobifunctional small molecule that binds to BTK and E3 ligase, resulting in BTK degradation via ubiquitination. In preclinical models, BGB-16673 degraded wild-type (WT) BTK and known covalent and noncovalent BTKi-resistant mutant proteins, leading to tumor suppression. Methods: Pts with R/R CLL, WM, MCL, MZL, non-germinal center B-cell diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), or Richter transformation (RT) were eligible for this open-label, first-in-human, phase 1 trial (BGB-16673-101; NCT05006716). Pts must have received ≥2 prior therapies (≥1 for RT) and have an ECOG performance status of 0-2 and adequate end-organ function. In the US and Australia, pts must have received a covalent BTKi (cBTKi) if approved for their disease. BGB-16673 was dosed daily by mouth in 28-day cycles. Escalation using a Bayesian optimal interval design with 6 dose levels (50-600 mg once daily) is planned. Primary objectives are to assess safety/tolerability and establish the maximum tolerated dose (MTD) and recommended phase 2 dose. Key secondary objectives are to assess pharmacokinetics, pharmacodynamics (PD), and preliminary antitumor activity. Safety was assessed according to CTCAE v5.0 (all pts) and iwCLL hematologic toxicity criteria (pts with CLL). Dose-limiting toxicities (DLTs) were assessed in the first 4 weeks. Response was assessed per Lugano criteria for all except CLL (iwCLL 2018 criteria) and WM (iwWM-6 criteria). Results: As of May 26, 2023, 26 pts (10 CLL, 4 MCL, 2 MZL, 4 WM, 4 FL, 1 DLBCL, 1 RT) were enrolled at 5 dose levels (50 mg, 4; 100 mg, 9; 200 mg, 9; 350 mg, 3; 500 mg, 1). Median age was 70.5 y (range, 25-83). Median number of prior therapies was 3.5 (range, 2-9), including cBTKis (n=21; 10 CLL, 4 WM, 4 MCL, 1 MZL, 1 RT, 1 DLBCL), BCL2 inhibitors (n=12; 9 CLL, 2 WM, 1 RT), and noncovalent BTKis (ncBTKis; n=4; 2 CLL, 1 WM, 1 FL). In CLL, del17p/ TP53 mutation (n=8) and unmutated IGHV (n=7) were frequent. Median follow-up was 3.5 mo (range, 0.2-13.9). MTD was not reached. Treatment-emergent AEs (TEAEs) were reported by 88.5% of pts (grade [gr] ≥3, 46.2%; serious, 38.5%). The most common TEAEs were contusion (30.8%; no gr ≥3), pyrexia (23.1%; no gr ≥3), neutropenia/neutrophil count decreased (23.1%; gr ≥3, 15.4%), and lipase increased (23.1%; gr ≥3, 3.8%; all transient and asymptomatic). No hypertension or atrial fibrillation was observed. One pt died from sepsis with possible disease progression. No discontinuations due to AEs occurred. Two pts had dose reductions due to TEAEs (gr 3 hematuria with urinary tract infection and recurrent urothelial carcinoma and gr 2 arthralgia). One DLT occurred in 1 pt at 200 mg (gr 3 maculopapular rash on day 27; after 5-day dose hold, assigned dose was recommenced with persistent gr 1 rash). BGB-16673 exposure increased in a dose-dependent manner. At steady state with doses ≥50 mg daily, BGB-16673 exposure exceeded the calculated half maximal degradation concentration for WT and cysteine 481-mutated BTK for the dosing interval. Preliminary PD data showed deep, sustained reductions in BTK protein levels in peripheral blood and tumor tissue, even at the lowest dose. Most CLL pts experienced lymphocytosis during the first 3 cycles of tx. Twenty of 26 pts (77%) remain on therapy (discontinuation: 4 progressive disease, 2 withdrawal). Of 18 response-evaluable pts, 12 (67%) responded (5/6 CLL, 1/3 MCL, 2/2 MZL, 3/4 WM, 1/2 FL, 0/1 DLBCL; 1 CR in MCL, all others had PR; Figure), including pts who received a cBTKi (n=10) and an ncBTKi (n=2). Responses started at the lowest dose level. All responders remain in response, the longest responder remaining on tx for 60 weeks. Conclusions: Preliminary data from this ongoing, first-in-human study of the novel BTK degrader BGB-16673 demonstrate a tolerable safety profile and clinical responses in heavily pretreated pts with B-cell malignancies, including those with BTKi-resistant disease. Substantial reductions in BTK protein levels in peripheral blood and tumor tissue were also observed, demonstrating proof-of-concept of a strong, on-target effect.

Protein Biomarkers and Major Cardiovascular Events in Older People With Advanced CKD: The European Quality (EQUAL) Study

Rationale & ObjectiveCardiovascular disease is the leading cause of morbidity and mortality in chronic kidney disease (CKD). We investigated 184 inflammatory and cardiovascular proteins to determine their potential as biomarkers for major cardiovascular events (MACE). Study DesignEQUAL is an observational cohort study which enrolled people aged ≥65 years with an estimated glomerular filtration rate ≤20 ml/min/1.73m2. Setting & ParticipantsRecruited participants were split into Discovery (n=611) and Replication cohorts (n=292). ExposureOne hundred and eighty four blood protein levels measured at the baseline visit, each protein was analysed individually. OutcomeMACE. Analytical ApproachCox proportional hazard models adjusted for age, sex, eGFR, previous MACE and country were used to determine the risk of MACE. Proteins with false discovery rate adjusted P values <0.05 in the Discovery cohort were tested in the Replication cohort. Sensitivity analyses were performed, adjusting for traditional risk factors, CKD-specific risk factors and level of proteinuria, and with atherosclerotic and non-atherosclerotic MACE segregated. ResultsDuring 2.9 years median follow-up, 349 people (39%) experienced a MACE. Forty-eight proteins were associated with MACE in the Discovery cohort; 9 of these were reproduced in the Replication cohort. Three of these proteins maintained a strong association with MACE after adjustment for traditional and CKD-specific risk factors, and proteinuria. Tenascin (TNC), fibroblast growth factor-23 (FGF-23) and V-set and Immunoglobulin Domain containing protein 2 (VSIG2) were associated with both atherosclerotic and non-atherosclerotic MACE. All replicated proteins except carbonic anhydrase 1 and carbonic anhydrase 3 were associated with non-atherosclerotic MACE. LimitationsSingle protein concentration measurements and limited follow up time. ConclusionsOur findings corroborate previously reported relationships between FGF-23, vascular cell adhesion protein-1, TNC and placental growth factor with cardiovascular outcomes in CKD. We identify 5 proteins not previously linked with MACE in CKD, that may be targets for future therapies.

Blood biomarkers of neuronal injury in paediatric cerebral malaria and severe malarial anaemia

Abstract Persistent neurodisability is a known complication in paediatric survivors of cerebral malaria and severe malarial anaemia. Tau, ubiquitin C-terminal hydrolase-L1, neurofilament-light chain, and glial fibrillary acidic protein have proven utility as biomarkers that predict adverse neurologic outcomes in adult and paediatric disorders. In paediatric severe malaria, elevated tau is associated with mortality and neurocognitive complications. We aimed to investigate whether a multi-analyte panel including ubiquitin C-terminal hydrolase-L1, neurofilament-light chain, and glial fibrillary acidic protein can serve as biomarkers of brain injury associated with mortality and neurodisability in cerebral malaria and severe malarial anaemia. In a prospective cohort study of Ugandan children, 18 months to 12 years of age with cerebral malaria (n = 182), severe malarial anaemia (n = 158), and asymptomatic community children (n = 118), we measured admission blood levels of ubiquitin C-terminal hydrolase-L1, neurofilament-light chain, and glial fibrillary acidic protein. We investigated differences in biomarker levels, associations with mortality, blood–brain barrier integrity, neurodeficits and cognitive Z-scores in survivors up to 24-month follow-up. Admission ubiquitin C-terminal hydrolase-L1 levels were elevated &amp;gt;95th percentile of community children in 71 and 51%, and neurofilament-light chain levels were elevated &amp;gt;95th percentile of community children in 40 and 37% of children with cerebral malaria and severe malarial anaemia, respectively. Glial fibrillary acidic protein was not elevated in disease groups compared with controls. In cerebral malaria, elevated neurofilament-light chain was observed in 16 children who died in hospital compared with 166 survivors (P = 0.01); elevations in ubiquitin C-terminal hydrolase-L1 levels were associated with degree of blood–brain barrier disruption (P = 0.01); and the % predictive value for neurodeficits over follow-up (discharge, 6-, 12-, and 24 months) increased for ubiquitin C-terminal hydrolase-L1 (60, 67, 72, and 83), but not neurofilament-light chain (65, 68, 60, and 67). In cerebral malaria, elevated ubiquitin C-terminal hydrolase-L1 was associated with worse memory scores in children &amp;lt;5 years at malaria episode who crossed to over 5 years old during follow-up cognitive testing [β −1.13 (95% confidence interval −2.05, −0.21), P = 0.02], and elevated neurofilament-light chain was associated with worse attention in children ≥5 years at malaria episode and cognitive testing [β −1.08 (95% confidence interval −2.05, −1.05), P = 0.03]. In severe malarial anaemia, elevated ubiquitin C-terminal hydrolase-L1 was associated with worse attention in children &amp;lt;5 years at malaria episode and cognitive testing [β −0.42 (95% confidence interval −0.76, −0.07), P = 0.02]. Ubiquitin C-terminal hydrolase-L1 and neurofilament-light chain levels are elevated in paediatric cerebral malaria and severe malarial anaemia. In cerebral malaria, elevated neurofilament-light chain is associated with mortality whereas elevated ubiquitin C-terminal hydrolase-L1 is associated with blood–brain barrier dysfunction and neurodeficits over follow-up. In cerebral malaria, both markers are associated with worse cognition, while in severe malarial anaemia, only ubiquitin C-terminal hydrolase-L1 is associated with worse cognition.

Evaluation of the Effect of Oral Isotretinoin on the Level of Serum YKL40 in Acne Vulgaris Patients: A Cross-Sectional Case-Control.

In the entire world, acne vulgaris (AV) is the most prevalent skin condition. Approximately 9.4% of people worldwide have acne vulgaris. This study compared the blood levels of chitinase 3-like protein 1 (YKL-40) in acne vulgaris patients before and after oral isotretinoin therapy. The design of the study was cross-sectional case-control. Forty patients with moderate to severe acne vulgaris and twenty healthy participants participated in this study. Using the Global Acne Grading System (GAGS) score, patients with acne vulgaris were evaluated both before and after concluding their treatment. Using the enzyme-linked immunosorbent assay (ELISA), the serum levels of YKL-40 were measured before and after oral isotretinoin therapy in healthy controls and acne patients. Patients with acne vulgaris had considerably greater serum levels of YKL-40 than healthy control subjects (p 0.001) did. After three months of oral isotretinoin medication, the GAGS score and blood levels of YKL-40 in acne vulgaris patients both significantly decreased. The conclusion of this study was that reducing the blood levels of YKL-40 and the GAGS score in patients with acne vulgaris who took oral isotretinoin for three months was a crucial strategy.

Inhibitors of the Elastase LasB for the Treatment of Pseudomonas aeruginosa Lung Infections.

Infections caused by the Gram-negative pathogen Pseudomonas aeruginosa are emerging worldwide as a major threat to human health. Conventional antibiotic monotherapy suffers from rapid resistance development, underlining urgent need for novel treatment concepts. Here, we report on a nontraditional approach to combat P. aeruginosa-derived infections by targeting its main virulence factor, the elastase LasB. We discovered a new chemical class of phosphonates with an outstanding in vitro ADMET and PK profile, auspicious activity both in vitro and in vivo. We established the mode of action through a cocrystal structure of our lead compound with LasB and in several in vitro and ex vivo models. The proof of concept of a combination of our pathoblocker with levofloxacin in a murine neutropenic lung infection model and the reduction of LasB protein levels in blood as a proof of target engagement demonstrate the great potential for use as an adjunctive treatment of lung infections in humans.

A single dietary factor, daily consumption of a fermented beverage, can modulate the gut bacteria and fecal metabolites within the same ethnic community.

Our study investigated how a traditional drink called Apong, made from fermented rice, affects the gut and health of the Mishing community in India. We compared two groups of people who drink Apong to a group of people who do not drink it. To accomplish this, we studied the gut bacteria, fecal metabolites, and blood samples of the participants. It was found that the people who drank Apong had higher blood pressure but lower blood sugar and protein levels than people who did not drink it. We also found that the gut microbiome composition of people who drank Apong was different from those who did not drink it. Moreover, people who drank Apong had lower levels of isovaleric acid in their feces. Overall, this study shows that a traditional drink like Apong can affect the gut bacteria of a community.

Clinical characteristics and risk factors of acute lymphoblastic leukemia in children with severe infection during maintenance treatment.

Infection is the most common adverse event of acute lymphoblastic leukemia (ALL) treatment and is also one of the main causes of death. To investigate the clinical characteristics and risk factors of severe infections during the maintenance phase of ALL treatment, we conducted a retrospective study. A total of 181 children were eligible and 46 patients (25.4%) suffered from 51 events of severe infection, most of which occurred in the first half year of the maintenance phase (52.9%). The most common infection was pulmonary infection (86.3%) followed by bloodstream infection (19.6%). The main symptoms of ALL patients with pulmonary infection were fever, cough, and shortness of breath. The main manifestations of computer tomography (CT) were ground glass shadow (56.8%), consolidation shadow (27.3%), and streak shadow (25%). Multivariate binary logistic regression analysis showed that agranulocytosis, agranulocytosis ≥7 days, anemia, and low globulin level were independent risk factors for severe infection during the maintenance phase (all p < 0.05). Taken together, blood routine examinations and protein levels should be monitored regularly for ALL patients in the maintenance phase, especially in the first 6 months. For ALL patients with risk factors, preventive anti-infective or supportive therapies can be given as appropriate to reduce the occurrence of severe infections.

Physiological stress responses of European seabass Dicentrarchus labrax related to changing operations of floating net cages in intensive farming conditions at the Moroccan M'diq bay.

The present study purposed to quantify and compare in-situ the primary and secondary physiological stress responses, related to the operation of floating net-cages changing, in both sub-adults (523 days post hatching) and adults (916 dph) European sea bass Dicentrarchus labrax, under intensive farming conditions in the Moroccan M'diq Bay. Levels of cortisol, glucose, total cholesterol, total protein and lactate, as well as the percentage of hematocrit were measured before and after stress. The results showed significantly elevated levels of cortisol and blood glucose in both age groups, while total cholesterol and protein levels were unaffected. In fact, blood lactate was significantly reduced in sub-adults, while in adults this parameter was not affected by the operation. However, the hematocrit percentages measured after the operation were significantly higher than those found before the operation in both groups of fish, which is linked to the increased rate of oxygen renewal by the new net cages and the lower water temperature inside the cages. With regard to the age-specific response during this essential operation - before and after the operation - plasma cortisol, blood glucose and lactate concentrations, as well as plasma total protein levels, were significantly higher in sub-adults than in adults. It is concluded that aquaculture practices such as changing the aquaculture net-cage could have repercussions in terms of the classic physiological responses to stress in D. labrax. This article is protected by copyright. All rights reserved.

Influence of constant lighting on the morphofunctional state and rhythmostasis of the liver of rats

BACKGROUND: There are evidences that light pollution, which causes melatonin deficiency and disruption of circadian rhythm, is associated with the development of malignant neoplasms of the liver, non-alcoholic fatty liver disease, biliary cirrhosis, and a number of other pathologies of this organ.&#x0D; AIM: The aim of research was to study the features of chronic influence of constant lighting on lability of morphofunctional state of liver of mature Wistar rats and the structure of circadian rhythms of its parameters.&#x0D; MATERIALS AND METHODS: The study was conducted on 80 rats divided into 2 groups: a control group kept under a fixed light regime (light/dark 12/12 h, lights on at 8:00 and off at 20:00), and an experimental group kept under constant lighting 24 h a day. The duration of the experiment was 3 weeks.&#x0D; RESULTS: Its established that influence of constant light led to an increase in the size of hepatocytes and a decrease in nuclear-cytoplasmic ratio, average ploidy and proportion of binuclear hepatocytes, and also to development of fatty degeneration, a decrease in the expression of Bmal1 and Clock, and an increase in the expression of per2 and p53 in hepatocytes. At the same time, there was a decrease in glycogen content in hepatocytes. Dark deprivation also caused an increase in glucose levels, AST activity, and a decrease in blood levels of total protein and albumin. Constant lighting caused a rearrangement of the circadian rhythms of the area of nuclei, the area of the hepatocyte and nuclear-cytoplasmic ratio, Bmal1, per2, Clock expression, and led to destruction of Ki67 and p53 circadian rhythms in hepatocytes. Under conditions of constant lighting, the circadian rhythms of the content of lipids and glycogen in hepatocytes, ALT activity in the blood, and the content of total and direct bilirubin were also destroyed.&#x0D; CONCLUSIONS: It has been established that constant illumination causes a restructuring of the circadian rhythms of a number of studied parameters against the background of morphological and functional changes, indicating a decrease in the adaptive capacity of the liver.

TNFSF14/LIGHT promotes cardiac fibrosis and atrial fibrillation vulnerability via PI3Kγ/SGK1 pathway-dependent M2 macrophage polarisation

BackgroundTumour necrosis factor superfamily protein 14 (TNFSF14), also called LIGHT, is an important regulator of immunological and fibrosis diseases. However, its specific involvement in cardiac fibrosis and atrial fibrillation (AF) has not been fully elucidated. The objective of this study is to examine the influence of LIGHT on the development of myocardial fibrosis and AF.MethodsPCR arrays of peripheral blood mononuclear cells (PBMCs) from patients with AF and sinus rhythm was used to identify the dominant differentially expressed genes, followed by ELISA to evaluate its serum protein levels. Morphological, functional, and electrophysiological changes in the heart were detected in vivo after the tail intravenous injection of recombinant LIGHT (rLIGHT) in mice for 4 weeks. rLIGHT was used to stimulate bone marrow-derived macrophages (BMDMs) to prepare a macrophage-conditioned medium (MCM) in vitro. Then, the MCM was used to culture mouse cardiac fibroblasts (CFs). The expression of relevant proteins and genes was determined using qRT-PCR, western blotting, and immunostaining.ResultsThe mRNA levels of LIGHT and TNFRSF14 were higher in the PBMCs of patients with AF than in those of the healthy controls. Additionally, the serum protein levels of LIGHT were higher in patients with AF than those in the healthy controls and were correlated with left atrial reverse remodelling. Furthermore, we demonstrated that rLIGHT injection promoted macrophage infiltration and M2 polarisation in the heart, in addition to promoting atrial fibrosis and AF inducibility in vivo, as detected with MASSON staining and atrial burst pacing respectively. RNA sequencing of heart samples revealed that the PI3Kγ/SGK1 pathway may participate in these pathological processes. Therefore, we confirmed the hypothesis that rLIGHT promotes BMDM M2 polarisation and TGB-β1 secretion, and that this process can be inhibited by PI3Kγ and SGK1 inhibitors in vitro. Meanwhile, increased collagen synthesis and myofibroblast transition were observed in LIGHT-stimulated MCM-cultured CFs and were ameliorated in the groups treated with PI3Kγ and SGK1 inhibitors.ConclusionLIGHT protein levels in peripheral blood can be used as a prognostic marker for AF and to evaluate its severity. LIGHT promotes cardiac fibrosis and AF inducibility by promoting macrophage M2 polarisation, wherein PI3Kγ and SGK1 activation is indispensable.

CSF1R regulates schizophrenia-related stress response and vascular association of microglia/macrophages

BackgroundMicroglia are known to regulate stress and anxiety in both humans and animal models. Psychosocial stress is the most common risk factor for the development of schizophrenia. However, how microglia/brain macrophages contribute to schizophrenia is not well established. We hypothesized that effector molecules expressed in microglia/macrophages were involved in schizophrenia via regulating stress susceptibility.MethodsWe recruited a cohort of first episode schizophrenia (FES) patients (n = 51) and age- and sex-paired healthy controls (HCs) (n = 46) with evaluated stress perception. We performed blood RNA-sequencing (RNA-seq) and brain magnetic resonance imaging, and measured plasma level of colony stimulating factor 1 receptor (CSF1R). Furthermore, we studied a mouse model of chronic unpredictable stress (CUS) combined with a CSF1R inhibitor (CSF1Ri) (n = 9 ~ 10/group) on anxiety behaviours and microglial biology.ResultsFES patients showed higher scores of perceived stress scale (PSS, p < 0.05), lower blood CSF1R mRNA (FDR = 0.003) and protein (p < 0.05) levels, and smaller volumes of the superior frontal gyrus and parahippocampal gyrus (both FDR < 0.05) than HCs. In blood RNA-seq, CSF1R-associated differentially expressed blood genes were related to brain development. Importantly, CSF1R facilitated a negative association of the superior frontal gyrus with PSS (p < 0.01) in HCs but not FES patients. In mouse CUS+CSF1Ri model, similarly as CUS, CSF1Ri enhanced anxiety (both p < 0.001). Genes for brain angiogenesis and intensity of CD31+-blood vessels were dampened after CUS-CSF1Ri treatment. Furthermore, CSF1Ri preferentially diminished juxta-vascular microglia/macrophages and induced microglia/macrophages morphological changes (all p < 0.05).ConclusionMicroglial/macrophagic CSF1R regulated schizophrenia-associated stress and brain angiogenesis.

The development of blood protein profiles in extremely preterm infants follows a stereotypic evolution pattern

BackgroundPreterm birth is the leading cause of neonatal mortality and morbidity. Early diagnosis and interventions are critical to improving the clinical outcomes of extremely premature infants. Blood protein profiling during the first months of life in preterm infants can shed light on the role of early extrauterine development and provide an increased understanding of maturation after extremely preterm birth and the underlying mechanisms of prematurity-related disorders.MethodsWe have investigated the blood protein profiles during the first months of life in preterm infants on the role of early extrauterine development. The blood protein levels were analyzed using next generation blood profiling on 1335 serum samples, collected longitudinally at nine time points from birth to full-term from 182 extremely preterm infants.ResultsThe protein analysis reveals evident predestined serum evolution patterns common for all included infants. The majority of the variations in blood protein expression are associated with the postnatal age of the preterm infants rather than any other factors. There is a uniform protein pattern on postnatal day 1 and after 30 weeks postmenstrual age (PMA), independent of gestational age (GA). However, during the first month of life, GA had a significant impact on protein variability.ConclusionsThe unified pattern of protein development for all included infants suggests an age-dependent stereotypic development of blood proteins after birth. This knowledge should be considered in neonatal settings and might alter the clinical approach within neonatology, where PMA is today the most dominant age variable.

Racial and Educational Disparities in Cumulative Exposure to Hardships of the 2008 Great Recession and Inflammation.

This cross-sectional analysis examined self-reported economic hardships of the 2008 Great Recession, race/ethnicity, educational attainment, and psychological well-being (PWB) as predictors of systemic inflammatory physiology at midlife. We also tested for differential vulnerability in the relationship between recession hardship and inflammatory physiology by race/ethnicity, education, and PWB. Adults from the Midlife in the United States Refresher sample completed a survey and biomedical assessments after the recession ( n = 592 non-Hispanic White respondents, n = 158 Black/African American respondents, n = 108 respondents with other race/ethnicity). Cumulative recession hardship was the sum of financial, housing, and employment-related events. Outcomes included circulating levels of interleukin 6 and C-reactive protein. General linear regression models tested main effects interactions between primary predictor variables. Educational attainment was inversely associated with recession hardships ( b = -0.18, 95% confidence interval = -0.26 to -0.11, p < .001). Black/African American respondents reported more recession hardships than White respondents ( b = 1.17, 95% confidence interval = 0.67 to 1.68, p < .001). More recession hardships predicted higher levels of interleukin 6 ( b = 0.06, p < .001) and C-reactive protein ( b = 0.04, p = .004). Analyses did not support race/ethnicity, education, and PWB as moderators of the association between recession hardship and inflammatory markers. Race/ethnicity and education independently predicted disparities in cumulative recession hardship exposure. Recession hardship predicted higher blood levels of inflammatory proteins associated with long-term health. The lack of findings for differential vulnerability in the relationship between recession hardship and inflammatory markers by race/ethnicity, education, or PWB was possibly due to the limited sample size.

Effect of different delivery modes on the level of protein, glucose and blood lipids in cord artery and vein blood

To explore whether there are differences in the levels of protein, glucose and blood lipids in umbilical vein and umbilical artery blood of newborns with different delivery modes, and to evaluate their value as indicators of fetal intrauterine nutrition and nutritional support. A total of 89 pairs of mothers and infants who were delivered in Danyang People&apos;s Hospital of Jiangsu Province from June to September 2021 were selected as the study subjects, including 38 cases of spontaneous delivery and 51 cases of cesarean section. The basic information of pregnant women, pregnancy information, newborn delivery and physical examination information were extracted from the medical record information system of the hospital. According to the mode of delivery, HITACHI 7600 automatic biochemical analyzer was used to measure the levels of protein, glucose and blood lipids in umbilical vein and umbilical artery blood, including total protein(TP), albumin(ALB), glucose(GLU), total cholesterol(TC), triglyceride(TG), high density lipoprotein cholesterol(HDL-C), low density lipoprotein cholesterol(LDL-C). The data were statistically analyzed using IBM SPSS Statistics 26.0 statistical software. The levels of TP, ALB, GLU, TC, TG, HDL-C and LDL-C in the umbilical vein blood of the spontaneous delivery group were(56.40±5.83)g/L, (38.41±3.43)g/L, (4.55±1.53)mmol/L, (1.68±0.42)mmol/L, (0.25±0.11)mmol/L, (0.84±0.17)mmol/L and(0.69±0.23)mmol/L, respectively. The levels of TP, ALB, GLU, TC, TG, HDL-C and LDL-C in umbilical artery blood were(56.49±9.91)g/L, (37.72±4.77)g/L, (4.07±1.52)mmol/L, (1.60±0.42)mmol/L, (0.24±0.10)mmol/L, (0.80±0.18)mmol/L and(0.68±0.24)mmol/L, respectively. The levels of TP, ALB, GLU, TC, TG, HDL-C and LDL-C in umbilical vein blood of cesarean section group were(52.08±4.12)g/L, (36.12±2.13)g/L, (3.45±1.16)mmol/L, (1.61±0.39)mmol/L, (0.19±0.08)mmol/L, (0.82±0.18)mmol/L and(0.61±0.20)mmol/L, respectively. The levels of TP, ALB, GLU, TC, TG, HDL-C and LDL-C in umbilical artery blood were(51.49±7.59)g/L, (35.40±3.60)g/L, (3.09±1.15)mmol/L, (1.48±0.40)mmol/L, (0.19±0.08)mmol/L, (0.78±0.18)mmol/L and(0.60±0.20)mmol/L, respectively. The levels of TP, ALB, Glu and TG in cord vein blood and cord artery blood in spontaneous labor group were significantly higher than those in cesarean section group(P&lt;0.05); The levels of Glu, TC, TG and HDL-C in cord vein blood were significantly higher in spontaneous labor group and cesarean section group than those in cord artery blood(P&lt;0.05). The levels of protein, glucose and blood lipids in umbilical vein and umbilical artery blood were different among different delivery modes.

Méningites et encéphalites infectieuses : diagnostic, analyses complémentaires et approche syndromique

AbstractMeningitis and encephalitis (ME), often of infectious origin, are associated with substantial morbidity and mortality. Clinical manifestations are not specific for the causative agent and difficult to evidence in newborns. Early, rapid, and accurate diagnosis is crucial to enable appropriate probabilistic treatment, etiology-driven adjustments, and to minimize complications. Traditional biological diagnosis includes analysis of cerebrospinal fluid (LCS) by white blood cell count, Gram staining, glucose and protein levels, and may be supplemented by other biochemical markers (lactates) and serum procalcitonin.Viruses and bacteria will be sought in the LCS, conventionally by viral PCR for the former and by culture for the latter. In recent years, the diagnosis of CSF infections has moved from a conventional approach to a syndromic approach based on molecular tests that simultaneously detect the presence of several pathogens (viral, bacterial, fungi and parasites). The next step could be a metagenomic approach with integration of host data allowing personalized patient management.

Low-density granulocytes are related to shorter pregnancy duration but not to interferon alpha protein blood levels in systemic lupus erythematosus

BackgroundAn increased risk of pregnancy complications is seen in women with systemic lupus erythematosus (SLE), but the specific immunopathological drivers are still unclear. Hallmarks of SLE are granulocyte activation, type I interferon (IFN) overproduction, and autoantibodies. Here we examined whether low-density granulocytes (LDG) and granulocyte activation increase during pregnancy, and related the results to IFNα protein levels, autoantibody profile, and gestational age at birth.MethodsRepeated blood samples were collected during pregnancy in trimesters one, two, and three from 69 women with SLE and 27 healthy pregnant women (HC). Nineteen of the SLE women were also sampled late postpartum. LDG proportions and granulocyte activation (CD62L shedding) were measured by flow cytometry. Plasma IFNα protein concentrations were quantified by single molecule array (Simoa) immune assay. Clinical data were obtained from medical records.ResultsWomen with SLE had higher LDG proportions and increased IFNα protein levels compared to HC throughout pregnancy, but neither LDG fractions nor IFNα levels differed during pregnancy compared to postpartum in SLE. Granulocyte activation status was higher in SLE relative to HC pregnancies, and it was increased during pregnancy compared to after pregnancy in SLE. Higher LDG proportions in SLE were associated with antiphospholipid positivity but not to IFNα protein levels. Finally, higher LDG proportions in trimester three correlated independently with lower gestational age at birth in SLE.ConclusionOur results suggest that SLE pregnancy results in increased peripheral granulocyte priming, and that higher LDG proportions late in pregnancy are related to shorter pregnancy duration but not to IFNα blood levels in SLE.