Elevated Serum Concentrations Research Articles

Association Between Fluoroquinolones and Major Adverse Cardiovascular Events: A Systematic Review.

Fluoroquinolones (FQs) are routinely administered antibiotics that have demonstrated an increased propensity to cause major adverse cardiovascular events (MACE). We conducted a systematic review aimed to investigate the association between FQ usage and the risk of MACE. A comprehensive literature search was conducted using PubMed, Scopus, and the Cochrane Library from inception to September 2023 to retrieve studies comparing FQ administration with placebo and reporting the occurrence of MACE. Relevant studies that explored the occurrence of MACE, defined as "acute myocardial infarction, stroke, cardiovascular mortality, arrhythmia, or heart failure" with FQ usage were eligible for inclusion. Four studies with a total of 42,808 patients were included. Levofloxacin, moxifloxacin, and gatifloxacin were observed to have an increased propensity to cause MACE, particularly arrhythmias, whereas ciprofloxacin was associated with the lowest risk of causing MACE. Despite the methodological diversity in the included studies, this systematic review uncovered a consistent trend of heightened likelihood of MACE with FQ administration across studies, suggesting that elevated serum concentrations of some FQs may correlate with higher risks of MACE development. This systematic review emphasizes the need for cautious administration of FQs, particularly in patients with a preexisting cardiovascular condition. Routine cardiac monitoring using electrocardiograms is warranted for patients on high doses of FQs to preemptively detect the development of MACE, particularly arrhythmias.

C-reactive protein, cardiovascular issues of an acute-phase protein: an update for theclinician

Inflammation is an important pathogenic factor for the development of atherosclerotic cardiovascular disease. Currently, the most frequently used biomarker reflecting systemic inflammation is C-reactive protein (CRP), an acute-phase protein produced primarily by hepatocytes under the influence of interleukin-6, interleukin-1 beta, and tumor necrosis factor. Growing evidence from epidemiological studies has shown a robust association between elevated serum or plasma CRP concentrations and the incidence of a first cardiovascular adverse event (including acute myocardial infarction, ischemic stroke, and sudden cardiac death) in the general population, as well as recurrence of major adverse cardiovascular events among patients with established disease. The additive value that CRP measurement gives to traditional risk factors is reflected in novel cardiovascular risk calculators and in current intervention regimens, which already consider CRP as a target therapeutic. However, the variations in CRP levels, that depend on sex, ethnicity, hormonal status, and some peculiarities of the measurement assays, must be taken into consideration when deciding to implement CRP as a useful biomarker in the study and treatment of atherosclerotic cardiovascular disease. This review aims to offer an updated vision of the importance of measuring CRP levels as a biomarker of cardiovascular risk beyond the traditional factors that estimate the risk of atherosclerotic disease.

The Effect of Maternal Overweight/Obesity on Serum and Breastmilk Leptin, and Its Associations with Body Composition, Cardiometabolic Health Indices, and Maternal Diet: The BLOOM Study.

In overweight and obese patients, elevated serum and breastmilk leptin concentrations are observed, with serum leptin also being likely affected by the diet. We analyzed serum and breastmilk leptin in normal weight (NW) and overweight/obese (OW/OB) mothers, and evaluated its associations with (1) maternal anthropometric parameters; (2) markers of cardiometabolic health; and (3) the maternal diet. The BLOOM (Breastmilk and the Link to Overweight/Obesity and Maternal diet) study was conducted among 40 women (n = 20 OW/OB; n = 20, NW) who were exclusively or predominantly breastfeeding for 15.5 ± 1.2 (OW/OB group (0.99)) weeks. We collected 24 h breastmilk and fasting blood samples for leptin analysis by ELISA. Maternal dietary habits were evaluated using a 3-day dietary record and food frequency questionnaire, which were used to calculate the Polish-adapted Mediterranean Diet score. Maternal anthropometric measurements and DEXA scans were performed, and anthropometric and cardiometabolic indices were calculated. The OW mothers had 1.4 times higher serum levels, while OB mothers had 4.5 and 6.2 higher serum and breastmilk leptin levels, respectively, in comparison to the NW mothers. The FM% was correlated with serum and breastmilk leptin levels (r = 0.878, r = 0.638). Serum leptin was associated with markers of cardiometabolic health such as AIP, CMI, and VAI in the NW mothers, and with LAP in the OW/OB mothers. Higher energy, fructose intake and adherence to the Mediterranean diet were associated with serum leptin in the NW mothers (β = 0.323, 0.039-0.608; β = 0.318, 0.065-0.572; β = 0.279, 0.031-0.528); meanwhile, higher adherence to the Mediterranean diet could protect against elevated breastmilk leptin concentrations in OW/OB mothers (β = -0.444, -0.839--0.050), even after adjustment for FM%. Our results suggest a potential association between maternal serum leptin concentrations and cardiometabolic health. In addition, we confirm the importance of healthy dietary patterns in the improvement of breastmilk composition.

Identification of Serum Interleukin-22 as Novel Biomarker in Pulmonary Hypertension: A Translational Study.

Growing evidence suggests the crucial involvement of inflammation in the pathogenesis of pulmonary hypertension (PH). The current study analyzed the expression of interleukin (IL)-17a and IL-22 as potential biomarkers for PH in a preclinical rat model of PH as well as the serum levels in a PH patient collective. PH was induced by monocrotalin (60 mg/kg body weight s.c.) in 10 Sprague Dawley rats (PH) and compared to 6 sham-treated controls (CON) as well as 10 monocrotalin-induced, macitentan-treated rats (PH_MAC). Lung and cardiac tissues were subjected to histological and immunohistochemical analysis for the ILs, and their serum levels were quantified using ELISA. Serum IL levels were also measured in a PH patient cohort. IL-22 expression was significantly increased in the lungs of the PH and PH_MAC groups (p = 0.002), whereas increased IL17a expression was demonstrated only in the lungs and RV of the PH (p < 0.05) but not the PH_MAC group (p = n.s.). The PH group showed elevated serum concentrations for IL-22 (p = 0.04) and IL-17a (p = 0.008). Compared to the PH group, the PH_MAC group demonstrated a decrease in IL-22 (p = 0.021) but not IL17a (p = n.s.). In the PH patient collective (n = 92), increased serum levels of IL-22 but not IL-17a could be shown (p < 0.0001). This elevation remained significant across the different etiological groups (p < 0.05). Correlation analysis revealed multiple significant relations between IL-22 and various clinical, laboratory, functional and hemodynamic parameters. IL-22 could serve as a promising inflammatory biomarker of PH with potential value for initial diagnosis, functional classification or even prognosis estimation. Its validation in larger patients' cohorts regarding outcome and survival data, as well as the probability of promising therapeutic target structures, remains the object of further studies.

The impact of brominated flame retardants (BFRs) on pulmonary function in US adults: a cross-sectional study based on NHANES (2007–2012)

Brominated flame retardants (BFRs) are a group of chemicals widely used in various applications to prevent or slow down the spread of fire. However, they have adverse effects on human health. There is a relative scarcity of population-based studies regarding BFRs, particularly their impact on the respiratory system. This study aimed to investigate the influence of BFRs on pulmonary function using data from the National Health and Nutrition Examination Survey. The study found that elevated serum concentrations of certain BFRs were associated with pulmonary ventilatory dysfunction. Adjusted analyses revealed positive correlations between PBDE47, PBDE183, and PBDE209 concentrations and ventilatory dysfunction. The analysis of mixed BFRs showed a positive relationship with pulmonary ventilation dysfunction, with PBDE47 making the most significant contribution. Our study demonstrates that both individual and combined BFRs exposure can lead to impaired pulmonary ventilation function. These findings provide evidence of the adverse effects of BFRs on lung function, emphasizing the importance of further investigating the potential health consequences of these compounds. Further large-scale longitudinal studies are needed to investigate this relationship in the future.

Bacterial antigens and asthma: a comparative study of common respiratory pathogenic bacteria

Objective: In a previous study we have shown that, in the presence of interleukin (IL)-33, repeated, per-nasal challenge of murine airways with Streptococcus pneumoniae (S. pneumoniae) organisms induces human asthma-like airways inflammation. It is not clear, however, whether this effect is unique or manifest in response to other common respiratory pathogens.Methods: To explore this, airways of BALB/c mice were repeatedly challenged per-nasally with formaldehyde-inactivated bacterial bodies in the presence or absence of murine recombinant IL-33. Serum concentrations of S.pneumoniae, Moraxella catarrhalis (M.catarrhalis) and Haemophilus influenzae (H.influenzae) lysates-specific IgE were measured in patients with asthma and control subjects.Results: We showed that in the presence of IL-33, repeated, per-nasal airways exposure to the bodies of these bacteria induced airways hyperresponsiveness (AHR) in the experimental mice. This was accompanied by cellular infiltration into bronchoalveolar lavage fluid (BALF), eosinophilic infiltration and mucous hypertrophy of the lung tissue, with elevated local expression of some type 2 cytokines and elevated, specific IgG and IgE in the serum. The precise characteristics of the inflammation evoked by exposure to each bacterial species were distinguishable.Conclusions: These results suggest that in the certain circumstances, inhaled or commensal bacterial body antigens of both Gram-positive (S. pneumoniae) and Gram-negative (M. catarrhalis and H. influenzae) respiratory tract bacteria may initiate type 2 inflammation typical of asthma in the airways. In addition, we demonstrated that human asthmatic patients manifest elevated serum concentrations of M.catarrhalis- and H.influenzae-specific IgE.

Role of substance P in cerebral edema and association with an estimated specific gravity of the brain and an outcome prediction in post-traumatic cerebral edema

PurposeThe study aims to evaluate the role of substance P in cerebral edema and outcomes associated with acute TBI. MethodPatients with acute TBI who presented within 6 h and a CT scan showed predominantly cerebral edema were included in the study. Substance P level was assessed from a serum sample collected within 6 h of trauma. We also evaluated the brain-specific gravity using the Brain View software. ResultA total of 160 (128 male) patients were recruited. The median serum substance P concentration was 167.89 (IQR: 101.09–238.2). Substance P concentration was high in the early hours after trauma (p = 0.001). The median specific gravity of the entire brain was 1.04. Patients with a low Glasgow coma scale (GCS) at admission had a high concentration of the substance P. In the univariate analysis, low GCS, elevated serum concentrations of substance P level, high Rotterdam grade, high cerebral edema grade, a high international normalized ratio value, and high blood sugar levels were associated with poor outcomes at six months. In logistic regression analysis, low GCS at admission, high cerebral edema grade, and elevated blood sugar level were strongly associated with poor outcomes at six months. The area under the receiver operating characteristic curve was 0.884 (0.826–0.941). ConclusionSerum substance P is strongly associated with the severity of cerebral edema after TBI. However, brain-specific gravity does not directly correlate with posttraumatic cerebral edema severity. Serum substance P does not influence the clinical outcome of traumatic brain injury.

The role of matrix metalloproteinase-2 and miR-196a2 in bronchial asthma pathogenesis and diagnosis

BackgroundBronchial asthma is a persistent inflammatory respiratory condition that restricts the passage of air and causes hyperresponsiveness. Chronic asthma can be classified into three categories: mild, moderate, and severe. Remodeling took place as the extracellular matrix accumulated in the walls of the airways. Inflammation occurs as a result of the damage caused by matrix metalloproteinase-2 (MMP-2) to basement membrane type IV collagen. The severity of asthma may be associated with miR-196a2. The objective of our study was to investigate the underlying mechanisms and clinical relevance of miR-196a2 and MMP-2 serum levels in relation to the severity of asthma. MethodsThis study recruited 85 controls and 95 asthmatics classified as mild, moderate, or severe. Expression of miR-196a2 was measured by quantitative reverse transcriptase PCR. Using the enzyme-linked immunosorbent assay (ELISA), MMP-2, IL-6, and total immunoglobulin E (IgE) levels in the serum of asthmatics of various grades were compared to a control group. MMP-2's diagnostic and prognostic potential was determined using ROC curve analysis. This study also measured blood Eosinophils and PFTs. We examined MMP-2's connections with IgE, blood Eosinophils, and PFTs. ResultsThe current investigation found that miR-196a2 expression was significantly higher in the control group than in asthmatic patients as a whole. The study found that severe asthmatics had higher MMP-2, IL-6, and IgE serum levels than healthy controls. We identified the MMP-2 serum concentration cutoff with great sensitivity and specificity. Significant relationships between MMP-2 serum level and miR-196a2 expression in the patient group with severe asthmatics were found. The MMP-2, IL-6, and IgE serum levels were considerably higher in mild, moderate, and severe asthmatics than controls. The miR-196a2 expression and MMP-2 serum concentration correlated positively with IgE and blood eosinophils % and negatively with all lung function tests in the asthmatic patient group.Conclusion: the study revealed that the elevated miR-196a2 expression and serum concentration of MMP-2, IL-6, and IgE associated with elevated blood eosinophils % is associated with pathophysiology and degree of asthma severity. The miR-196a2 expression and MMP-2 serum concentration have a promising diagnostic and prognostic ability in bronchial asthma.

Effects of glycyrrhiza polysaccharides on growth performance, meat quality, serum parameters and growth/meat quality-related gene expression in broilers.

With growing restrictions on the use of antibiotics in animal feed, plant extracts are increasingly favored as natural feed additive sources. Glycyrrhiza polysaccharide (GP), known for its multifaceted biological benefits including growth promotion, immune enhancement, and antioxidative properties, has been the focus of recent studies. Yet, the effects and mechanisms of GP on broiler growth and meat quality remain to be fully elucidated. This study aimed to investigate the effects of GP on growth, serum biochemistry, meat quality, and gene expression in broilers. The broilers were divided into five groups, each consisting of five replicates with six birds. These groups were supplemented with 0, 500, 1,000, 1,500, and 2,000 mg/kg of GP in their basal diets, respectively, for a period of 42 days. The results indicated that from day 22 to day 42, and throughout the entire experimental period from day 1 to day 42, the groups receiving 1,000 and 1,500 mg/kg of GP showed a significant reduction in the feed-to-gain ratio (F:G) compared to the control group. On day 42, an increase in serum growth hormone (GH) levels was shown in groups supplemented with 1,000 mg/kg GP or higher, along with a significant linear increase in insulin-like growth factor-1 (IGF-1) concentration. Additionally, significant upregulation of GH and IGF-1 mRNA expression levels was noted in the 1,000 and 1,500 mg/kg GP groups. Furthermore, GP significantly elevated serum concentrations of alkaline phosphatase (AKP) and globulin (GLB) while reducing blood urea nitrogen (BUN) levels. In terms of meat quality, the 1,500 and 2,000 mg/kg GP groups significantly increased fiber density in pectoral muscles and reduced thiobarbituric acid (TBA) content. GP also significantly decreased cooking loss rate in both pectoral and leg muscles and the drip loss rate in leg muscles. It increased levels of linoleic acid and oleic acid, while decreasing concentrations of stearic acid, myristic acid, and docosahexaenoic acid. Finally, the study demonstrated that the 1,500 mg/kg GP group significantly enhanced the expression of myogenin (MyoG) and myogenic differentiation (MyoD) mRNA in leg muscles. Overall, the study determined that the optimal dosage of GP in broiler feed is 1,500 mg/kg.

Biomarkers of Brain Ischemia (Review)

Introduction. Strokes remain the second leading cause of death and the third leading cause of disability. Additional serum biomarker testing should be used to better diagnose transient ischemic attack (TIA), but most neurospecific biomarkers have low prognostic specificity and sensitivity. Timely identification of TIA and differential diagnosis of stroke in the first hour will ensure a shorter period of patient recovery and reduce the risk of mortality and disability. Serum biomarker studies should be included to overcome the difficulty of diagnosing TIA.Text. Neurospecific biomarkers such as S100B, GFAP, and NSE are used to diagnose acute ischemic damage to glial cells and neurons. S100B and GFAP are detected in astrocytes and NSE in neurons and cells of the neuroendocrine system. Elevated serum concentrations of these biomarkers are associated with various pathological conditions such as strokes and brain injuries and other central nervous system (CNS) lesions. Dynamic monitoring of biomarker concentrations makes it possible to evaluate the efficacy of the ongoing therapy and to identify predictors of patient deterioration for prompt correction of therapeutic procedures. To create a diagnostic panel it is necessary to study metabolic processes in ischemic tissue, taking into account concomitant diagnoses and results of neuroimaging, and to use breakthrough advances in machine learning and big data.Conclusion. The review showed that none of the assessed biomarkers can be recommended for the diagnosis of cerebral circulation disorders, but the combination of several neurospecific biomarkers can significantly improve diagnostic efficiency and find application in the differential diagnosis of stroke, intracranial hematoma, and other brain lesions for the purpose of early pharmacotherapy of CNS lesions and as surrogate endpoints during clinical trials.

P-23 Insulin autoimmune syndrome possibly induced by Alpha-Lipoic acid

Abstract Introduction Insulin autoimmune syndrome (IAS) is a relative rare cause of hypoglycemia due to the presence of extremely high circulating insulin levels and elevated serum concentrations of autoantibodies to human insulin despite no prior exposure to exogenous insulin, insulin analogues or oral hypoglycemic agents. It is characterized by repeated fasting hypoglycemia or episodes of hypoglycemia late after meals in non-diabetic, non-acutely ill patients. Increasing the titer of insulin autoantibodies and immune reactive insulin occurs owing to both genetic influences and environmental triggers such as medication, genetic instability and other factors. It is associated with the use of drugs comprising sulfhydryl groups, such as methimazole, clopidogrel and alpha lipoic acid, mostly. Insulin autoantibodies appear a few weeks after the exposure of sulfhydryl radicals. Here, we summarize the case of IAS caused by drug administration. Clinical Case A 60-year-old female patient who has a history of migraine for 30 years was referred to our hospital for feeling of hunger, dizziness, sweating, tremor, and palpitations for 1 month. These symptoms had commenced episodically, soon after starting 600 mg/day of alpha lipoic acid. She was diagnosed with hypoglycemia based on a plasma glucose concentration of 31 mg/dL. There was no personal or family history of diabetes mellitus, or previous use of oral hypoglycemic drugs such as sulfonylureas or exogenous insulin. No abnormality was detected in the systemic examination. She had no smoking and alcohol abuse. Her regular medication was tricyclic antidepressant (amitriptyline). Laboratory results are presented in Table 1. On our evalution, the serum levels of insulin, C-peptide, and anti-insulin antibody titers were inappropriately elevated in the presence of hypoglycemia, confirming the diagnosis of hyperinsulinemic hypoglycemia. Thyroid function, human growth hormone, insulin growth factor-1 (IGF-1), and cortisol result were within normal limits. Screening for antinuclear factor, serum protein electrophoresis, serology for viral hepatitis, and other autoimmune diseases were negative. Insulinoma was excluded with computed tomography. In light of the above results, a diagnosis of IAS was made with possible alpha lipoic acid. Because, alpha lipoic acid was the only medication being taken associated with a sulfhydryl group. The patient was prescribed oral methylprednisolone (32 mg once daily), alpha lipoic acid was withdrawn. Hypoglycemia did not occur after methylprednisolone treatment of follow-up. Methylprednisolone treatment was tapered to 4 mg once daily within 2 months. The insulin, and anti-insulin antibody titers had decreased. Conclusion We report a rare case of IAS. Sulfhydryl group containing drugs such as alpha lipoic acid might induce or exacerbate hypoglycemia in patients with a history of IAS. For this reason, the use of alpha lipoic acid should be questioned in patients with IAS. Table 1. Laboratory test results

Exosomes derived from mesenchymal stem cells attenuate NLRP3-related pyroptosis in autoimmune premature ovarian insufficiency via the NF-κB pathway

Research questionWhat is the effect of exosomes derived from bone marrow mesenchymal stem cells (MSC-Exos) on the pyroptosis and recovery of granulosa cells in autoimmune premature ovarian insufficiency (POI)? DesignIn vitro, KGN cells were exposed to interferon-gamma to simulate immune injury. Samples were collected after a 48 h incubation with MSC-Exos (30 μg/ml). The cell viability, secretion of oestrogen and expression of key molecules in pyroptosis and the nuclear factor kappa B (NF-κB) pathway were tested. In vivo, the BALB/c mouse model of autoimmune POI model induced by zona pellucida glycoprotein 3 was used. Fertility testing and sample collection were applied 4 weeks after the ovarian subcapsular injection of MSC-Exos (150 μg for each ovary). Hormone concentration measurements, follicle counting and pyroptotic pathway analyses were conducted for each group. ResultsIn vitro, MSC-Exos significantly promoted the proliferation rate and secretion of oestrogen, while at the same time suppressing apoptosis and pyroptosis. In vivo, exosomal treatment normalized the irregular oestrous cycles, rescued the follicular loss and increased the pregnancy rate and number of offspring in POI mice. Elevated serum concentrations of oestrogen and anti-Müllerian hormone, as well as decreased concentrations of FSH and interleukin-1β, were shown. Furthermore, MSC-Exos down-regulated the expression of the NLRP3/Casp1/GSDMD pathway and inhibited activation of the NF-κB pathway. ConclusionsThese findings demonstrate for the first time that MSC-Exos exert a significant effect on restoring ovarian function in autoimmune POI in vivo and in vitro by suppressing the NLRP3/Casp1/GSDMD pathway and pyroptosis. The NF-κB pathway may contribute to the regulation of NLRP3-related pyroptosis.

Clinical and immunological features of 55 adult patients with selective IgG4 subclass deficiencies. Running title: IgG4 deficiency in adults: Clinical &amp; immunological features

Aim: Despite intensive research on elevated IgG4 concentrations in serum, little is known about the importance of selective IgG4 subclass deficiency. We investigated the clinical and immunological characteristics of 55 patients with selective IgG4 subclass deficiency. Materials and methods: IgG subclass analyses performed in our hospital over 3 years were examined. The clinical features of patients with selective IgG4 subclass deficiency were reviewed, and the definitive diagnoses and the reasons for IgG subclass analysis were recorded. Results: Of 1675 IgG subclass analyses performed, 55 were indicative of selective IgG4 subclass deficiency. The final diagnoses associated with selective IgG4 subclass deficiency were variable. The most common clinical finding was recurrent infections (33 patients, 60%), and most had upper respiratory tract infections (18 patients, 54.5%). Allergic diseases were noted in 25 patients (45.4%) and were the second most common conditions. Allergic rhinitis was the most frequent allergic disease. Autoimmune diseases were noted in 18 patients (32.7%), Hashimoto thyroiditis being the most frequent. Conclusion: This is the first study of adult selective IgG4 subclass deficiency at a single tertiary medical center in Turkey. In patients with IgG4 deficiency, while the primary concern is the presence of recurrent infections, consideration should also be given to allergic and autoimmune diseases.

Abnormal hypothalamic functional connectivity and serum arousal-promoting neurotransmitters in insomnia disorder patients: a pilot study.

The present study aimed to investigate the functional connectivity (FC) of the anterior and posterior hypothalamus with the whole brain in insomnia disorder (ID) patients. Additionally, we explored the relationship between FC values and serum levels of arousal-promoting neurotransmitters (orexin-A and histamine) in ID patients. This study enrolled 30 ID patients and 30 age- and gender-matched healthy controls. Resting-state functional magnetic resonance imaging (RS-fMRI) was employed to assess the FC of the anterior and posterior hypothalamus with the whole brain. Serum concentrations of orexin-A and histamine were measured using enzyme-linked immunosorbent assay (ELISA). Moreover, Spearman correlation analysis was conducted to investigate the relationship between FC values and serum levels of arousal-promoting neurotransmitters in ID patients. Our findings showed decreased FC between the posterior hypothalamus and several brain regions including the bilateral orbital superior frontal gyrus, the bilateral angular gyrus, the right anterior cingulate cortex, the left precuneus, and the right medial superior frontal gyrus in ID patients. Additionally, decreased FC was observed between the anterior hypothalamus and the right anterior cingulate cortex among ID patients. Compared to the healthy controls, ID patients showed significantly elevated serum concentrations of orexin-A and histamine. Furthermore, we identified a positive correlation between the FC of the right medial superior frontal gyrus with posterior hypothalamus and histamine levels in ID patients. ID patients exhibited aberrant FC in brain regions related to sleep-wake regulation, particularly involving the default mode network and anterior cingulate cortex, which may correlate with the peripheral levels of histamine. These findings contribute to our understanding of the potential neuroimaging and neurohumoral mechanism underlying ID patients.

Deoxycholic Acid, a Secondary Bile Acid, Increases Cardiac Output and Blood Pressure in Rats.

Deoxycholic acid (DCA) is a secondary bile acid produced by gut bacteria. Elevated serum concentrations of DCA are observed in cardiovascular disease (CVD). We hypothesized that DCA might influence hemodynamic parameters in rats. The concentration of DCA in systemic blood was measured with liquid chromatography coupled with mass spectrometry. Arterial blood pressure (BP), heart rate (HR) and echocardiographic parameters were evaluated in anesthetized, male, 3-4-month-old Sprague-Dawley rats administered intravenously (IV) or intracerebroventricularly (ICV) with investigated compounds. Mesenteric artery (MA) reactivity was tested ex vivo. The baseline plasma concentration of DCA was 0.24 ± 0.03 mg/L. The oral antibiotic treatment produced a large decrease in the concentration. Administered IV, the compound increased BP and HR in a dose-dependent manner. DCA also increased heart contractility and cardiac output. None of the tested compounds-prazosin (an alpha-blocker), propranolol (beta-adrenolytic), atropine (muscarinic receptor antagonist), glibenclamide (K-ATP inhibitor) or DY 268 (FXR antagonist), glycyrrhetinic acid (11HSD2 inhibitor)-significantly diminished the DCA-induced pressor effect. ICV infusion did not exert significant HR or BP changes. DCA relaxed MAs. Systemic vascular resistance did not change significantly. DCA elevates BP primarily by augmenting cardiac output. As a metabolite derived from gut bacteria, DCA potentially serves as a mediator in the interaction between the gut microbiota and the host's circulatory system.

Serum β-synuclein, neurofilament light chain and glial fibrillary acidic protein as prognostic biomarkers in moderate-to-severe acute ischemic stroke

We aimed to assess the prognostic value of serum β-synuclein (β-syn), neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) in patients with moderate-to-severe acute ischemic stroke. We measured β-syn, GFAP and NfL in serum samples collected one day after admission in 30 adult patients with moderate-to-severe ischemic stroke due to middle cerebral artery (MCA) occlusion. We tested the associations between biomarker levels and clinical and radiological scores (National Institute of Health Stroke Scale scores, NIHSS, and Alberta Stroke Program Early CT Score, ASPECTS), as well as measures of functional outcome (modified Rankin Scale, mRS). Serum biomarkers were significantly associated with ASPECTS values (β-syn p = 0.0011, GFAP p = 0.0002) but not with NIHSS scores at admission. Patients who received mechanical thrombectomy and intravenous thrombolysis showed lower β-syn (p = 0.029) und NfL concentrations (p = 0.0024) compared to patients who received only mechanical thrombectomy. According to median biomarker levels, patients with high β-syn, NfL or GFAP levels showed, after therapy, lower clinical improvement (i.e., lower 24-h NIHSS change), higher NIHSS scores during hospitalization and higher mRS scores at 3-month follow-up. Elevated serum concentrations of β-syn (p = 0.016), NfL (p = 0.020) or GFAP (p = 0.010) were significantly associated with 3-month mRS of 3–6 vs. 0–2 even after accounting for age, sex and renal function. In patients with moderate-to-severe acute ischemic stroke, serum β-syn, NfL and GFAP levels associated with clinical and radiological scores at different timepoints and were able to predict short- and middle-term clinical outcomes.

Distinct mode of action of a highly stable, engineered phage lysin killing Gram-negative bacteria.

Engineered lysins are considered as highly promising alternatives for antibiotics. Our previous screening study using VersaTile technology identified 1D10 as a possible lead compound with activity against Acinetobacter baumannii strains under elevated human serum concentrations. In this manuscript, we reveal an unexpected mode of action and exceptional thermoresistance for lysin 1D10. Our findings shed new light on the development of engineered lysins, providing valuable insights for future research in this field.

Anti-inflammatory and Antioxidant Effects of Grapefruit Juice on Ulcerative Colitis induced by Acetic Acid in Rats

Grapefruit is commonly consumed around the world due to its nutritional and medicinal properties. Ulcerative colitis (UC) accounts for an inflammatory bowel disease (IBD) accompanied by irritation, recurrent inflammation, and ulceration of the colon's mucosa. Our objective was to assess the antiinflammatory and antioxidant impacts of grapefruit juice (GFJ) in rat with UC induced by acetic acid (AA). There were five groups made up of 35 mature male rats. Group 2 served as a positive control with UC, whereas group 1 was preserved as a negative control. For 8 weeks, groups 3, 4, and 5 received UC while also given 2.5, 5 or 10% of GFJ orally. Feed efficiency ratio (FER), body weight growth (BWG), and feed intake (FI) were computed. From rat eye orbital plexuses blood samples were taken to separate the serum after centrifugation. The aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activity were assessed utilizing serum samples. The antioxidant enzymes catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD) in serum were quantified. Serum inflammatory cytokines as tumor necrosis factor alpha (TNFα), interleukin 1 β (IL1 β), IL6 and IL8, as well as triglycerides (TG) and total cholesterol (TC) were measured. In liver homogenate, glutathione (GSH) and malondialdehyde (MDA) were determined. Additionally, histopathology of the colon was accomplished. Our findings specified that GFJ at 10% significantly decreased FI, BWG and FER, cytokines TNFα, IL1 β, IL6 and IL8 and TC and TG. Relative to the positive controls, the rats treated with GFJ exhibited elevated serum concentrations of SOD, GPx, and CAT enzymes. Liver GSH was elevated and MDA was reduced. Histopathological examination of the colon showed that GFJ at 10% reduced ulcerative colitis. Because grapefruit juice has strong anti-inflammatory and antioxidant characteristics and reduces oxidative stress and inflammation in rats, grapefruit juice, at a concentration of 10%, likely protects against ulcerative colitis. Patients with ulcerative colitis may find it helpful to consume grapefruit juice as a beverage.

Clinical Applicability of Tissue Polypeptide Antigen and CA-125 in Gynecological Malignancies.

Nowadays there still is no sufficient screening tool for ovarian and uterine cancer. The current study aimed to investigate whether cancer antigen 125 (CA-125), tissue polypeptide antigen (TPA) or the combination of both markers are able to act as screening tools for ovarian or uterine cancer. A total of 275 blood samples from different cohorts (ovarian cancer, uterine cancer, benign control group) were prospectively drawn and analyzed. Established biomarkers TPA and CA-125 showed elevated serum concentrations in patients with malignant tumors as compared to healthy women and women with benign diseases. In ROC curve analyses, both biomarkers were well able to discriminate between malignant and healthy, benign or overall non-malignant cases in the whole sample, with AUCs of 0.842 and above. While TPA was the best diagnostic marker in patients with uterine cancer, CA 125 was the best in patients with ovarian cancer. TPA and CA-125 both showed promising results for the detection of gynecologic malignancies. The combination of CA-125 and TPA did not improve sensitivity in comparison to single markers.

Serum Selenium-Binding Protein 1 (SELENBP1) in Burn Injury: A Potential Biomarker of Disease Severity and Clinical Course.

Oxidative stress, systemic inflammation, and metabolic derangements are hallmarks of burn pathophysiology. Severely burned patients are highly susceptible to infectious complications. Selenium-binding protein 1 (SELENBP1) modulates intracellular redox homeostasis, and elevated serum concentrations have been associated with adverse clinical outcomes in trauma patients. We hypothesized that serum SELENBP1 at hospital admission and during hospitalization may constitute a meaningful biomarker of disease severity and the clinical course in burn injury, with pulmonary infection as primary endpoint. To this end, we conducted a prospective cohort study that included 90 adult patients admitted to the Burn Center of the University Hospital Zurich, Switzerland. Patients were treated according to the local standard of care, with high-dose selenium supplementation during the first week. Serum SELENBP1 was determined at nine time-points up to six months postburn and the data were correlated to clinical parameters. SELENBP1 was initially elevated and rapidly declined within the first day. Baseline SELENBP1 levels correlated positively with the Abbreviated Burn Severity Index (ABSI) (R = 0.408; p < 0.0001). In multiple logistic regression, a higher ABSI was significantly associated with increased pulmonary infection risk (OR, 14.4; 95% CI, 3.2-88.8; p = 0.001). Similarly, baseline SELENBP1 levels constituted a novel but less accurate predictor of pulmonary infection risk (OR, 2.5; 95% CI, 0.7-8.9; p = 0.164). Further studies are needed to explore the additional value of serum SELENBP1 when stratifying patients with respect to the clinical course following major burns and, potentially, for monitoring therapeutic measures aimed at reducing tissue damage and oxidative stress.