Blood Levels Research Articles

Genetic variations in anti-diabetic drug targets and COPD risk: evidence from mendelian randomization

BackgroundPrevious research has emphasized the potential benefits of anti-diabetic medications in inhibiting the exacerbation of Chronic Obstructive Pulmonary Disease (COPD), yet the role of anti-diabetic drugs on COPD risk remains uncertain.MethodsThis study employed a Mendelian randomization (MR) approach to evaluate the causal association of genetic variations related to six classes of anti-diabetic drug targets with COPD. The primary outcome for COPD was obtained from the Global Biobank Meta-analysis Initiative (GBMI) consortium, encompassing a meta-analysis of 12 cohorts with 81,568 cases and 1,310,798 controls. Summary-level data for HbA1c was derived from the UK Biobank, involving 344,182 individuals. Positive control analysis was conducted for Type 2 Diabetes Mellitus (T2DM) to validate the choice of instrumental variables. The study applied Summary-data-based MR (SMR) and two-sample MR for effect estimation and further adopted colocalization analysis to verify evidence of genetic variations.ResultsSMR analysis revealed that elevated KCNJ11 gene expression levels in blood correlated with reduced COPD risk (OR = 0.87, 95% CI = 0.79–0.95; p = 0.002), whereas an increase in DPP4 expression corresponded with an increased COPD incidence (OR = 1.18, 95% CI = 1.03–1.35; p = 0.022). Additionally, the primary method within MR analysis demonstrated a positive correlation between PPARG-mediated HbA1c and both FEV1 (OR = 1.07, 95% CI = 1.02–1.13; P = 0.013) and FEV1/FVC (OR = 1.08, 95% CI = 1.01–1.14; P = 0.007), and a negative association between SLC5A2-mediated HbA1c and FEV1/FVC (OR = 0.86, 95% CI = 0.74–1.00; P = 0.045). No colocalization evidence with outcome phenotypes was detected (all PP.H4 < 0.7).ConclusionThis study provides suggestive evidence for anti-diabetic medications' role in improving COPD and lung function. Further updated MR analyses are warranted in the future, following the acquisition of more extensive and comprehensive data, to validate our results.

Compatibility study of topical 0.25% hypericin (HyBryteTM) application in subjects with mycosis fungoides: Results of the HPN‐CTCL‐02 study

AbstractBackgroundHyBryteTM is a photodynamic therapy of topical hypericin that has recently been shown to be safe and efficacious in early stage cutaneous T‐cell lymphoma (CTCL). However, its efficacy, absorption, and effect on heart function parameters in patients who require greater HyBryteTM exposure is unknown.ObjectivesThe primary objectives in this study were to assess hypericin blood levels using a validated detection method with a cut‐off value of 0.05 ng/mL and to determine if topical HyBryteTM induces any electrocardiogram (EKG) changes during 8 weeks of treatment. A secondary endpoint of this study was to assess the effectiveness of HyBryteTM in this patient population as well as assessing a different additional light device than the one used in the Phase 3 HPN‐CTCL‐01/fluorescent light activated synthetic hypericin trial also entitled “A phase 3 multicenter randomised placebo‐controlled study to determine the efficacy of topical hypericin and light irradiation for the treatment of cutaneous T‐cell lymphoma”.MethodsA confirmatory, prospective, open‐label, single‐centre, interventional study focused on stage IB and IIA mycosis fungoides with more than 10% of their body surface areas involved was performed.ResultsHypericin concentration in K2EDTA whole blood samples collected before and after light activation at Weeks 4, 6 and 8 showed an average blood concentration of 0.13 ng/mL and achieved steady state by Week 4. EKGs were examined for clinical changes at each study visit, including changes in QT intervals and correction of heart rates. No significant clinical changes in EKGs were observed.ConclusionsHypericin does not appear to be significantly absorbed through the skin nor cause significant cardiac changes overall or prolong the QT interval when applied topically. A larger study is necessary to clearly define these results.

Determination of anti-Müllerian hormone levels in blood and urine in fertile cats

In recent years, blood anti-Müllerian hormone (AMH) levels have been investigated in female animals to diagnose many conditions, such as the presence of ovarian tissue, follicle reserve, and granulosa cell tumors. Since blood collection is an invasive method, diagnosis with a non-invasive method is important in terms of practicality and animal welfare. This study aimed to investigate the presence of AMH in cat urine and determine whether a correlation exists between blood and urine AMH levels. In addition, it was aimed at revealing whether there was a change in blood and urine AMH levels according to ovarian follicle distribution. Twenty-seven healthy, fertile female cats in the follicular phase were included. Following blood and urine sample collection, a routine ovariohysterectomy was performed. Histological analysis of the removed ovarian tissue was used to determine ovarian follicle types. While both AMH and estrogen levels were determined in blood samples, only AMH levels were investigated in urine samples. Blood AMH levels averaged 10.61 ± 0.75 ng/mL (range: 5–16 ng/mL), while urine AMH levels averaged 5.67 ± 0.91 ng/mL (range: 0.2–13 ng/mL). While urinary AMH level was <1 ng/mL in 7 cats, urinary AMH was >1 ng/mL in all remaining cats. While the study demonstrated AMH excretion in urine, no correlation was found between blood and urine AMH values. However, a significant positive correlation was observed between blood AMH levels and serum estrogen levels (P < 0.001). These findings suggest that urinary AMH may be a product of proteolytic degradation, potentially leading to inaccurate estimations of ovarian activity based solely on urine AMH levels.

The role of M1/M2 macrophage polarization in primary Sjogren’s syndrome

BackgroundThe purpose of this study was to investigate the role of macrophage polarization in the pathogenesis of primary Sjogren’s syndrome (pSS).MethodsPeripheral venous blood samples were collected from 30 patients with pSS and 30 healthy controls. Minor salivary gland samples were abtainted from 10 of these patients and 10 non-pSS controls whose minor salivary gland didn’t fulfill the classification criteria for pSS. Enzyme-linked immuno sorbent assay was used to examine the serum concentration of M1/M2 macrophage related cytokines (TNF-a, IL-6, IL-23, IL-4, IL-10 and TGF-β). Flow cytometry was used to examine the numbers of CD86+ M1 macrophages and CD206+ M2 macrophages in peripheral blood mononuclear cells (PBMCs). Immunofluorescence was used to test the infiltration of macrophages in minor salivary glands.ResultsThis study observed a significant increase in pSS patients both in the numbers of M1 macrophages in peripheral blood and serum levels of M1-related pro-inflammatory cytokines (IL-6, IL-23 and TNF-α). Conversely, M2 macrophages were downregulated in the peripheral blood of pSS patients. Similarly, in the minor salivary glands of pSS patients, the expression of M1 macrophages was increased, and that of M2 macrophages was decreased. Furthermore, a significantly positive correlation was found between the proportions of M1 macrophages in PBMCs and serum levels of IgG and RF.ConclusionsThis study reveals the presence of an significant imbalance in M1/M2 macrophages in pSS patients. The M1 polarization of macrophages may play an central role in the pathogenesis of pSS.

The influence of a course of complex application of supravenous laser irradiation of blood and phototherapy on indicators of the neurohormonal status of patients with true eczema

BACKGROUND: In the pathogenesis of true eczema, an important place is occupied by stress, under the influence of which stimulation of the hypothalamus and brain stem occurs, as well as activation of the hypothalamic-pituitary-adrenal axis and the autonomic nervous system. Stress-induced secretion of neurotransmitters impairs the barrier function of the epidermis, slows wound healing, increases itching and inflammation, and suppresses immunity by changing the immune response of T-helper cells. AIM: Assessment of the severity of the corrective effect of a course of application of supravenous laser irradiation of blood and broadband medium-wave phototherapy on the blood levels of adrenocorticotropin, cortisol and beta-endorphin in patients with true eczema with a moderate form of the course. MATERIALS AND METHODS: The study was carried out with the participation of 120 patients with a moderate form of true eczema. Using simple fixed randomization, all patients were divided into 4 groups. The first group (control, n=30) received only basic drug therapy, including the use of detoxification, hyposensitizing, antihistamines and topical glucocorticosteroids. Patients of the second group (comparison group 1, n=30) additionally underwent a course of supravenous laser irradiation of blood. In the third group (comparison group 2, n=30), broadband medium-wave phototherapy was performed against the background of basic therapy. Patients of the fourth group (main group, n=30) in addition to basic therapy received a course of combined exposure to supravenous laser blood irradiation and phototherapy. The concentrations of adrenocorticotropin, cortisol and beta-endorphin were determined in the blood of patients twice (before the start of treatment and 1 month after the start of therapy) using ELISA. The clinical condition of patients in the groups was assessed by changes in the EASI index. Additionally, we studied the dynamics of the level of reactive and personal anxiety using the Spielberger–Khanin questionnaire. RESULTS: Positive dynamics of adrenocorticotropin, cortisol and beta-endorphin were noted only in the comparison groups and the main group, which proves the high efficiency of correction of the neurohumoral status of patients through a course of complex use of supravenous laser blood irradiation and broadband mid-wave phototherapy. Quantitative changes in the assessed parameters during complex therapy with therapeutic physical factors indicate a supra-additive version of their interaction, realized through different modalities, points of application and mechanisms for realizing the biological potential of physiotherapeutic effects. CONCLUSION: The results obtained convincingly prove the effectiveness of an additional course of use of supravenous laser irradiation of blood in combination with broadband medium-wave phototherapy when correcting the neuroendocrine status in patients with true eczema. The close correlation between neurohumoral indicators and clinical and psychological patterns of the disease proves the pathogenetic significance of the studied neuroendocrine indicators, which allows us to consider their dynamics as informative criteria for the effectiveness of the treatment.

Selenium and Arsenic Levels, Prevalence of Common Variants of Genes Involved in Their Metabolism, and Psoriasis Disease.

Using an Inductively Coupled Plasma Mass Spectrometer we measured the concentration of selenium and arsenic in serum and blood samples from 336 unselected psoriatic patients and 336 matched healthy controls to evaluate any associations with the clinical course of the disease. We genotyped 336 patients and 903 matched controls to evaluate the prevalence of SOD2 (rs4880), CAT (rs1001179), GPX1 (rs1050450), and DMGDH (rs921943) polymorphisms using Taqman assays. The mean selenium (Se) level in serum was 74 µg/L in patients and 86 µg/L in controls (p < 0.001). The mean Se level in blood was 95 µg/L in patients and 111 µg/L in controls (p < 0.001). Psoriasis risk was greatest among participants with the lowest serum (<68.75 µg/L, OR: 8.30; p < 0.001) and lowest blood concentrations of Se (<88.04 µg/L, OR: 10.3; p < 0.001). Similar results were observed in subgroups of males and females. We found an inverse correlation of selenium levels with PASI, NAPSI, and BSA scores. There was no significant difference in the distribution of the CAT, GPX1, DMGDH, and SOD2 polymorphisms. Among carriers of rs4880, rs1001179, and rs921943 polymorphisms, blood selenium levels were significantly lower. The mean arsenic level in serum was 0.79 µg/L in patients and 0.7 µg/L in controls (p = 0.2). The mean concentration in blood was 1.1 µg/L in patients and 1.3 µg/L in controls (p < 0.001). In conclusion, we found that lower selenium levels, in blood and serum, are associated with psoriasis risk and its more severe course. Future prospective studies should focus on the optimalisation of the concentration of this trace element not only for prophylactic guidance but also to support the treatment of this disease.

An AuNPs/Co3O4 nanocubic cage–based electrochemiluminescent immunosensor for Corin: A biomarker of stroke

Stroke, or cerebral apoplexy, is a paroxysmal disease that seriously threatens the neurological functions of middle-aged and older men, resulting in high rates of disability and mortality. The blood level of Corin can accurately predict the risk and subtype of stroke. Herein, an immunosensor was developed utilizing a nanocomposite of Au nanoparticles and Co3O4 nanocubic cages (AuNPs/Co3O4NcC) as the sensing substrate, with luminol serving as the sensing probe for Corin detection. Through the application of 3-aminopropyltrimethoxysilane, AuNPs/Co3O4NcC was affixed to the surface of indium tin oxide (ITO)-coated glass, considerably enhancing the electrochemiluminescence (ECL) performance of luminol due to its peroxidase-like activity. To confer biological specificity by immobilizing the Corin antibody on this substrate and to block residual active sites with bovine serum albumin, an immunosensor was developed. The capture of Corin protein by the antibody through an immune reaction, leading to its binding on the sensor, resulted in a decreased ECL signal. Under optimized conditions, the proposed ECL immunosensor demonstrated a broad linear response range from 1 pg/mL to 4800 pg/mL and a low detection limit of 0.26 pg/mL. This ECL immunosensor is characterized by its specificity, stability, and reproducibility and can detect Corin in real blood samples.

Elimination of Medium/High Molecular Weight Solutes. Comparison of High Flow Hemodialysis with Extended Hemodialysis

Introduction: Post-dilution online hemodiafiltration is the most efficient extracorporeal depurative treatment of CKD. Recently a new type of membrane has been developed, with a higher cut-off point also called a medium cut-off point, which has the capacity to eliminate higher molecular weight molecules in hemodialysis. The hemodialysis performed with these membranes has been called “Expanded Hemodialysis”. Objective: Compare the purifying efficacy of medium and high molecular weight molecules in patients dialyzed with high-flux hemodialysis, VitaPES 210HF, and with patients treated with expanded hemodialysis with the medium cut-off dialyzer, Elisio-HX. We also assessed the effect that the increased removal of inflammatory mediators by MCO hemodialysis had on fecal Calprotectin levels. Patients and methods: This is a prospective observational cross-over study in which 8 prevalent hemodialysis patients were followed for two months. Blood levels of IL-6, C-reactive protein (CRP), β2-microglobulin, Kappa and Lambda immunoglobulin light chains, and serum albumin were determined before and after each hemodialysis session. Results: The percentage of reduction of medium and higher molecular weight molecules: β2microglobulin, IL-6, Kappa and Lambda chains and CRP were higher with the Elisio-21HX dialyzer compared to the VitaPES 210HF dialyzer. There was no difference in albumin clearance between the two dialyzers. Fecal calprotectin levels were lower in patients dialyzed with Elisio-21HX. Conclusion: The medium cutoff dialyzer, Elisio-HX, is more efficient in the elimination of medium/high molecular weight molecules than the VitaPES HF high-flux dialyzer, with the same albumin elimination. Improving inflammation at the local intestinal level with lower levels of fecal Calprotectin.

Do heavy metals have a role in extrahepatic portal vein obstruction in children: A pilot case-control study

ObjectiveExtrahepatic portal venous obstruction (EHPVO) is a common cause of portal hypertension in Southeast Asia as compared to the western world, where chronic liver disease is the most common cause. Pollution and inadvertent exposure to heavy metals in poor socio-economic status in this part of the world are quite common. Therefore, this study was proposed to determine the association between heavy metal levels and oxidative stress in children with EHPVO. MethodsThis pilot case-control study was conducted in the department of Pediatrics, of a tertiary health care centre from January 2020 to October 2021. Children between 1 and 14 years, diagnosed with EHPVO were included. Controls were the healthy volunteers from OPD and near discharge indoor pediatrics patients. Metal analysis for Copper, Lead, Zinc, and Manganese, & Antioxidant activity for superoxide dismutase (SOD), Glutathione reductase (GR) and Lipid peroxidase (LPO) in form of malondialdehyde (MDA) was measured in both the groups. ResultsA total of 80 subjects were enrolled (40 EHPVO cases and 40 controls) mean age for cases was 8.15 ± 3.53, and for control, was 7.69 ± 3.55 years (p = 0.560). Lead values were found to be significantly higher (p = 0.003) in EHPVO cases (5.39 ± 3.13) in comparison to controls (3.30 ± 2.91). Mean superoxide dismutase (SOD) and Glutathione reductase (GR) values were decreased (p = 0.035- GR) and the malondialdehyde (MDA) value was increased in the EHPVO cases as compared to controls. ConclusionChildren with high blood levels of lead might be at risk of portal vein thrombosis resulting in EHPVO, and lead-induced oxidative stress.

Non-HLA angiotensin-type-1 receptor autoantibodies mediate the long-term loss of grafted neurons in Parkinson’s disease models

BackgroundClinical trials have provided evidence that transplants of dopaminergic precursors, which may be replaced by new in vitro stem cell sources, can integrate into the host tissue, and alleviate motor symptoms in Parkinson´s disease (PD). In some patients, deterioration of graft function occurred several months after observing a graft-derived functional improvement. Rejection of peripheral organs was initially related to HLA-specific antibodies. However, the role of non-HLA antibodies is now considered also relevant for rejection. Angiotensin-II type-1 receptor autoantibodies (AT1-AA) act as agonists of the AT1 receptors. AT1-AA are the non-HLA antibodies most widely associated with graft dysfunction or rejection after transplantation of different solid organs and hematopoietic stem cells. However, it is not known about the presence and possible functional effects of AT1-AA in dopaminergic grafts, and the effects of treatment with AT1 receptor blockers (ARBs) such as candesartan on graft survival.MethodsIn a 6-hydroxydopamine PD rat model, we studied the short-term (10 days)- and long-term (3 months) effects of chronic treatment with the ARB candesartan on survival of grafted dopaminergic neurons and microglial graft infiltration, as well as the effects of dopaminergic denervation and grafting on serum and CSF AT1-AA levels. The expression of AT1 receptors in grafted neurons was determined by laser capture microdissection.ResultsAt the early period post-grafting, the number of grafted dopaminergic neurons that survived was not significantly different between treated and untreated hosts (i.e., control rats and rats treated with candesartan), probably because, just after grafting, other deleterious factors are predominant for dopaminergic cell death, such as mechanical trauma, lack of growth factors/nutrients and ischemia. However, several months post-grafting, we observed a significantly higher number of surviving dopaminergic neurons and a higher density of striatal dopaminergic terminals in the candesartan-treated group. For several months, grafted rats showed blood and cerebrospinal fluid levels of AT1-AA higher than normal controls, and also higher AT1-AA levels than non-grafted parkinsonian rats.ConclusionsThe results suggest the use of ARBs such as candesartan in PD patients, particularly before and after dopaminergic grafts, and the need to monitor AT1-AA levels in PD patients, particularly in those candidates for dopaminergic grafting.

Diagnostic efficacy of [68Ga]Ga-DOTA-GPFAPI-04 in patients with solid tumors in a head-to-head comparison with [18F]F-FDG: results from a prospective clinical study.

To identify the biodistribution and diagnostic performance of a novel fibroblast activation protein (FAP) targeted positron emission tomography (PET) tracer, [68Ga]Ga-DOTA-GPFAPI-04, in patients with solid tumors in a head-to-head comparison with [18F]F-FDG. Twenty-six patients histologically proven with cancers of nasopharyngeal (n = 5), esophagus (n = 5), gastro-esophagus (n = 1), stomach (n = 7), liver (n = 3), and colorectum (n = 5) were recruited for [68Ga]Ga-DOTA-GPFAPI-04 and [18F]F-FDG PET/CT scans on consecutive days. The primary endpoint was the diagnostic efficacy, with the histological diagnosis and the follow-up results selected as the gold standard. The secondary endpoint was the background uptake pattern. Two experienced nuclear medicine physicians who were blinded to the gold standard results while having essential awareness of the clinical context reviewed the images and labeled lesions by consensus for subsequent software-assisted lesion segmentation. Additionally, background organs were automatically segmented, assisted by artificial intelligence. Volume, mean, and maximum standard uptake values (SUVmean and SUVmax) of all segmentations were recorded. P < 0.05 was deemed as statistically significant. Significant glandular uptake of [68Ga]Ga-DOTA-GPFAPI-04 was detected in the thyroid, pancreas, and submandibular glands, while moderate uptake was observed in the parotid glands. The myocardium and myometrium exhibited 2-3 times higher uptake of the radiotracer than that of the background levels in blood and liver. A total of 349 targeted lesions, consisting of 324 malignancies and 25 benign lesions, were segmented. [68Ga]Ga-DOTA-GPFAPI-04 is more sensitive than [18F]F-FDG, especially for abdominopelvic dissemination (1.000 vs. 0.475, P < 0.001). Interestingly, [18F]F-FDG demonstrated higher sensitivity for lung metastasis compared to [68Ga]Ga-DOTA-GPFAPI-04 (0.845 vs. 0.682, P = 0.003). The high glandular uptake made it difficult to delineate lesions in close proximity and masked two metastatic lesions in these organs. Despite prominent glandular uptake, [68Ga]Ga-DOTA-GPFAPI-04 demonstrates favorable diagnostic performance. It is a promising probe scaffold for further development of FAP-targeted tumor theranostic agents.

Pharmacodynamic monitoring by residual gene expression of the nuclear factor of activated T cell-regulated genes in lung transplant recipients and its correlation with tacrolimus blood levels.

Trough blood levels (C0) of tacrolimus are used to adjust drug dosage, but they do not consistently correlate with clinical outcomes. Measurement of residual gene expression of nuclear factor of activated T cell (NFAT)-regulated genes (NFAT-RGE) has been proposed as a pharmacodynamic biomarker to assess the degree of immunosuppression in certain solid organ transplantations, but little is known regarding lung transplant recipients (LTR). Our primary objective is to correlate tacrolimus blood levels with NFAT-RGE. NFAT-RGE and tacrolimus C0 and peak (C1.5) levels were determined in 42 patients at three, six and 12 months post-transplantation. Tacrolimus C0 did not exhibit a correlation with NFAT-RGE, whereas C1.5 did. Besides, over 20% of measurements indicated high levels of immunosuppression based on the below 30% NFAT-RGE threshold observed in many studies. Among those measurements within the therapeutic range, 19% had an NFAT-RGE<30%. Consequently, a subset of patients within the tacrolimus therapeutic range may be more susceptible to infection or cancer, potentially benefiting from NFAT-RGE and tacrolimus peak level monitoring to tailor their dosage. Further quantitative risk assessment studies are needed to elucidate the relationship between NFAT-RGE and the risk of infection, cancer, or rejection.

Associations among neighborhood walkability, metal exposure, and sex steroid hormone levels: Results from Hangzhou Birth Cohort Study Ⅱ

BackgroundNeighborhood walkability may influence maternal-fetal exposure to environmental hazards and maternal-fetal health (e.g., fetal growth restriction, reproductive toxicity). However, few studies have explored the association between neighborhood walkability and hormones in pregnant women. MethodsWe included 533 pregnant women from the Hangzhou Birth Cohort Study II (HBCS-II) with testosterone (TTE) and estradiol (E2) measured for analysis. Neighborhood walkability was evaluated by calculating a walkability index based on geo-coded addresses. Placental metals were measured using inductively coupled plasma mass spectrometry (ICP-MS). TTE and E2 levels in umbilical cord blood were measured using chemiluminescence microparticle immunoassay (CMIA). Linear regression model was used to estimate the relationship between the walkability index, placental metals, and sex steroid hormones. Effect modification was also assessed to estimate the effect of placental metals on the associations of neighborhood walkability with TTE and E2. ResultsNeighborhood walkability was significantly linked to increased E2 levels (P trend=0.023). Compared with participants at the first quintile (Q1) of walkability index, those at the third quintiles (Q3) had lower chromium (Cr) levels (β = −0.212, 95% CI = −0.421 to −0.003). Arsenic (As), cobalt (Co), manganese (Mn), molybdenum (Mo), nickel (Ni), lead (Pb), antimony (Sb), selenium (Se), tin (Sn), and vanadium (V) were linked to decreased TTE levels, and cadmium (Cd) was linked to increased TTE levels. No metal was significantly associated with E2 levels in trend analysis. In the analysis of effect modification, the associations of neighborhood walkability with TTE and E2 were significantly modified by Mn (P = 0.005) and Cu (P = 0.049) respectively. ConclusionNeighborhood walkability could be a favorable factor for E2 production during pregnancy, which may be inhibited by maternal exposure to heavy metals.

Discrepant Phenotyping of Monocytes Based on CX3CR1 and CCR2 Using Fluorescent Reporters and Antibodies.

Monocytes, as well as downstream macrophages and dendritic cells, are essential players in the immune system, fulfilling key roles in homeostasis as well as in inflammatory conditions. Conventionally, driven by studies on reporter models, mouse monocytes are categorized into a classical and a non-classical subset based on their inversely correlated surface expression of Ly6C/CCR2 and CX3CR1. Here, we aimed to challenge this concept by antibody staining and reporter mouse models. Therefore, we took advantage of Cx3cr1GFP and Ccr2RFP reporter mice, in which the respective gene was replaced by a fluorescent reporter protein gene. We analyzed the expression of CX3CR1 and CCR2 by flow cytometry using several validated fluorochrome-coupled antibodies and compared them with the reporter gene signal in these reporter mouse strains. Although we were able to validate the specificity of the fluorochrome-coupled flow cytometry antibodies, mouse Ly6Chigh classical and Ly6Clow non-classical monocytes showed no differences in CX3CR1 expression levels in the peripheral blood and spleen when stained with these antibodies. On the contrary, in Cx3cr1GFP reporter mice, we were able to reproduce the inverse correlation of the CX3CR1 reporter gene signal and Ly6C surface expression. Furthermore, differential CCR2 surface expression correlating with the expression of Ly6C was observed by antibody staining, but not in Ccr2RFP reporter mice. In conclusion, our data suggest that phenotyping strategies for mouse monocyte subsets should be carefully selected. In accordance with the literature, the suitability of CX3CR1 antibody staining is limited, whereas for CCR2, caution should be applied when using reporter mice.

Chronic Lead Exposure Impairment of Hypothalamic-Pituitary-Gonadal Axis in Adult Male Wistar Rats: Biochemical and Histomorphological Evidence

Introduction: The upsurge in male infertility has been associated with impaired hypothalamic-pituitary-gonadal (HPG) axis. There is a dearth of conclusive empirical data as to the deleterious impacts of heavy metal intoxication on male reproductive functioning through the HPG axis. Objective: This study seeks to elucidate the possible effects of chronic lead exposure on HPG signalling activities via biochemical and histopathological assessment. Experimental Section/Material and Methods: Forty adult male Wistar rats were randomised into four experimental groups (n=10). Group A, the control group received standard feed and water ad libitume. In Groups B, C and D, animals were orally administered lead acetate at concentrations of 2.5% 3.0% and 3.5%, respectively, using a stock solution of 150mg/kg once daily for 35 days. After the treatment period, all animals were fasted overnight and euthanized by cervical dislocation. Blood levels of anterior pituitary hormones (FSH and LH) were analysed using standard methods. Statistical analyses was done on graph pad prism. Testicular tissue was processed routinely for histopathological analyses using different stains. Results: Hormonal assays showed no significant changes in follicle-stimulating hormone (FSH) and luteinizing hormone (LH) (p&gt;0.05) levels across groups. However, histological examination revealed alterations in testicular architecture, including disrupted spermatogonia cell arrangement and reduced Sertoli cell numbers, indicative of adverse effects on spermatogenesis. Conclusion: Chronic lead exposure adversely affects testicular histomorphology in adult male Wistar rats, potentially impacting reproductive function. While hormonal levels remain relatively unaffected, alterations in testicular structure suggest a direct impact on gonadal functions at a cellular level.

Nano Encapsulation of An Essential Oil Transpire the Therapeutic Approach.

Essential oils are natural compounds extracted from plants that are volatile and sensitive to heat. Due to their therapeutic value, essential oils are now used in many industries, including the sanitary, cosmetic, agricultural, food, and pharmaceutical industries. These are complex mixtures of a wide range of volatile molecules, including phenol-derived aliphatic and aromatic compounds and terpenoids. Essential oils have been used medicinally since ancient times for their antibacterial, antifungal, antiviral, antiparasitic, insecticidal, sedative, antiinflammatory, and anaesthetic properties. However, essential oils come with inherent limitations; thus, nanoencapsulation is advocated as a remedy as it has the potential to enhance the stability, solubility, and effectiveness of formulations based on essential oils, all while preserving the therapeutic drug blood levels. It is not always viable to use essential oils independently in treatment due to several restrictions; however, nanodelivery technologies appear capable of overcoming these challenges. The therapeutic efficacy that is achieved can be affected by several factors, including the selection of the essential oil as well as the system of nanodelivery. Today, nanoencapsulation is capable of enabling the simultaneous delivery of multiple oils, providing synergistic effects, and facilitating the development of combinational therapies. Additionally, they may have potential applications in preserving food to prolong the shelf life of quickspoiling items and their fragrances. While there is already much research on the characterisation of EOs, this review evaluates the features of the nanoparticles employed for the delivery of essential oils and their impact on the functionality of nano-delivered essential oils and their beneficial uses.

The Effect of Coffee Consumption on the Level of Adrenalin Blood Serum in the Periodontitis Model: An In Vivo Study

Background: Adrenalin was supposed to have an anti-inflammatory effect; hence adrenalin concentration in blood serum might be lower in inflammatory diseases. Coffee contains caffeine that is thought to have the potency to increase adrenalin secretion in inflammatory diseases. This study aimed to analyze the effect of coffee consumption on adrenalin blood levels in periodontitis rat model. Methods: This in vivo experimental study used the post-test-only control group design. Wistar male rats (Rattus novergicus) were divided into four groups (four rats/group) i.e. 1) Periodontitis (no coffee), 2) periodontitis + coffee, 3) Coffee (no periodontitis), 4) Control (no coffee, no periodontitis). The periodontitis rat model was made by injecting periodontitis bacteria Phorpyromonas gingivalis in the buccal mucosa of the lower molar tooth three times a week for 4 weeks. A single dose (0.6 mL d–1) of ground coffee infusion (equal to one cup per day for humans) was given to each rat in the coffee group, for 28 d. At the end of the study, all of the rats were sacrificed and blood was drawn intra-cardially. Blood serum adrenalin concentration was analyzed using Enzyme-linked immunosorbent assay (Elisa). Results: The Periodontitis group showed significantly lower serum adrenalin (p&lt; 0.05) than others. Coffee consumption in periodontitis rats affected a significantly higher adrenalin blood serum level (p &lt; 0.05). Conclusion: Coffee consumption could replenish the level of blood serum adrenalin which decreases in periodontitis. Further studies are needed to elucidate the modulation mechanism of coffee-adrenalin-inflammation.

High nitrate levels in skeletal muscle contribute to nitric oxide generation via a nitrate/nitrite reductive pathway in mice that lack the nNOS enzyme.

Nitric oxide (NO) is a vasodilator gas that plays a critical role in mitochondrial respiration and skeletal muscle function. NO is endogenously generated by NO synthases: neuronal NO synthase (nNOS), endothelial NO synthase (eNOS), or inducible NO synthase (iNOS). NO in skeletal muscle is partly generated by nNOS, and nNOS deficiency can contribute to muscular dystrophic diseases. However, we and others discovered an alternative nitrate/nitrite reductive pathway for NO generation: nitrate to nitrite to NO. We hypothesized that nitrate supplementation would increase nitrate accumulation in skeletal muscle and promote a nitrate/nitrite reductive pathway for NO production to compensate for the loss of nNOS in skeletal muscle. Wild-type (WT) and genetic nNOS knockout (nNOS-/-) mice were fed normal chow (386.9nmol/g nitrate) and subjected to three treatments: high-nitrate water (1g/L sodium nitrate for 7days), low-nitrate diet (46.8nmol/g nitrate for 7days), and low-nitrate diet followed by high-nitrate water for 7days each. High-nitrate water supplementation exhibited a greater and more significant increase in nitrate levels in skeletal muscle and blood in nNOS-/- mice than in WT mice. A low-nitrate diet decreased blood nitrate and nitrite levels in both WT and nNOS-/- mice. WT and nNOS-/- mice, treated with low-nitrate diet, followed by high-nitrate water supplementation, showed a significant increase in nitrate levels in skeletal muscle and blood, analogous to the increases observed in nNOS-/- mice supplemented with high-nitrate water. In skeletal muscle of nNOS-/- mice on high-nitrate water supplementation, on low-nitrate diet, and in low-high nitrate treatment, the loss of nNOS resulted in a corresponding increase in the expression of nitrate/nitrite reductive pathway-associated nitrate transporters [sialin and chloride channel 1 (CLC1)] and nitrate/nitrite reductase [xanthine oxidoreductase (XOR)] but did not show a compensatory increase in iNOS or eNOS protein and eNOS activation activity [p-eNOS (Ser1177)]. These findings suggest that a greater increase in nitrate levels in skeletal muscle of nNOS-/- mice on nitrate supplementation results from reductive processes to increase NO production with the loss of nNOS in skeletal muscle.

Decreased circulating IPA levels identify subjects with metabolic comorbidities: A multi-omics study

In recent years several experimental observations demonstrated that the gut microbiome plays a role in regulating positively or negatively metabolic homeostasis. Indole-3-propionic acid (IPA), a Tryptophan catabolic product mainly produced by C. Sporogenes, has been recently shown to exert either favorable or unfavorable effects in the context of metabolic and cardiovascular diseases. We performed a study to delineate clinical and multiomics characteristics of human subjects characterized by low and high IPA levels. Subjects with low IPA blood levels showed insulin resistance, overweight, low-grade inflammation, and features of metabolic syndrome compared to those with high IPA. Metabolomics analysis revealed that IPA was negatively correlated with leucine, isoleucine, and valine metabolism. Transcriptomics analysis in colon tissue revealed the enrichment of several signaling, regulatory, and metabolic processes. Metagenomics revealed several OTU of ruminococcus, alistipes, blautia, butyrivibrio and akkermansia were significantly enriched in highIPA group while in lowIPA group Escherichia-Shigella, megasphera, and Desulfovibrio genus were more abundant.Next, we tested the hypothesis that treatment with IPA in a mouse model may recapitulate the observations of human subjects, at least in part. We found that a short treatment with IPA (4 days at 20/mg/kg) improved glucose tolerance and Akt phosphorylation in the skeletal muscle level, while regulating blood BCAA levels and gene expression in colon tissue, all consistent with results observed in human subjects stratified for IPA levels. Our results suggest that treatment with IPA may be considered a potential strategy to improve insulin resistance in subjects with dysbiosis.

Combined hypolipidemic therapy with rosuvastatin and ezetimibe is the key to success in the treatment and prevention of cardiovascular diseases

Combined hypolipidemic therapy with rosuvastatin and ezetimibe is the key to success in the treatment and prevention of cardiovascular diseases