High Blood Levels Research Articles

Association between trandsferrin receptor and urine cobalt: NHANES 2015-2020

Abstract. The transferrin receptor protein 1 (TfR1) is a critical cellular membrane protein. It orchestrates the internal transport and metabolism of iron, a vital process for intracellular functions. Additionally, TfR1 has the capacity to bind with metals beyond iron, including cobalt and manganese; however, the specific mechanisms of this binding and subsequent interactions with other proteins remain elusive. This study delves into the potential correlation between TfR1 levels in humans and the presence of cobalt in urine. Drawing on data from 3,424 participants across three survey cycles spanning two years each, this paper meticulously contrasts the clinical features of individuals across diverse TfR1 and urinary cobalt levels. Through the lens of both univariate and multivariate linear regression analyses, the research uncovers an inverse connection between TfR1 concentrations and urinary cobalt, post exclusion of participants with incomplete biochemical profiles. This inverse relationship could shed light on the complex interplay between TfR1 and metal ions within the body, providing a deeper understanding that may inform future studies and potential clinical applications. In the multivariate linear regression analysis, it is found that with the increasing of TFR1 quartiles, the proportion of obese participants (P<0.01), high level blood manganese, high cobalt level in urine and blood (P<0.01) increased gradually. This association remained significant in sensitivity analysis, while in the stratified analysis, above association was not significant in men with samples aged 65 and over. Transferrin receptor protein levels might be positively associated with urinary cobalt in the general U.S. crowd.

Clinical and diagnostic evidence of benign endometrial pathology in postmenopausal patients

The objective: to study clinical and diagnostic features of the benign endometrial conditions in the postmenopausal women.Materials and method. 64 postmenopausal patients with various severity of postmenopausal vaginal bleeding were examined. All patients underwent clinical, radiological, laboratory and histological examinations, reproductive history data and body mass index indicators were evaluated. Of them 33 persons were diagnosed with complex endometrial hyperplasia without atypia, 16 women – endometrial polyp and 15 women – hyperplasia with atypia. Routine gynecological examination including abdominal and pelvic examination following transvaginal ultrasound examination for the determination of the uterine and ovarian volume as well, as the endometrial thickness were conducted. Patients included in the study underwent computer tomography and magnetic resonance imaging as indicated. All patients with endometrial pathology underwent endometrial biopsy by standard dilatation and curettage or Pipelle-biopsy with histological examination of the obtained material. The concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH), dehydroepiandrosterone sulfate (DHEA-S), estradiol, estrone, progesterone, prolactin, and testosterone were determined in blood serum.Results. It was confirmed that in 87,5% of cases endometrial hyperplasia manifested with vaginal bleeding. Endometrial thickness in examined persons ranged from 14.1±1.6 mm in patients with atypical endometrial hyperplasia to 21.3±4.8 mm in patients with complex endometrial hyperplasia without atypia. The study of blood levels of hormones found that postmenopausal patients with endometrial hyperplasia have lower FSH concentration, LH/FSH ratio, estradiol, testosterone levels, with significantly high values of prolactin, DHEA-S and estrone. During the postmenopausal period, hyperplasia was developed in 10% of cases by the presence of bleeding, and 86.2% of cases by the presence of blood spotting. Conclusions. The study suggests that high body mass index, numerous artificial abortions, high blood levels of estrone, DHEA-S and prolactin as well as increased thickness of endometrium influence the frequency of endometrial hyperplasia in postmenopausal women.

Mirtazapine blood levels and antidepressant response

Objective Therapeutic drug monitoring (TDM) is an important tool for treatment optimisation. Its usefulness has recently been demonstrated for some first-line antidepressants; however, few studies have been reported on the relationship between blood levels of mirtazapine and its antidepressant effects. The aim of this study was to investigate the association between blood concentration of mirtazapine and antidepressant response. Methods 59 outpatients treated with mirtazapine for depression were recruited and followed up for three months in a naturalistic setting. Hamilton Depression Rating Scale-21 (HAMD-21) was administered at baseline, month 1, and month 3 to assess antidepressant response. Mirtazapine serum concentration was measured at steady state. Linear regression analysis and nonlinear least-squares regression were used to estimate association between serum concentration of mirtazapine and antidepressant response. Results Our results showed no overall association between serum concentration of mirtazapine and symptom improvement at month 1 and month 3. A marginally significantly higher serum concentration of mirtazapine was found in responders vs non-responders at month 3. Conclusions The study suggests that serum concentration of mirtazapine is not strongly associated with the antidepressant efficacy of mirtazapine. This is probably attributed to its pharmacodynamic profile, even though higher blood levels seem to be marginally more effective.

Synthesis and Structure-Activity Relationship Analysis of 2-Substituted-1,2,4-Triazolo[1,5-a]Pyrimidin-7-Ones and their 6-Carboxylate Derivatives as Xanthine Oxidase Inhibitors.

Hyperuricemia is characterised by high blood levels of uric acid, and it can degenerate into gout when monosodium urate crystals precipitate in joints and other tissues. Uric acid is produced during the catabolism of xanthine by the enzyme xanthine oxidase (XO), which is the primary therapeutic target in gout treatment. Current XO inhibitors approved to treat gout, such as allopurinol and febuxostat, suffer from serious adverse effects, creating the need for new drug molecules. Three libraries comprising 75 purine analogues were designed using a 1,2,4-triazolo[1,5-a]pyrimidine scaffold, synthesised and tested in vitro as potential XO inhibitors. The screening identified that 23 compounds exhibited better inhibitory activity than allopurinol, with 2-(4-isopropoxyphenyl)-7-oxo-4,7-dihydro-1,2,4-triazolo[1,5-a]pyrimidine-6-carboxylic acid being 23 times more potent. Enzyme kinetics studies and molecular docking simulations were performed on the most active compounds to identify the mechanism of action and intermolecular interactions between the active site of XO and the inhibitors. The most potent compounds exhibited a mix-type inhibition mechanism and were predicted to interact with the same amino acid residues as allopurinol. These novel purine analogues are promising hits for further new lead development among purine-like drug XO inhibitors with therapeutic potential in the treatment of hyperuricemia and associated diseases.

Immune Biomarkers at Birth Predict Lower Respiratory Tract Infection Risk in a Large Birth Cohort.

Lower respiratory tract infections (LRTIs) remain the leading cause of infant morbidity and mortality worldwide and affect long-term respiratory health. Identifying immunological determinants of LRTI susceptibility may help stratify disease risk and identify therapies. This study aimed to identify neonatal immunological factors predicting LRTI risk in infancy. Cord blood plasma from 191 neonates from the Boston Birth Cohort was analyzed for 28 soluble immune factors. LRTI was defined as bronchiolitis, bronchitis, or pneumonia during the first year of life. Welch's t-test demonstrated significantly higher log10 transformed concentrations of IL-17 and IFNγ in the LRTI group compared to neonates without LRTI in the first year of life (p < 0.05). Risk associations were determined using multivariate survival models. There were 29 infants with LRTIs. High cord blood levels of IFNγ (aHR = 2.35, 95% CI 1.07-5.17), TNF-β (aHR = 2.86, 95% CI 1.27-6.47), MIP-1α (aHR = 2.82, 95% CI 1.22-6.51), and MIP-1β (aHR = 2.34, 95% CI 1.05-5.20) were associated with a higher risk of LRTIs. RANTES was associated with a lower risk (aHR = 0.43, 95% CI 0.19-0.97). Soluble immune factors linked to antiviral immunity (IFNγ) and cytokines mediating inflammatory responses (TNF-β), and cell homing (MIP-1α/b), at birth were associated with an increased risk of LRTIs during infancy.

The Number of Episodes of Subtherapeutic Tacrolimus Blood Level Is Independently Associated With Reduced Kidney Graft Survival

ABSTRACTBackgroundTacrolimus blood level variability is associated with reduced graft survival among kidney transplant recipients. To date, no practical approach for reducing variability has been validated. We defined specific tacrolimus blood level patterns correlated with variability and evaluated their independent association with reduced graft survival.MethodsIn this single‐center retrospective study, we predefined 12 patterns that exhibited correlation with high tacrolimus blood level variability. Subsequently, we utilized a multivariate Cox proportional hazard model, in conjunction with the Akaike information criteria, to evaluate the association between the predefined patterns and decreased graft survival.ResultsOur cohort included 1305 kidney transplant recipients. The primary outcome of this trial was graft loss, defined as the initiation of chronic dialysis or the need for retransplantation. The secondary outcome was the combination of death‐censored graft loss and death with a functioning graft. During the study's follow‐up period, there were 131 events of graft loss. The number of episodes of subtherapeutic tacrolimus level during the first‐year posttransplantation was significantly associated with graft loss (HR 1.208 per episode, 95% CI 1.075–1.356, p = 0.001) and significantly improved the relative likelihood of the model compared to the multivariate model as demonstrated by the delta AIC value (8.256, p = 0.016).ConclusionIn addition to increased tacrolimus blood level variability, the number of episodes of subtherapeutic tacrolimus levels is independently associated with decreased graft survival among kidney transplant recipients.

Analysis of data from the Russian AURA registry (real-world data registry on AlbUminuRia detection rate among patients with previously undiAgnosed chronic kidney disease)

Aim. To present data from the AURA Registry (real-world data registry on AlbUminuRia detection rate among patients with previously undiAgnosed chronic kidney disease). It is important to perform population studies both to study the occurrence of markers (albuminuria (AU), decreased glomerular filtration rate (GFR)) and the prevalence of chronic kidney disease (CKD), which will provide information on the actual detection rate of CKD and the related markers in territories included in the registry of research centers.Material and methods. The article presents the first data from the AURA registry. Recruitment was carried out from March 6, 2023 to January 23, 2024. Thirty-four research centers in various federal districts of the Russian Federation and 104 doctors took part in the recruitment. We included 4580 subjects over the age of 40 years who had no previously established diagnosis of CKD and did not have type 1 or type 2 diabetes. During recruitment, the researchers were guided by the AURA study protocol (Version 1.7/12-26-2022).Results. AU more than 20 mg/g was detected in 64,9% of cases. At the same time, AU is more common at GFR values that may correspond to stage 3A of CKD. The rarer occurrence of AU in those examined with GFR &gt;60 ml/min/1,73 m2 may be explained by less severe renal damage at this CKD stage. The incidence of AU was significantly higher in men, older people, smokers, people with metabolic syndrome, hypertension (HTN), prediabetes and overweight. The occurrence of AU also increased as HTN grade increased. AU detection rate was associated with hypertriglyceridemia, a high blood level of C-reactive protein, which is an integrative marker of inflammation that negatively affects cardiovascular risk.Conclusion. The presented first data from the AURA registry demonstrated the high AU prevalence in people over 40 years of age. A high incidence of AU was typical for patients with HTN, coronary artery disease, atrial fibrillation, heart failure, and prediabetes. An association has been demonstrated between the high incidence of AU and male sex, age, overweight, hyperuricemia, dyslipidemia, and a number of other cardiovascular risk factors.

Elevated Heavy Metal(loid) Blood and Feather Concentrations in Wetland Birds from Different Trophic Levels Indicate Exposure to Environmental Pollutants

The research assessed the exposure to total mercury (THg), lead (Pb), and arsenic (As) in Colombian wetland species of different trophic levels Platalea ajaja, Dendrocygna autumnalis and Nannopterum brasilianus. The results show high THg blood levels in P. ajaja (811.00 ± 349.60 µg L–1) and N. brasilianus (209.50 ± 27.92 µg L–1) with P. ajaja possibly exhibiting adverse effects. Blood Pb concentration was high in D. autumnalis (212.00 ± 208.10 µg L–1) and above the threshold for adverse effects, suggesting subclinical poisoning. Levels of blood As were below the assumed threshold for detrimental effect (20 μg L−1). The mean concentration of feather THg was below the assumed natural background levels (5 µg g−1) for all three species. Feather Pb levels exceeded the levels for assumed threshold effects in all sampled N. brasilianus (7.40 ± 0.51 µg g–1). Results for feather As concentration were below the threshold for adverse impacts in all species, although a positive correlation between As and THg concentrations was detected in P. ajaja feathers. The overall results could help understand how metal(loid)s biomagnify through trophic levels and how wetland species may serve as environmental indicators. By exploring the interactions of metal(loid)s within different matrices and body, this study offers insights into the dynamics of contaminant accumulation and distribution in the environment. This concept can be applied to wetlands worldwide, where bird species can serve as indicators of ecosystem health and the presence of contaminants such as heavy metals and metalloids.

Heavy metals are liver fibrosis risk factors in people without traditional liver disease etiologies

Liver fibrosis is an important predictor of mortality. Liver disease case definitions changed in 2023. These definitions include an easily over-looked group with no traditional etiology (NTE) of liver disease and no steatosis. We analyzed heavy metals and cardiometabolic risk factors (CMRFs) as fibrosis risk factors in the NTE group and in people with another newly-defined condition, metabolic dysfunction-associated steatotic liver disease (MASLD). Two National Health and Nutrition Examination Survey (NHANES) datasets were analyzed. In NHANES III (1988–1994), fibrosis and steatosis were defined by Fibrosis-4 scores and ultrasound, respectively, in 12,208 adults. In NHANES 2017–2020, fibrosis and steatosis were defined by transient elastography and the controlled attenuation parameter (CAP) in 5525 adults. Fibrosis risk factors varied over time and by race/ethnicity. In the earlier dataset, NTE-fibrosis had a positive, non-significant, association with high blood levels of lead (Pb). MASLD-fibrosis was associated with Pb (OR = 2.5, 95 % CI, 1.4–4.4) and not with CMRFs in non-Hispanic Blacks but was associated with CMRFs in non-Hispanic Whites. Heavy metal exposures fell between the two time periods. In the later dataset, NTE-fibrosis was associated with Pb (OR = 4.2, 95 % CI, 2.6–6.8) and cadmium (OR = 1.8, 95 % CI, 1.1–3.0) in the total population, but not with CMRFs. MASLD-fibrosis was strongly-significantly associated with CMRFs in every racial/ethnic group except non-Hispanic Blacks in whom CMRFs were only weakly associated with MASLD-fibrosis. Heavy metal pollution, which disproportionately impacts minoritized populations, decreased over time, but remained strongly associated with liver fibrosis in people lacking traditional etiological factors for liver disease.

Evaluation of Lead and Cadmium Levels in Individuals Exposed to Cement Dust

Background: Heavy metals such as lead and cadmium, which are present in cement dust, are elements with a density of more than 5 g/cm3 that are harmful to both the environment and living creatures. This study was set out to evaluate levels of lead and cadmium in individuals exposed to cement dust in Nnewi metropolis. Study Design: This case-control study was carried out among male and female workers in cement depots in Nnewi metropolis who were selected by simple random sampling. Methods: Thirty-five individuals exposed to cement dust defined as test participants and thirty-five individuals not exposed to cement dust defined as control participants within the age range of 18 and 51 years were selected into this study. Test participants were sub-grouped based on years of exposure to cement dust into 3 years and below, 4 to 6 years and 7 years and above. Five millilitres of whole blood was collected from each selected participant and levels of lead and cadmium were determined using atomic absorption spectrometry. Data were analysed using Independent Student’s T-test and ANOVA with least significant difference post hoc. Data was presented as mean ± standard deviation and significance level was taken at p&lt; 0.05. Results: The blood levels of lead and cadmium in test participants were significantly higher than blood levels in control participants. The lead levels were significantly higher in test participants exposed to cement dust for 7 years and above than in test participants exposed to cement dust between 4 to 6 years and test participants exposed to cement dust for 3 years and below (p&lt;0.001). There was no significant difference in serum levels of cadmium between test participants exposed to cement dust for 3 years and below, test participants exposed to cement dust between 4 years to 6 years and test participants exposed to cement dust for 7 years and above (p&gt;0.05). Conclusion: Occupational exposure to cement dust causes high blood levels of lead and cadmium in the body and this accumulation is dangerous to health.

Exposure to toxic chemical elements among people living with HIV/AIDS in Northern Tanzania

Environmental exposure to toxic chemicals including cadmium (Cd), lead (Pb), and mercury (Hg), are known risk factors for cardiovascular (CVD) and kidney disease. In people living with HIV (PLWH), CVD and kidney disease are the leading cause of death. Neither traditional risk factors nor markers of HIV infection fully explain such an increased risk. It is of paramount importance to establish the epidemiology of toxic chemicals exposure in PLWH, to inform screening and prevention interventions in this vulnerable population. This cross-sectional study compares toxic chemical levels (T-Cd, T-Pb, and T-Hg) among PLWH and HIV-uninfected adults in Northwestern Tanzania. A total of 495 PLWH and 505 HIV-uninfected subjects were analyzed. Spearman's rank correlations were used to examine the relationship between toxic chemical elements by HIV status. Linear regression models were used to determine the association between exposures and outcomes of interest among study participants. In both PLWH and HIV-uninfected adults, blood T-Cd, T-Pb, and T-Hg levels were frequently found at levels above the reference value of 5, 50, and 20 μg/L, respectively. Overall, factors associated with blood toxic chemical levels included vegetable servings per week, obesity, untreated water sources, use of alcohol, and HIV. Among PLWH, weekly vegetable intake provided a protective effect against T-Cd (Coeff = −0.03, 95%CI = −0.06, −0.01) and T-Pb (Coeff = −0.05, 95%CI = −0.09, −0.01) exposure among PLWH. Alcohol intake (Coeff = 0.10, 95%CI = 0.06, 0.13), obesity (Coeff = 0.08, 95%CI = 0.02, 0.13), longer duration to indoor smoke exposure (Coeff = 0.003, 95%CI = 0.001, 0.004), and HIV infection (Coeff = 0.11, 95%CI = 0.07, 0.15) were associated with increased individuals blood T-Hg levels. Individuals in northwestern Tanzania, including PLWH, have high blood levels for T-Cd, T-Pb, and T-Hg. Factors associated with higher blood levels include water sources, obesity, use of alcohol, exposure to indoor smoke, and HIV infection.

ASSOCIATION OF HAEMATOLOGICAL INFLAMMATORY PARAMETERS WITH MISCARRIAGES

Purpose: We aimed to find out whether the systemic immune inflammatory index and the pan-immune inflammatory score can be used as markers for predicting continuation of pregnancy in the prediction of threatened abortion. Materials and Method: This case-control study was conducted retrospectively in the Obstetrics and Gynaecology Clinic of Ankara Etlik City Hospital. Patients who were admitted to our hospital due to bleeding or pain and were hospitalised with a diagnosis of abortus imminens or were treated as outpatients were divided into two groups. The indices derived from the haemogram results were compared between the patients whose pregnancy did not result in miscarriage (Group I) and those whose pregnancy resulted in miscarriage (Group II), and the performance of the indices in predicting the continuation of pregnancy was evaluated. Results: We recruited 232 cases (abortus imminens) and 232 controls (healthy pregnant), matched for age, body mass index, and parity. When complete blood count derived indices were evaluated to determine whether the pregnancy would result in miscarriage or not, only SII had discriminative power among SII, SIRI, PIV, NLR, PLR and MLR. (cut-off: &gt; 720; p: 0.039, sensitivity: 63%, specificity: 52%. Conclusion: High SII levels in maternal blood can predict continuation of pregnancy in patients diagnosed with threatened miscarriage. This emphasises the importance of maternal immune tolerance and the immune system in maintaining pregnancy. In patients with high SII, pregnancy can be maintained with additional treatments. However, further studies are needed to confirm our results.

#1416 Extracorporeal removal of per- and polyfluoroalkyl substances (PFAS) by hemoadsorption: in vitro kinetic model

Abstract Background and Aims Per- and polyfluoroalkyl substances (PFAS) are known water pollutants leading to potential public health consequences. High blood levels of PFAS have been associated with several pathological conditions including testicular and kidney cancer. Classic extracorporeal therapies have demonstrated limited efficiency and new approaches should be explored. In this study we studied the possible role of hemoadsorption to achieve a fast, safe and effective removal of PFAS from blood in patients with high blood levels. Method We developed an in vitro model of hemoadsorption to test the potential of PFAS removal by extracorporeal treatment. We recirculated a highly polluted batch of water (4 liters) through HA380 sorbent cartridge (Jafron Medical, Zuhai, China) for 120 minutes at a flow of 150 mL/min in a closed loop configuration (Fig. 1). We collected samples at different time points and analyzed 39 different PFAS compounds. Results For the PFAS compounds with concentrations significantly above normal, we observed a removal ratio close to 90% already within the first 60 minutes of circulation leading to almost complete elimination of all pollutants at 120 minutes (Fig. 2). RR is remarkably high already in the very early moments of the adsorption process. This is likely dependent on the interaction of the different solutes with the molecular structure of the sorbent. Conclusion The in vitro model of hemoadsorption suggests the possible application in vivo of this technique to reduce/normalize the concentrations of PFAS in patients exposed to water or environmental pollution.

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.

Perfluoroalkyl/Polyfluoroalkyl Substances: Links to Cardiovascular Disease Risk.

Conservative estimates by the World Health Organization suggest that at least a quarter of global cardiovascular diseases are attributable to environmental exposures. Associations between air pollution and cardiovascular risk have garnered the most headlines and are strong, but less attention has been paid to other omnipresent toxicants in our ecosystem. Perfluoroalkyl and polyfluoroalkyl substances (PFASs) are man-made chemicals that are extensively used in industrial and consumer products worldwide and in aqueous film-forming foam utilized in firefighting. As such, our exposure to PFAS is essentially ubiquitous. Given the long half-lives of these degradation-resistant chemicals, virtually, all people are carrying a body burden of PFAS. Health concerns related to PFAS are growing such that the National Academies of Sciences, Engineering and Medicine has recommended standards for clinical follow-up of individuals with high PFAS blood levels, including prioritizing screening for dyslipidemia. The link between PFAS and dyslipidemia has been extensively investigated, and evidence for associations is compelling. However, dyslipidemia is not the only cardiovascular risk factor with which PFAS is associated. Here, we review the epidemiological evidence for links between PFAS of concern identified by the National Academies of Sciences, Engineering and Medicine and risk factors for cardiovascular disease, including overweight/obesity, glucose intolerance, hypertension, dyslipidemia, and hyperuricemia. Moreover, we review the potential connections of PFAS with vascular disease and atherosclerosis. While observational data support associations between the National Academies of Sciences, Engineering and Medicine PFAS and selected cardiac risk factors, additional research is needed to establish causation and better understand how exposure to PFAS leads to the development of these conditions.

White adipose tissue, a novel antirheumatic target: Clues from its secretory capability and adipectomy-based therapy.

White adipose tissue (WAT) is involved in rheumatoid arthritis (RA). This study explored its potential as an antirheumatic target. WAT status of healthy and adjuvant-induced arthritis (AIA) rats were compared. The contribution of WAT to RA pathology was evaluated by pre-adipocyte transplant experiments and by dissecting perirenal fat pads of AIA rats. The impact of RA on WAT was investigated by culturing pre-adipocytes. Proteins differentially expressed in WAT of healthy and AIA rats were identified by the UPLC/MS2 method. These together with PPARγ siRNA and agonist were used to treat pre-adipocytes in vitro. The medium was used for THP-1 monocyte culture. Compared with healthy controls, AIA WAT was smaller but secreted more leptin, eNAMPT, MCP-1, TNF-α, and IL-6. AIA rat pre-adipocytes increased the levels of these adipokines in healthy recipients. RA patients' serum induced a similar secretion change and impaired differentiation of pre-adipocytes. Adipectomy eased AIA-related immune abnormalities and arthritic manifestations. Hepatokines PON1, IGFBP4, and GPIHBP1 were among the differential proteins in high levels in RA blood, and induced inflammatory secretions by pre-adipocytes. GPIHBP1 inhibited PPARγ expression and caused differentiation impairment and inflammatory secretion by pre-adipocytes, a similar outcome to PPARγ-silencing. This endowed the cells with an ability to activate monocytes, which can be abrogated by rosiglitazone. Certain hepatokines potentiate inflammatory secretions by pre-adipocytes and expedite RA progression by inhibiting PPARγ. Targeting this signalling or abnormal WAT secretion by various approaches may reduce RA severity.

PET/CT with &lt;sup&gt;18&lt;/sup&gt;F-FDG for TENIS Syndrome in a Patient with Bone Metastasis of Hurthle Cell Thyroid Cancer: a Clinical Case Report

A significant role in improving the prognosis of differentiated thyroid cancer (DTC) in the presence of bone metastases is determined by early diagnosis of metastases, timely and correctly selected treatment tactics for the patient. During dynamic follow-up of patients with DTC after combined treatment (thyroidectomy with radioiodine therapy) are determination of the level of oncomarkers (serum thyroglobulin and antibodies to thyroglobulin) and ultrasound diagnostic of the neck, scanning with radioactive iodine (if clinically indicated). In some cases, patients have TENIS-syndrome (Thyroglobulin Elevated Negative Iodine Scintigraphy, hereinafter TENIS-syndrome), characterized by high serum thyroglobulin level in blood and absence of radioactive iodine accumulation on post therapeutic scintigraphy. According to the research studies, PET/CT with 18F-FDG has high sensitivity and specificity (89 % and 72 %, respectively) in visualization of metastatic radioiodine refractory foci in TENIS-syndrome.This article presents a clinical case of a patient, a 52-year-old woman with Gurtle cell thyroid cancer (pT3aN0M0, stage I) with established TENIS syndrome. Thyroidectomy was performed in September 2019 and radioiodine therapy was performed in January 2022 due to suspected disease progression given high thyroglobulin levels. Given the absence of pathologic accumulation of 131I according to post-therapy radioiodine scanning, PET/CT with 18F-FDG was performed, which revealed a solitary metastasis in the left iliac bone (41×35×42 mm with SUVmax 17.25). In November 2022, radical treatment of the solitary bone metastasis was performed in the scope of resection of the left iliac bone with reconstructive-plastic component. According to the data of control examinations in June 2023, the patient has a complete biochemical and radiologic remission of the disease.

Extracorporeal Removal of Per- and Polyfluoroalkyl Substances by Hemoadsorption: In vitro Kinetic Model

Introduction: Per- and polyfluoroalkyl substances (PFAS) are known water pollutants leading to potential public health consequences. High blood levels of PFAS have been associated with several pathological conditions including testicular and kidney cancer. Classic extracorporeal therapies have demonstrated limited efficiency, and new approaches should be explored. In this study, we studied the possible role of hemoadsorption to achieve a fast, safe, and effective removal of PFAS from blood in patients with high blood levels. Methods: We developed an in vitro model of hemoadsorption to test the potential of PFAS removal by extracorporeal treatment. We recirculated a highly polluted batch of water (4 L) through a sorbent cartridge (Jafron Medical, Zhuhai, China) for 120 min at a flow of 150 mL/min. We collected samples at different time points and analyzed 39 different PFAS compounds. Results: For the PFAS compounds with concentrations significantly above normal, we observed a removal ratio close to 90% already within the first 60 min of circulation leading to almost complete elimination of all pollutants at 120 min. Conclusions: The in vitro model of hemoadsorption suggests the possible application in vivo of this technique to reduce/normalize the concentrations of PFAS in patients exposed to water or environmental pollution.

Low Density Lipoprotein Cholesterol Decreases the Expression of Adenosine A2A Receptor and Lipid Rafts-Protein Flotillin-1: Insights on Cardiovascular Risk of Hypercholesterolemia.

High blood levels of low-density lipoprotein (LDL)-cholesterol (LDL-C) are associated with atherosclerosis, mainly by promoting foam cell accumulation in vessels. As cholesterol is an essential component of cell plasma membranes and a regulator of several signaling pathways, LDL-C excess may have wider cardiovascular toxicity. We examined, in untreated hypercholesterolemia (HC) patients, selected regardless of the cause of LDL-C accumulation, and in healthy participants (HP), the expression of the adenosine A2A receptor (A2AR), an anti-inflammatory and vasodilatory protein with cholesterol-dependent modulation, and Flotillin-1, protein marker of cholesterol-enriched plasma membrane domains. Blood cardiovascular risk and inflammatory biomarkers were measured. A2AR and Flotillin-1 expression in peripheral blood mononuclear cells (PBMC) was lower in patients compared to HP and negatively correlated to LDL-C blood levels. No other differences were observed between the two groups apart from transferrin and ferritin concentrations. A2AR and Flotillin-1 proteins levels were positively correlated in the whole study population. Incubation of HP PBMCs with LDL-C caused a similar reduction in A2AR and Flotillin-1 expression. We suggest that LDL-C affects A2AR expression by impacting cholesterol-enriched membrane microdomains. Our results provide new insights into the molecular mechanisms underlying cholesterol toxicity, and may have important clinical implication for assessment and treatment of cardiovascular risk in HC.

An Analysis of the Gut Microbiota and Related Metabolites following PCSK9 Inhibition in Statin-Treated Patients with Elevated Levels of Lipoprotein(a).

Atherosclerotic cardiovascular disease (ASCVD) is a leading cause of global mortality, often associated with high blood levels of LDL cholesterol (LDL-c). Medications like statins and PCSK9 inhibitors, are used to manage LDL-c levels and reduce ASCVD risk. Recent findings connect the gut microbiota and its metabolites to ASCVD development. We showed that statins modulate the gut microbiota including the production of microbial metabolites involved in the regulation of cholesterol metabolism such as short chain fatty acids (SCFAs) and bile acids (BAs). Whether this pleiotropic effect of statins is associated with their antimicrobial properties or it is secondary to the modulation of cholesterol metabolism in the host is unknown. In this observational study, we evaluated whether alirocumab, a PCSK9 inhibitor administered subcutaneously, alters the stool-associated microbiota and the profiles of SCFAs and BAs. We used stool and plasma collected from patients enrolled in a single-sequence study using alirocumab. Microbial DNA was extracted from stool, and the bacterial component of the gut microbiota profiled following an amplicon sequencing strategy targeting the V3-V4 region of the 16S rRNA gene. Bile acids and SCFAs were profiled and quantified in stool and plasma using mass spectrometry. Treatment with alirocumab did not alter bacterial alpha (Shannon index, p = 0.74) or beta diversity (PERMANOVA, p = 0.89) in feces. Similarly, circulating levels of SCFAs (mean difference (95% confidence interval (CI)), 8.12 [-7.15-23.36] µM, p = 0.25) and BAs (mean difference (95% CI), 0.04 [-0.11-0.19] log10(nmol mg-1 feces), p = 0.56) were equivalent regardless of PCSK9 inhibition. Alirocumab therapy was associated with increased concentration of BAs in feces (mean difference (95% CI), 0.20 [0.05-0.34] log10(nmol mg-1 feces), p = 0.01). In statin-treated patients, the use of alirocumab to inhibit PCSK9 leads to elevated levels of fecal BAs without altering the bacterial population of the gut microbiota. The association of alirocumab with increased fecal BA concentration suggests an additional mechanism for the cholesterol-lowering effect of PCSK9 inhibition.