Search Results (28,304)

Background: Hypoparathyroidism with hypocalcemia is the most frequent complication after thyroid surgery. Many risk factors have been involved in the development of this complication, with conflicting results. Incidental parathyroidectomy (IP) may be a frequent cause of postoperative hypocalcemia. In this study, we have evaluated the risk factors associated with the IP in a single-center cohort of patients undergoing thyroid surgery. Patients and methods: The incidence and the risk factors for IP were evaluated in 799 patients scheduled for surgical treatment for thyroid disease between January 2018 and December 2023. Parathyroid hormone levels and serum calcium levels, together with the histological specimens, were evaluated in all patients. Results: Post-operative temporary hypocalcemia was present in 239 (29.9%) patients. A total of 144 patients (21.9%) had an incidental parathyroidectomy. Younger patients (<40 years) had the highest risk of having an incidental parathyroidectomy (RR 1.53 (95% CI 1.084–2.161), OR 1.72 (95% CI 1.091–2.710), p = 0.014). Moreover, thyroid cancer (RR 1.4 (95 CI 1.114–1.882) OR 1.68 (95% CI 1.145–2.484), p < 0.05) and the neck dissection (RR 1.75 (95% CI 1.409–2.198) OR 2.38 (95% CI 1.644–3.460), p < 0.001) were strongly associated with the risk of incidental parathyroidectomy. Conclusions: Younger female patients with thyroid cancer and neck dissection were at the highest risk of incidental parathyroidectomy. A meticulous surgical dissection, together with imaging methods for the detection of the parathyroid glands, may reduce the incidence of this complication. Full article

Background: The multisystemic features of Down syndrome (DS) in children are accompanied by immunodeficiency, making them susceptible to infections and immune dysregulation with autoimmune, allergic, inflammatory, and hematological complications. This study was aimed at a better understanding of the abnormalities within the B and T cell compartments and their correlations with clinical immunophenotypes. Methods: Medical records of 35 DS children were retrospectively reviewed, referring to clinical symptomatology including history of infections, immune dysregulation disorders, and humoral and cellular immune response. Results: While the etiology of respiratory tract infections included typical viral and bacterial pathogens, SARS-CoV2-induced inflammatory disease and syndromic immunodeficiency contributed significantly to the deterioration of the clinical course. Allergic diseases in the form of asthma, allergic rhinitis, and alimentary allergy were the most frequent manifestations of immune dysregulation and were followed by autoimmune disorders, such as Crohn’s disease, celiac disease, autoimmune thyroiditis, and alopecia, as well as inflammatory disorders, balanitis xerotica obliterans and lymphadenopathy, and a hematological disorder of myelopoiesis. Deficiency of serum immunoglobulin levels, reduced numbers of naïve B cells, and non-switched memory B cells along with low naïve T helper cells and significantly reduced regulatory T helper cells were the most prominent immune abnormalities. Conclusions: The loss of naïveté in B and T lymphocyte compartments with a deficiency of regulatory T cells may be underpinning pathomechanisms for the skewed immune response. The clinical immunophenotype in DS is complex and represents syndromic primary immunodeficiency with immune dysregulation. Full article

Serum amyloid A (SAA) is one of the most important precursor amyloid proteins discovered during the study of amyloidosis, but its underlying aggregation mechanism has not yet been well elucidated. Since SAA aggregation is a key step in the pathogenesis of AA amyloidosis, amyloid inhibitors can be used as a tool to study its pathogenesis. Previously, we reported a novel microliter-scale high-throughput screening (MSHTS) system for screening amyloid β (Aβ) aggregation inhibitors based on quantum dot (QD) fluorescence imaging technology. In this study, we report the aggregation of human SAA (hSAA) in phosphate-buffered saline, in which we successfully visualized hSAA aggregation by QD using fluorescence microscopy and confocal microscopy. Two-dimensional and three-dimensional image analyses showed that most aggregations were observed at 40 μM hSAA, which was the optimal aggregation concentration in vitro. The accuracy of this finding was verified by a Thioflavin T assay. The transmission electron microscopy results showed that QD uniformly bound to hSAA aggregation. hSAA aggregation inhibitory activity was also evaluated by rosmarinic acid (RA). The results showed that RA, which is a compound with high inhibitory activity against Aβ aggregation, also exhibited high inhibitory activity against 40 μM hSAA. These results indicate that the MSHTS system is an effective tool for visualizing hSAA aggregation and for screening highly active inhibitors. Full article

Sepsis is an exaggerated immune response resulting from systemic inflammation, which can damage tissues and organs. Acute kidney injury has been detected in at least one-third of patients with sepsis. Sepsis-associated acute kidney injury increases the risk of a secondary infection. Rapid diagnosis and appropriate initiation of antibiotics can significantly reduce mortality and morbidity. However, microorganisms are known to develop resistance to antibiotics. Estimations indicate that the annual casualties caused by microbial resistance will surpass cancer fatalities by 2050. The prevalence of bacterial infections and their growing antibiotic resistance has brought immediate attention to the search for novel treatments. Plant-derived supplements contain numerous bioactive components with therapeutic potential against a variety of conditions, including infections. Punica granatum peel is rich in phenolic compounds. The purpose of this study was to determine the anti-inflammatory and anti-bacterial properties of P. granatum peel extract (PGPE) on lipopolysaccharide (LPS)-induced acute kidney injury. Experimental groups were Control, LPS (10 mg/kg LPS, intraperitoneally), PGPE100, and PGPE300 (100 and 300 mg/mL PGPE via oral gavage, respectively, for 7 days). According to biochemical results, serum blood urea nitrogen (BUN), creatinine (Cr) and C-reactive protein (CRP), kidney tissue thiobarbituric acid reactive substances (TBARS), and reduced glutathione (GSH) levels significantly decreased in the PGPE groups compared to the LPS group. Histopathological and immunohistochemical findings revealed that toll-like receptor 4 (TLR4) level and nuclear factor kappa B (NF-κB) expression increased in the LPS group compared to the Control group. In addition, the anti-Gram-negative activity showed a dose-dependent effect on Acinetobacter baumannii, Escherichia coli, and Pseudomonas aeruginosa with the agar well diffusion method and the minimal inhibitory concentration (MIC). The MIC value was remarkable, especially on A. baumannii. We conclude that PGPE has the potential to generate desirable anti-bacterial and anti-inflammatory effects on LPS-induced acute kidney injury in rats. Full article

Background/objective: Amyotrophic lateral sclerosis (ALS) is a diagnosis that incorporates a heterogeneous set of neurodegenerative processes into a single progressive and uniformly fatal disease making the development of a uniformly applicable therapeutic difficult. Recent multinational ALS natural history incidence studies have identified systemic chronic activation of the innate immune system as a major risk factor for developing ALS. Persistent immune activation in patients with ALS leads to loss of muscle and lowering of serum creatinine. The goal of the current study was to test whether the slowing of nerve and muscle destruction in NP001-treated ALS patients compared with controls in phase 2 studies would lead to extension of survival. Methods: Phase 2 clinical studies with NP001, an intravenously administered form of the innate immune system regulator NaClO₂, are now reporting long-term survival benefits for drug recipients vs. placebo controls after only six months of intermittent treatment. As a prodrug, NP001 is converted by macrophages to taurine chloramine, a long-lived regulator of inflammation. We performed a pooled analysis of all patients who had completed the studies in two six-month NP001 phase 2 trials. Changes in respiratory vital capacity and the muscle mass product, creatinine, defined treated patients who, compared to placebo, had up to a year of extended survival. Conclusions: The observed longer survival in ALS patients with the greatest inflammation-associated muscle loss provides further evidence that ALS is a disease of ongoing innate immune dysfunction and that NP001 is a disease-modifying drug with sustained clinical activity. Full article

Shigellosis represents a significant global health concern particularly affecting children under 5 years in low- and middle-income countries (LMICs) and is associated with stunting and antimicrobial resistance. There is a critical need for an effective vaccine offering broad protection against the different Shigella serotypes. A correlate of protection has not yet been established but there is a general consensus about the relevant role of anti-O-Antigen-specific IgG and its functionality evaluated by the Serum Bactericidal Assay (SBA). This study aims to characterize a high-throughput luminescence-based SBA (L-SBA) against seven widespread Shigella serotypes. The assay was previously developed and characterized for S. sonnei and S. flexneri 1b, 2a, and 3a and has now been refined and extended to an additional five serotypes (S. flexneri 4a, 5b, 6, X, and Y). The characterization of the assay with human sera confirmed the repeatability, intermediate precision, and linearity of the assays; both homologous and heterologous specificity were verified as well; finally, limit of detection and quantification were established for all assays. Moreover, different sources of baby rabbit complement showed to have no impact on L-SBA output. The results obtained confirm the possibility of extending the L-SBA to multiple Shigella serotypes, thus enabling analysis of the functional response induced by natural exposure to Shigella in epidemiological studies and the ability of candidate vaccines to elicit cross-functional antibodies able to kill a broad panel of prevalent Shigella serotypes in a complement-mediated fashion. Full article

Heavy metal contamination in agricultural soils presents serious environmental and health risks. This study assessed the bioaccumulation and spatial distribution of nickel, cadmium, zinc, lead, and copper within a sheep-based food chain in the Baia Mare region, Romania, which includes soil, green grass, sheep serum, and dairy products. Using inductively coupled plasma mass spectrometry (ICP-MS), we analyzed the concentrations of these metals and calculated bioconcentration factors (BCFs) to evaluate their transfer through trophic levels. Spatial analysis revealed that copper (up to 2528.20 mg/kg) and zinc (up to 1821.40 mg/kg) exceeded permissible limits, particularly near former mining sites. Elevated lead (807.59 mg/kg) and cadmium (2.94 mg/kg) were observed in industrial areas, while nickel and cobalt showed lower concentrations, but with localized peaks. Zinc was the most abundant metal in grass, while cadmium transferred efficiently to milk and cheese, raising potential health concerns. The results underscore the complex interplay between soil properties, contamination sources, and biological processes in heavy metal accumulation. These findings highlight the importance of continuous monitoring, risk assessment, and mitigation strategies to protect public health from potential exposure through contaminated dairy products. Full article

Background: Metabolic syndrome (MetS) is a set of conditions associated with an increased cardiovascular risk. Several serum fatty acids (FAs) seem to play an essential role in the development of cardiometabolic diseases and mortality. Thus, it is imperative to explore the impact of FAs on MetS parameters, using an early MetS screening tool such as MetScore, which is readily available in clinical practice. Aim: The aim of this study was to assess the potential correlation between serum FAs and cardiovascular risk using a MetScore. Methods: This cross-sectional study involved 41 women with severe obesity. The MetScore was calculated, and participants were categorized into high- and low-cardiovascular-risk groups based on the median MetScore value. Gas chromatography was used to quantify serum FAs. Generalized Linear Models were used to compare group means. The association was assessed through simple logistic regression, and an adjusted logistic regression was conducted to validate the association between Metscore and serum FAs. Results: The high-cardiovascular-risk group exhibited elevated values of HOMA-IR, palmitic, oleic, cis-vaccenic, and monounsaturated fatty acids, as well as the SCD-18C, indicating a heightened cardiovascular risk. Conversely, HDL-c, QUICK, gamma-linolenic, and eicosatetraenoic fatty acids showed lower values compared to the low-risk group. Conclusions: Women with severe obesity and high cardiovascular risk have lower values of some omega-3 and omega-6 FAs, considered cardioprotective and anti-inflammatory, and have higher lipogenic activity and FAs, correlated with high cardiovascular risk. These findings emphasize the need to address lipid metabolism in this population as a therapeutic target to reduce cardiovascular risk. Future research should explore clinical interventions that modulate fatty acid metabolism to mitigate cardiometabolic complications. Full article

(1) Introduction: Toll-like receptors (TLRs) are key in immune response by recognizing pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). In gastric cancer (GC), TLR2, TLR3, TLR4, and TLR9 are crucial for modulating immune response and tumor progression. (2) Objective: This study aimed to assess the percentage of dendritic cells and monocytes expressing TLR2, TLR3, TLR4, and TLR9, along with the concentration of their soluble forms in the serum of GC patients compared to healthy volunteers. Factors such as disease stage, tumor type, age, and gender were also analyzed. (3) Materials and Methods: Blood samples from newly diagnosed GC patients and healthy controls were immunophenotyped using flow cytometry to assess TLR expression on dendritic cell subpopulations and monocytes. Serum-soluble TLRs were measured by ELISA. Statistical analysis considered clinical variables such as tumor type, stage, age, and gender. (4) Results: TLR expression was significantly higher in GC patients, except for TLR3 on classical monocytes. Soluble forms of all TLRs were elevated in GC patients, with significant differences based on disease stage but not tumor type, except for serum TLR2, TLR4, and TLR9. (5) Conclusions: Elevated TLR expression and soluble TLR levels in GC patients suggest a role in tumor pathogenesis and progression, offering potential biomarkers and therapeutic targets. Full article

Background/Objectives: Lipid metabolism and adiponectin modulate erythropoiesis in vitro and in general population studies and may also affect responsiveness to erythropoietin in patients undergoing haemodialysis (HD). However, little is known about the impact of lipid-associated biomarkers on reticulocyte production and erythropoietin resistance index (ERI) in patients undergoing HD. Therefore, we aimed to investigate their impacts in 167 stable patients undergoing HD. Methods: Pre-dialysis blood samples were collected and analysed for reticulocyte counts and serum lipid profiles by routine analyses and serum carnitine profiles (C0–C18) by LC-MS/MS. ERI was calculated as erythropoietin dose/kg/week normalized for haemoglobin levels. Results: The independent positive determinants of reticulocyte count were log [Triglyceride (TG)] and logC18:1. A large proportion of longer-chain acylcarnitines was positively correlated with reticulocyte counts, possibly resulting from the accumulation of acylcarnitines in mitochondria undergoing fateful exocytosis from reticulocytes. These results indicate a possible association between reticulocyte formation and reduced β-oxidation, which occurs during the peripheral phase of erythroblast enucleation. Total cholesterol (TC) and log [C2/(C16 + C18:1)] as a putative marker of β-oxidation efficiency were negative independent determinants of ERI. Moreover, acyl chain length had a significantly positive impact on the correlation coefficients of individual acylcarnitines with ERI, suggesting that enhanced β-oxidation may be associated with reduced ERI. Finally, adiponectin had no independent association with reticulocyte counts or ERI despite its negative association with HDL-C levels. Conclusions: Enhanced fatty acid β-oxidation and higher TC levels may be associated with lower ERI, whereas higher TG levels and longer acylcarnitines may be related to the latest production of reticulocytes in stable patients undergoing HD. Full article

Differences in metabolic regulation among obesity phenotypes, specifically metabolically healthy obese (MHO) and metabolically unhealthy obese (MUO) women, may lead to varied responses to interventions, which could be elucidated through metabolomics. Therefore, this study aims to investigate the differences in metabolite profiles between MHO and MUO women and the changes following a lifestyle intervention. Serum samples from 36 MHO and 34 MUO women who participated in a lifestyle intervention for weight loss were analysed using untargeted proton nuclear magnetic resonance spectroscopy (¹H NMR) at baseline and 6 months post-intervention. Anthropometric, clinical, and dietary intake parameters were assessed at both time points. Both groups showed differential metabolite profiles at baseline and after six months. Seven metabolites, including trimethylamine-N-oxide (TMAO), arginine, ribose, aspartate, carnitine, choline, and tyrosine, significantly changed between groups post-intervention, which all showed a decreasing pattern in MHO. Significant reductions in body weight and body mass index (BMI) in the MUO correlated with changes in the carnitine and tyrosine levels. In conclusion, metabolite profiles differed significantly between MHO and MUO women before and after a lifestyle intervention. The changes in carnitine and tyrosine levels in MUO were correlated with weight loss, suggesting potential targets for therapeutic intervention. Full article

Atherosclerosis, as the main root cause, makes cardiovascular diseases (CVDs) a substantial worldwide health concern. Inflammation and disrupted cholesterol metabolism are the primary clinical risk elements contributing to the onset of atherosclerosis. Few works exist on the improvement effect of gut microbiota on atherosclerosis. One specific probiotic strain, Enterococcus faecium NCIMB11508, has shown promise in mitigating inflammation. Consequently, it is critical to investigate its potential in reducing the progression of atherosclerosis. In our study, we administered E. faecium NCIMB11508 orally to ApoE^−/− mice, resulting in a decrease in the formation of atherosclerotic lesions. Additionally, it demonstrated the ability to lower the inflammatory factor levels both in the aorta and blood serum while maintaining the integrity of the small intestine against lipopolysaccharides. Moreover, E. faecium NCIMB11508 had a beneficial impact on the gut microbiota composition by increasing the levels of short-chain fatty acids (SCFAs), which in turn helped to reduce inflammation and protect the intestine. The probiotic E. faecium NCIMB11508, according to our research, has a definitive capacity to prevent atherosclerosis progression by beneficially altering the SCFA composition in the gut microbiota of ApoE^−/− mice. Full article

Neutrophil extracellular traps (NETs) are intricate, DNA-based, web-like structures adorned with cytotoxic proteins. They play a crucial role in antimicrobial defense but are also implicated in autoimmune diseases and tissue injury. The process of NET formation, known as NETosis, is a regulated cell death mechanism that involves the release of these structures and is unique to neutrophils. NETosis is heavily dependent on the production of reactive oxygen species (ROS), which can be generated either through NADPH oxidase (NOX) or mitochondrial pathways, leading to NOX-dependent or NOX-independent NETosis, respectively. Recent research has revealed an intricate interplay between ROS production, DNA repair, and NET formation in different contexts. UV radiation can trigger a combined process of NETosis and apoptosis, known as apoNETosis, driven by mitochondrial ROS and DNA repair. Similarly, in calcium ionophore-induced NETosis, both ROS and DNA repair are key components, but only play a partial role. In the case of bacterial infections, the early stages of DNA repair are pivotal. Interestingly, in serum-free conditions, spontaneous NETosis occurs through NOX-derived ROS, with early-stage DNA repair inhibition halting the process, while late-stage inhibition increases it. The intricate balance between DNA repair processes and ROS production appears to be a critical factor in regulating NET formation, with different pathways being activated depending on the nature of the stimulus. These findings not only deepen our understanding of the mechanisms behind NETosis but also suggest potential therapeutic targets for conditions where NETs contribute to disease pathology. Full article

Liver diseases cause millions of deaths globally. Current treatments are often limited in effectiveness and availability, driving the search for alternatives. Herbal preparations offer potential hepatoprotective properties. Disrupted gut microbiota is linked to liver disorders. This scoping review aims to explore the effects of herbal preparations on hepatoprotective mechanisms, particularly in the context of non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), and hepatic steatosis, with a focus on gut microbiota modulation. A systematic search was performed using predetermined keywords in four electronic databases (PubMed, Scopus, EMBASE, and Web of Science). A total of 55 studies were included for descriptive analysis, covering study characteristics such as disease model, dietary model, animal model, intervention details, comparators, and study outcomes. The findings of this review suggest that the hepatoprotective effects of herbal preparations are closely related to their interactions with the gut microbiota. The hepatoprotective mechanisms of herbal preparations are shown through their effects on the gut microbiota composition, intestinal barrier, and microbial metabolites, which resulted in decreased serum levels of liver enzymes and lipids, improved liver pathology, inhibition of hepatic fatty acid accumulation, suppression of inflammation and oxidative stress, reduced insulin resistance, and altered bile acid metabolism. Full article

Objectives: Prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) has gained a primary role in prostate cancer (PCa) imaging, overcoming conventional imaging and prostate-specific antigen (PSA) serum levels, and has recently emerged as a promising technique for monitoring therapy response in metastatic castration-resistant prostate cancer (mCRPC) patients treated with novel hormonal therapy, taxanes, and radioligand therapy (RLT). In this review, we aim to provide an overview of the most relevant aspects under study and future prospects related to the prognostic role of PSMA PET/CT in mCRPC. Methods: A systematic literature search was performed in the following databases: MEDLINE, PubMed, and EMBASE databases. The study focused exclusively on English-language studies, excluding papers not pertinent to the topic. Results: PSMA PET imaging offers a higher sensitivity and specificity than conventional imaging and provides accurate staging and efficient diagnosis of distant metastases. The data presented herein highlight the usefulness of PET in risk stratification, with a prognostic potential that can have a significant impact on clinical practice. Several prospective trials are ongoing and will shortly provide more evidence supporting the prognostic potential of PET PSMA data in this clinical scenario. Conclusions: Current evidence proves the prognostic role of PSMA PET/CT in different settings, with raising relevance also in the context of mCRPC. Full article