Search Results (6,156)

The gut-liver-adipose axis plays a pivotal role in metabolic regulation, and its dysregulation contributes to obesity and metabolic syndrome. Probiotics and polycosanol have shown potential in modulating gut barrier integrity, lipid metabolism, and inflammation. This study aimed to evaluate their combined effects using an in vitro model of the gut-liver-adipose axis. Transwell^® system was used to recreate the interaction between intestinal (CaCo-2), hepatic (HepG2), and adipose (3T3-L1) cells. Cells were treated with Bifidobacterium bifidum GM-25, Bifidobacterium infantis GM-21, Lacticaseibacillus rhamnosus GM-28, and polycosanols. The effects were assessed by analyzing intestinal barrier integrity (TEER, tight junction proteins), hepatic and adipose lipid accumulation (Oil Red O staining), oxidative stress (ROS production, lipid peroxidation), inflammation (TNF-α) and lipid metabolism (CD36, PPARγ, AMPK and SREBP-1 levels). Probiotics and polycosanols improved intestinal integrity, increased butyrate production, and reduced ROS levels. Hepatic lipid accumulation was significantly decreased, with enhanced PPARγ and AMPK activation. In adipocytes, probiotic-polycosanols treatment suppressed SREBP-1 expression, enhanced lipid oxidation, and promoted UCP1 and PGC-1α expression, suggesting activation of thermogenic pathways. These findings underline a possible biological relevance of probiotics and polycosanols in modulating metabolic pathways, improving gut barrier integrity, and reducing inflammation, supporting their role as functional ingredients for metabolic health. Full article

Maternal metabolic dysfunction adversely influences embryonic muscle oxidative capacity and mitochondrial biogenesis, increasing the child’s long-term risks of developing obesity and metabolic syndrome in later life. This pilot study explored the mechanistic basis of embryonic muscle metabolic programming, employing non-invasive magnetic field exposures. Brief (10 min) exposure to low-energy (1.5 milliTesla at 50 Hertz) pulsing electromagnetic fields (PEMFs) has been shown in mammals to promote oxidative muscle development, associated with enhanced muscular mitochondriogenesis, augmented lipid metabolism, and attenuated inflammatory status. In this study, quail eggs were used as a model system to investigate the potential of analogous PEMF therapy to modulate embryonic muscle oxidative capacity independently of maternal influence. Quail eggs were administered five 10-min PEMF exposures to either upward-directed or downward-directed magnetic fields over 13 days. Embryos receiving magnetic treatment exhibited increased embryo weight, size, and survival compared to non-exposed controls. Upward exposure was associated with larger embryos, redder breast musculature, and upregulated levels of PPAR-α and PGC-1α, transcriptional regulators promoting oxidative muscle development, mitochondriogenesis, and angiogenesis, whereas downward exposure augmented collagen levels and reduced angiogenesis. Exposure to upward PEMFs may hence serve as a method to promote embryonic growth and oxidative muscle development and improve embryonic mortality. Full article

Background: The muscles and their tendons exhibit considerable morphological variations. While the anterior leg compartment may seem uniform, several well-documented variants of the tibialis anterior, extensor hallucis longus (EHL) and extensor digitorum longus (EDL) exist. In contrast, little is known about the fibularis tertius muscle (FT). This literature review aims to compile existing data on the FT and its variations and assess this structure’s clinical significance. Material and Methods: This comprehensive literature review is based on scientific articles obtained from PubMed. All relevant papers were included, and citation tracking was conducted to ensure a thorough examination of the topic. Results: This detailed literature review synthesizes the latest scientific findings regarding the FT, exploring its variable morphology, functional anatomy, evolutionary significance and clinical relevance. A high morphological variability of the FT is described including its origin, insertion and accessory form. Nevertheless, the FT has been described in cadaveric studies between adults and fetuses, while few classification systems have been proposed. Conclusions: The FT is an intriguing structure that has garnered interest from researchers across various fields, including medicine, clinical practice and biological sciences. There are few clinical implications of the muscle such as FT syndrome or tendon tear. Adequate knowledge of its anatomy is of paramount importance for clinicians. Full article

Congenital Rubella Syndrome (CRS) results from maternal infection with the rubella virus during pregnancy, particularly in the first trimester, when the risk of vertical transmission and severe fetal damage is highest. CRS is characterized by a broad spectrum of congenital anomalies, including sensorineural hearing loss, congenital heart defects, cataracts, neurodevelopmental delay, and behavioral disorders. Despite the absence of specific antiviral therapies, active immunization remains the only effective strategy to prevent rubella infection and its congenital consequences. Global immunization efforts, particularly in the Americas, have led to the elimination of rubella and CRS in several countries. However, challenges persist in the post-elimination era, including declining vaccine coverage, vaccine hesitancy, and setbacks caused by the COVID-19 pandemic. Diagnosis relies on maternal serology, fetal imaging, postnatal antibody testing, and molecular techniques. Management requires long-term, multidisciplinary follow-up due to the complex and lifelong sequelae affecting sensory, motor, and cognitive development. This review highlights the clinical, epidemiological, and pathophysiological aspects of CRS, while emphasizing the urgent need to maintain high vaccination coverage and strengthen surveillance systems. Sustained public health commitment is essential to prevent the reemergence of rubella and protect future generations from this preventable syndrome. Full article

Macrophage activation syndrome (MAS) is a complex, life-threatening, hyperinflammatory condition occurring as a form of hemophagocytic lymphohistiocytosis (HLH), commonly associated with several autoimmune and autoinflammatory diseases, and certain infections such as Parvovirus B19 (P19V). The onset of systemic lupus erythematosus (SLE) presenting as MAS during pregnancy is uncommon, posing significant diagnostic and therapeutic challenges. We present a case of a 30-year-old woman at the 12th gestational week with fever, arthralgia, rash, cervical lymphadenopathy, cytopenia, and elevated liver enzyme. Bone marrow biopsy revealing hemophagocytosis, elevated ferritin and triglycerides, high interleukin-2, fever and cytopenia, confirmed the diagnosis of HLH. Further evaluation revealed the diagnosis of SLE. Treatment was initiated with intravenous immunoglobulin and corticosteroids. Given the deterioration in the patient’s clinical condition, a decision was made to terminate the pregnancy. She continued in the following months to receive SLE treatment with corticosteroids, cyclophosphamide, hydroxychloroquine, and later with mycophenolate mofetil due to the development of Class IV of lupus nephritis. P19V IgM antibodies were initially positive, later seroconverted to IgG, indicating that infection may have acted as a trigger for the onset of SLE and MAS development during pregnancy. The overlapping clinical features of P19V infection, SLE, and MAS pose significant diagnostic and therapeutic challenges. Early recognition and comprehensive diagnostic evaluation are crucial for the management of these conditions, especially during pregnancy, where both maternal outcomes are at risk. Full article

Hans Selye’s stress concept, first introduced in the 1930s, has undergone substantial evolution, extending beyond biology and medicine to influence diverse academic disciplines. Initially, Selye’s General Adaptation Syndrome (GAS) described nonspecific physiological responses to stressors exclusively in mammals, without addressing other biological systems. Consequently, the concept of stress developed independently in biology and medicine, shaped by distinct physiological contexts. This review provides a historical overview of stress research, highlights both parallels and divergences between the stress responses of plants and animals, and integrates insights from traditional Eastern philosophies. We propose an updated GAS framework that incorporates the dynamic balance among reactive oxygen species (ROS), reactive nitrogen species (RNS), and reactive sulfur species (RSS) within the broader context of oxidative stress. We highlight the ionotropic glutamate receptor (iGluR) family and the transient receptor potential (TRP) channel superfamily as minimal molecular architectures for achieving GAS. This perspective expands the classical stress paradigm, providing new insights into redox biology, interspecies stress adaptation, and evolutionary physiology. Full article

Background: Addison’s disease (AD) is a rare disorder that often develops in the context of autoimmune polyglandular syndromes. However, the prevalence of rheumatological autoimmune diseases and corresponding autoimmune markers in AD is poorly investigated. Therefore, the present study aims to explore systemic and organ-specific immune markers in a cohort of AD patients from a single tertiary endocrine center. Material and methods: In total, 43 adult AD patients and 31 controls were included in the study. 21-hydroxylase autoantibodies (21OHAb), glutamic acid decarboxylase autoantibodies (GADAbs), zinc transporter-8 autoantibodies (ZnT8Abs), antibodies against nuclear antigens (ANAs), autoantibodies against cyclic citrullinated peptides (CCPAbs), rheumatoid factors (RFs), IgG autoantibodies against cardiolipin (ACLAbs), and autoantibodies against beta-2-Glycoprotein I (β2-GPIAbs) were measured in all participants. Results: An increased prevalence of antibodies against RFs (27.91% vs. 0%, p < 0.001) and ANAs (13.95% vs. 0%, p = 0.037) was found in AD patients compared to controls. Moreover, the titers of 21-hydroxylase and RF antibodies correlated positively (r = +0.269, p = 0.020). The AD patients tended to show an increased prevalence of subthreshold ACL antibody reactivity compared to controls. All patients diagnosed with type 1 diabetes mellitus were GADAb- but not ZnT8Ab-positive. Conclusions: The results show an increased prevalence of ANA and RF positivity in AD patients compared to controls and a significant association between 21-OHAb and RF positivity. ZnT8Ab positivity was not typical for adult AD patients from our ethnic group, while GADAbs were an essential marker for autoimmune diabetes mellitus. Extensive studies in different ethnic groups are needed to establish the clinical significance of various immunological markers for AD comorbidity and the appropriate follow-up protocols for patients with different antibody positivity. Full article

Background/Objectives: The complement system (particularly C5b-9) is an instrumental part of the induction and progression of atherosclerosis. The fluid phase C5b-9, also known as soluble C5b-9 (sC5b-9), is a reliable indicator of terminal complement pathway activation. Response Gene to Complement (RGC)-32 is a C5b-9 effector involved in cell cycle regulation and differentiation, immunity, tumorigenesis, obesity, and vascular lesion formation. RGC-32 regulates the expression of Sirtuin1 (SIRT1), known to delay vascular aging. The aim of this study was to assess the levels of sC5b-9, RGC-32, and SIRT1 in patients with atherosclerotic chronic and acute ischemic coronary syndromes. Methods: We determined the levels of sC5b-9, serum RGC-32, and SIRT1 by enzyme-linked immunosorbent assays (ELISAs) in 41 patients with chronic atherosclerotic coronary syndromes, 36 patients with acute ischemic coronary syndromes, and 21 asymptomatic controls with no history of ischemic heart disease. Results: sC5b-9 was significantly higher in patients with acute coronary syndrome as compared to the control group (p = 0.020, AUC = 0.702). In chronic coronary ischemia patients, serum RGC-32 was correlated with the extension of coronagraphically visualized atherosclerotic lesions (r = 0.352, p = 0.035) as well as with sC5b-9 levels (r = 0.350, p = 0.025). RGC-32 concentration was significantly lower in patients with acute coronary syndrome than in the control group (p = 0.020). We also observed significantly lower serum SIRT1 concentrations in patients with chronic ischemic heart disease than in the control group (p = 0.025). Conclusions: sC5b-9 may function as a possible biomarker for myocardial tissue damage in acute coronary syndrome. In acute coronary syndrome settings, low levels of RGC-32 may indicate a protective, antifibrotic function of RGC-32 in the ischemia-damaged myocardium; however, in stable chronic disease, RGC-32 serum values appear to correlate with the extent of atherosclerotic lesions, suggesting a pro-atherogenic role for RGC-32. Chronic myocardial ischemia decreases SIRT1 protein levels in serum, which underscores the use of SIRT1-modulating drugs in these patients. Full article

Background: Low-dose antibiotic contamination in animal feed is a persistent global food safety challenge. Transient early-life exposure to low-dose penicillin (LDP) is known to induce metabolic syndrome (MetS) in adult mice, but the underlying mechanisms are unclear. Introduction: This study investigated the role of gut microbiota (GM) and intestinal immunity in mediating the long-term metabolic effects of early-life LDP exposure. Methods: Mice were exposed to LDP transiently during early life. GM composition was analyzed. Intestinal IgA responses were quantified. Bacterial encroachment, systemic and adipose tissue inflammation, and diet-induced MetS were assessed. Germ-free (GF) mice received GM transplants from LDP-exposed or control mice to test causality and persistence. Results: Early-life LDP exposure significantly disrupted GM composition, particularly in the ileum, in 30-day-old mice. These GM alterations caused persistent suppression of intestinal IgA responses, evidenced by reduced IgA-producing cells and sIgA levels. This suppression was constrained to early-life exposure: transferring LDP-modified GM to GF mice produced only a transient reduction in fecal sIgA. The LDP-induced sIgA reduction decreased IgA binding of bacteria, leading to increased bacterial encroachment and systemic and adipose tissue inflammation. These pathological changes exacerbated diet-induced MetS. Discussion: Our findings demonstrate that early-life LDP exposure induces persistent intestinal IgA deficiency through lasting GM alterations initiated in early development. This deficiency drives bacterial encroachment, inflammation, and ultimately exacerbates MetS. Conclusions: The exacerbation of diet-induced metabolic syndrome by early-life LDP exposure occurs through an intestinal sIgA-dependent pathway triggered by persistent GM disruption. This highlights a critical mechanism linking early-life antibiotic exposure, gut immune dysfunction, and long-term metabolic health, with significant implications for food safety. Full article

Background: This study examined the incidence of acute complications within the first year following combat-related lower extremity injuries in United States (U.S.) Service members (SMs). The research compared outcomes between primary amputation (PA), limb salvage (LS), and non-threatening limb trauma (NTLT) groups, and conducted a subgroup analysis within the LS group, differentiating between SM who underwent a secondary amputation (LS-SA) and those who did not (LS-NA). Methods: A retrospective analysis of combat-related lower extremity injuries sustained between January 2001 and October 2015 was performed using data from the Military Health System Medical Data Repository. Chi-square tests and adjusted logistic regression analysis were used to compare complication frequencies by injury severity. Results: The analysis of the 4275 SM revealed that 21% had undergone PA, 47% LS (with 13% experiencing LS-SA and 87% LS-NA), and NTLT was observed in 32% of cases. The PA group exhibited higher rates of most acute complications compared to other groups, with three exceptions—i.e., non-union fractures, compartment syndrome, and orthopedic device complications were more prevalent in the LS group than the PA group. The LS-SA group had higher complication rates than the LS-NA group for most complications. Notably, the PA group was associated with the highest rates of post-hemorrhagic anemia and heterotopic ossification, while the LS-SA group exhibited the highest rates of osteomyelitis, non-union fractures, non-healing wounds, and compartment syndrome. Conclusions: Individuals with amputation (PA or LS-SA) were more likely to experience acute complications compared to their counterparts (PA vs. LS and NTLT; LS-SA vs. LS-NA), with the exception of non-union fractures, which were more frequent in the LS group than the PA group. These findings highlight the need for close monitoring and targeted interventions to address post-surgical complications in Service members with limb salvage. Full article

Endometrial organoids (EOs) have emerged as a powerful three-dimensional (3D) model for studying the human endometrium, offering new insights into infertility and reproductive disorders. These self-organizing miniature structures closely mimic the cellular composition, hormonal responsiveness, and functional characteristics of the endometrium, making them valuable preclinical tools for investigating implantation failure, endometrial receptivity, and disease pathophysiology. This review explores the role of EOs in reproductive medicine, with a focus on their applications in infertility research, environmental toxicology, and regenerative therapies. Traditional 2D cell cultures fail to capture the complexity of these physiological and pathological interactions, whereas organoids provide a physiologically relevant system for studying implantation mechanisms. Additionally, co-culture models incorporating stromal and immune cells have further enhanced our understanding of the maternal–fetal interface. Beyond modeling infertility, EOs hold significant promise for therapeutic applications. Advances in organoid transplantation have demonstrated potential for treating endometrial dysfunction-related infertility, including conditions such as Asherman’s syndrome and thin endometrium. Moreover, these models serve as a platform for drug screening and biomarker discovery, paving the way for personalized reproductive medicine. Despite their transformative potential, limitations remain, including the need for improved extracellular matrices, vascularization, and immune system integration. This review emphasizes the significant contributions of EOs to the field of infertility treatment and reproductive biology by examining recent advancements and emerging research. The continued refinement of these models would offer a paradigm for improving assisted reproductive technologies (ARTs) and regenerative medicine outcomes, offering new hope for individuals facing infertility challenges. Full article

Post-COVID-19 is a chronic infection-related syndrome, including exacerbations of pre-existing or newly diagnosed conditions that have been established after the acute phase of COVID-19 and have demonstrated a wide range of systemic effects beyond the lungs. SARS-CoV-2 attaches to its receptor, angiotensin-converting enzyme 2 (ACE-2). Transmembrane serine protease 2 (TMPRSS2) facilitates viral entry and spread. ACE-2 receptors are detectable in several tissues, including the respiratory mucosa, digestive tract, heart, kidney, and brain. Several investigations have demonstrated an increase in digestive manifestations post-acute COVID-19, likely related to an alteration in the intestinal microbiota following infection. These changes can lead to a loss of species diversity, resulting in an overgrowth of opportunistic pathogens and deprivation of commensal bacteria. In this context, post-infection irritable bowel syndrome shows an increased incidence compared to controls. Growing evidence also suggests the enduring presence of SARS-CoV-2 in the gut tissue. Studies are ongoing to investigate antiviral agents that counteract prolonged COVID-19 symptoms. Therefore, the objectives of this review were to summarize the digestive manifestations, focusing on irritable bowel syndrome and therapeutic strategies. This review gives an overview of studies published in English in the last two years on the PubMed database. Full article

Myelodysplastic syndromes (MDS) belong to a category of malignant stem-cell and myeloid disorders that deteriorate the function of the hematopoietic system exacerbated by the omnipresent anemia that characterizes myelodysplasia. The pathogenesis of MDS is driven by cytogenetic abnormalities along with the excessive production of pro-inflammatory cytokines and disruptions in inflammatory signaling pathway, particularly through the influence of carbonylated proteins, which are linked to MDS progression. An additional and major contributor to the pathogenesis of MDS is oxidative stress marked by uncontrolled levels of reactive oxygen species (ROS), which have been suggested as potential biomarkers for assessing disease severity and stratifying MDS cases throughout a variety of methods. Excessive and non-accumulative levels of free iron can also lead to iron overload (IOL)—related promotion of a high oxidative state, whether we refer to treatment-related IOL or natural IOL mechanisms. Proteomic analysis has emerged as a powerful tool for profiling protein samples, and, consequently, understanding the molecular changes underlying MDS. In this review, we evaluated studies and their methodologies aiming in investigating distinctive proteomics signatures associated with MDS pathogenesis, focusing on the role of oxidative stress at the protein level. Full article

The liver and kidneys are two of the most vital organs, each with distinct but overlapping functions essential for maintaining homeostasis. The complex interplay between these organs, commonly referred to as liver-kidney crosstalk, plays a crucial role in the pathophysiology of several acute and chronic conditions in childhood. Despite its importance, the precise biological mechanisms driving this interaction remain incompletely understood. This crosstalk is particularly significant in various pediatric diseases (e.g., Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), Hepatorenal Syndrome (HRS), genetic and metabolic disorders, etc.) where shared pathophysiological factors—including systemic inflammation, metabolic disturbances, oxidative stress, and vascular dysfunction—simultaneously affect both organs. Clinically, this interaction presents unique challenges in diagnosing, managing, and treating liver-kidney diseases in affected children. Understanding the pathogenic mechanisms underlying liver-kidney crosstalk is essential for improving patient care and outcomes through an integrated, multidisciplinary approach and personalized treatment strategies. This review aims to explore liver-kidney crosstalk in key pediatric diseases, offering a comprehensive overview of current knowledge, clinical challenges, and potential therapeutic interventions in this complex field. Full article

Background/Objectives: The pharmacokinetics of vancomycin (VCM) in patients with febrile neutropenia (FN) are highly variable due to coexisting conditions such as systemic inflammatory response syndrome and augmented renal clearance. Upon hematopoietic recovery, VCM clearance (CLvcm) is expected to normalize, which contributes to intra-individual variability. This study aimed to investigate the factors contributing to intra-individual variability in CLvcm among pediatric patients with FN. Methods: This retrospective, single-center study analyzed 33 pediatric patients (48 FN episodes) who met the inclusion criteria. CLvcm was estimated using Bayesian estimation based on the pediatric population pharmacokinetic model developed by Le et al., and standardized with allometrically scaled body weight. The change (Δ) in each clinical laboratory parameter or CLvcm was calculated as the difference between the values at the current and previous TDM within the same episode. Results: A total of 155 VCM TDM data points were analyzed. Intra-individual comparisons revealed that CLvcm decreased significantly in patients recovering from FN to a non-FN state (n = 18, p = 0.0285). Further analysis of intra-individual variability revealed that Δ CLvcm correlated significantly with Δ hemoglobin, Δ C-reactive protein, and Δ maximum daily body temperature, with the strongest correlation observed for Δ maximum daily body temperature (rs = 0.325, p = 0.001). Multivariate analysis confirmed Δ maximum daily body temperature as a significant factor influencing Δ CLvcm (B = 0.376, 95% CI: 0.074 to 0.678, p = 0.015). Conclusions: Maximum daily body temperature was identified as a factor influencing intra-individual variability in CLvcm in pediatric FN patients, particularly during the recovery process from FN to a non-FN state. The finding suggests that dose adjustment based on maximum daily body temperature may allow safe and effective VCM therapy in FN patients. Full article