Search Results (1,030)

Depression and osteoporosis frequently co-occur, presenting a significant and increasing clinical challenge, especially among older adults. Growing research highlights the bone–brain axis, a complex bidirectional communication network connecting the skeletal and central nervous systems, as a central mechanism linking these conditions. This review comprehensively examines the current knowledge of the molecular and cellular pathways within this axis that contribute to depression–osteoporosis interactions. It details how depression promotes bone loss through sustained hypothalamic–pituitary–adrenal axis activation, sympathetic nervous system overactivity, and chronic low-grade inflammation. This review also explores how bone-derived factors, including osteocalcin, lipocalin 2, and extracellular vesicles, cross the blood–brain barrier to influence brain function by regulating hippocampal neurogenesis, serotonin signaling, and neuroinflammation. This bidirectional communication is modulated by circadian rhythms and genetic factors. Understanding these pathways offers critical insights into the shared pathophysiology and reveals promising therapeutic targets. Interventions such as neuromodulation, customized exercise programs, and novel treatments focusing on bone-derived signals show potential for simultaneously addressing both mood disorders and bone health deterioration. This review emphasizes the need for an integrated system-based approach in clinical care that moves beyond traditional specialty-focused treatment to improve overall health outcomes, particularly for vulnerable elderly individuals. Full article

Background/Objectives: The increasing prevalence of overweight and obesity in adolescents represents a major global health concern. Adolescent weight gain frequently shows additional metabolic risk factors, including insulin resistance, hypertension, and dyslipidemia, whose co-occurrence defines the metabolic syndrome (MetS). Adherence to a healthy dietary pattern, such as the Mediterranean Diet (MD), has been shown to reduce the metabolic risk among adolescents. Skin carotenoid score has emerged as an objective and non-invasive indicator of MD adherence; however, its relationship with a cluster of metabolic parameters which characterize the MetS, including the triglyceride levels, diastolic blood pressure, and waist circumference, remains poorly explored. Here, we investigated the role of skin carotenoid score as an early biomarker of metabolic syndrome risk in adolescents. Methods: A sample of 634 healthy adolescents underwent anthropometric and clinical measurements, blood sample collection, and evaluation of the MD adherence by the Mediterranean Diet Quality Index for Children and Adolescents (KIDMED) questionnaire and the skin carotenoid levels by the Veggie Meter^®. Student’s t-test, chi-square test, Pearson correlation, and the multivariable linear regression model were used for analyses. Results: Participants had a mean BMI Z-score of 0.02 ± 1.01; the metabolic serum profile and the cardiovascular parameters were within the normal range. Mean KIDMED and skin carotenoid scores were 5.21 ± 2.56 and 357 ± 96.58, respectively. Skin carotenoids were positively associated with height (p = 0.02), while they were inversely associated with weight (p = 0.008), BMI Z-score (p < 0.0001), diastolic blood pressure (p = 0.013), and triglycerides (p = 0.003). Moreover, the carotenoid score was positively associated with male gender and KIDMED score and negatively associated with waist circumference and triglyceride levels in multivariable regression analyses. Conclusions: Our results suggested the potential application of skin carotenoid score as a complementary biomarker for the early identification of adolescents at increased metabolic risk. Full article

Background/Objectives: Liver cancer is among the most frequent poor-prognosis malignancies worldwide, with currently insufficient effective treatment. The two-stage microwave hyperthermia using magnetic nanoparticles is a modern technique designed to specifically target tumor tissues and facilitate chemotherapy activation, with promising results from fundamental studies across various tumor types. The method consists of a first irradiation, performed before nano-assemblies administration. This is intended to sensitize the tumor by inducing a hyperthermic effect, leading to increasing blood supply, enhancing endothelial damage/permeation and inflammatory activation, with the final goal of improving the diffusion/retention of nano-assemblies in the tumor. Subsequently, the second microwave irradiation follows the injection in the hepatic artery and diffusion in the tumor of the activated nano-assemblies, to further determine a strong, but localized and focalized hyperthermic action. Nano-magnetic assemblies for hyperthermia accomplish the proposed chemo-thermal delivery, i.e., act per se on the tumor and also destabilize co-administered assemblies of nanoparticles loaded with chemotherapeutics, which would be consequently released locally in the most efficient way. This article aims to demonstrate the efficacy of this therapeutic approach in a rat liver model and its potential applicability in patients with liver tumors. Methods: Adult male Wistar rats were used to obtain liver samples, which were divided into three groups, each receiving a different hyperthermia protocol in terms of temperature (41–45 °C), duration, and co-administration of nanoparticles. Results: The most suitable exposure temperature for rat liver appears to be 42 °C, resulting in vacuolar degeneration lesions at the focal level. The effects of thermal conditioning do not appear to be homogeneous in the tested liver, and the controlling environment and methodology should be improved in the near future. The level of hepatic inflammation, as indicated by elevated interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) levels, appears negligible under the current hyperthermia protocol. Conclusions: Two-stage microwave hyperthermia using magnetic nanoparticles is a promising therapeutic modality for liver cancer, with promising results from animal studies opening the way for further research in humans. Full article

Intracerebral hemorrhage (ICH) is a type of stroke with high mortality and disability rates. The hemoglobin and iron ions released by ruptured red blood cells after ICH can induce programmed cell death characterized by lipid peroxide accumulation—a defining feature of ferroptosis—which is one of the key mechanisms for the occurrence and progression of secondary brain injury after ICH. Betaine (BET), a natural amino acid derivative, is known to be an antioxidant, but its protective effect and molecular mechanisms in ICH-induced ferroptosis have not been studied yet. In this study, we investigated the effect of BET intervention on ICH-induced ferroptosis and possible mechanisms in vitro and in vivo, and we evaluated the expression of ferroptosis and oxidative stress molecules through in vivo and in vitro experiments. We analyzed the distribution of nuclear factor E2-related factor 2 (Nrf2) and assessed neurobehavioral function, hematoma volume, and iron content in the brain tissue of mice with ICH. BET upregulates nuclear factor E2-related factor 2/heme oxygenase 1 (Nrf2/HO-1) signaling, reducing long-chain acyl-CoA synthetase 4 (ACSL4), reactive oxygen species (ROS), and malondialdehyde (MDA) while increasing glutathione (GSH) and glutathione peroxidase 4 (GPX4) levels. It also decreases brain iron accumulation, aids hematoma clearance, and protects against ferroptosis and oxidative damage post ICH. Inhibition of Nrf2 with ML385 diminishes BET’s neuroprotective effects, highlighting the pathway’s importance in BET’s mechanism of action. BET boosts antioxidant capacity via the Nrf2/HO-1 pathway; inhibits ferroptosis; reduces oxidative stress, brain edema, and iron accumulation post ICH; and aids hematoma clearance, offering neuroprotection. Full article

Selenium (Se) is an antioxidant essential trace element influencing inflammatory and immune pathways. This systematic review aimed to evaluate the role of maternal Se status during pregnancy in miscarriage risk. A systematic search of PubMed and Embase up to July 2024 was conducted to identify relevant original research studies in English. Available evidence was qualitatively synthesized and predefined sources of bias were assessed. Of 2345 studies identified, 421 full texts were assessed and 14 were included, encompassing 2309 pregnancies. Despite notable methodological limitations across several studies, current evidence indicates that maternal blood Se concentrations are lower among women who experience miscarriage compared to those with uncomplicated pregnancies. Findings regarding placental Se levels were inconsistent, but important methodological issues were noted. Environmental Se exposure was investigated in a single low-powered study, which did not demonstrate a statistically significant association. Potential interactions between Se status, co-exposure to other environmental or lifestyle factors, and effect modification remain insufficiently explored. Adequate maternal Se status during early gestation may reduce miscarriage risk by mitigating oxidative stress and ferroptosis, supporting immune regulation, and modulating thyroid autoimmunity and function. However, causal inference cannot be established due to the absence of randomized interventional evidence. Full article

Purpose: Timeliness of systemic therapy initiation for advanced lung cancer is highly dependent on pathology and molecular pathology laboratory services. Here, we aimed to prospectively evaluate liquid biopsy as a potential strategy to expedite systemic therapy decision-making in lung cancer management. Patients and Methods: This prospective cohort study included consecutive patients with suspected lung cancer seen at the time of initial specialist consultation who underwent both liquid and solid tumour biopsy (group A) and patients with confirmed lung malignancy who underwent solid tumour biopsy alone (group B), between 1 February 2022 and 31 May 2023. Due to laboratory factors, liquid biopsies were processed in batches of 13, whereas solid tumour biopsies were processed individually upon receipt, as per standard practices. Co-primary endpoints included the time from solid versus liquid biopsies to biomarker reporting and palliative systemic therapy initiation. Results: A total of 324 patients were included in the study. The median time from date of blood draw to date of liquid biopsy result was 78 days. For group A (n = 50), the median time from date of solid tumour biopsy to biomarker reporting was 22 days, and the median time from date of solid tumour biopsy to palliative systemic therapy was 42 days. The median time from date of liquid biopsy blood draw to palliative systemic therapy initiation was 56 days. For group B (n = 274), the median times from date of biopsy to biomarker reporting and to palliative systemic therapy initiation in all patients were 22 and 47 days, respectively. Conclusions: While we did not demonstrate improvement in timeliness of biomarker reporting or systemic therapy initiation with liquid biopsy, several barriers leading to delay in liquid biopsy reporting were identified due to unexpected COVID-19-related supply chain disruption and the cost-limiting need to batch sample analysis. Further studies that address the identified barriers are warranted to assess the potential improvement in timeliness of care, should liquid biopsy analysis be implemented in real-time. Full article

Background/Objectives: Vitamin B₁₂ deficiency is increasingly recognized as a contributor in both vascular and neurodegenerative aging-related disorders. Its deficiency disrupts one-carbon metabolism, leading to impaired homocysteine (Hcy) cycling. Elevated Hcy is a well-established risk factor for vascular dysfunction. Previously, we established that elevated Hcy contributes to aging retinal diseases and plays a central role in blood retinal barrier (BRB) dysfunction. Building on this foundation, the present study examines how B-vitamin deficiency disrupts one-carbon metabolism and whether restoring these vitamins can serve as a preventive or therapeutic strategy. Since B-vitamins (B₆, B₉, and B₁₂) are crucial cofactors in the metabolism of Hcy, we investigated how dietary changes in these vitamins affect serum Hcy levels and retinal vascular integrity in mice. Methods: C57BL/6- Wild-type (WT) and cbs^+/− mice (Cystathionine Beta-Synthase heterozygotes, common mouse model for elevated Hcy) were fed specially formulated diets, which contained different levels of B-vitamins (normal, deficient (B-Vit (−)) or enriched (B-Vit (+)). Initially, two groups of mice were placed on either a normal or a deficient diet. After 12–16 weeks, the success of the diet regimes was confirmed by observing serum B₁₂ deficiency in the B-Vit (−) group, along with elevated Hcy levels. Subsequently, a subgroup of the B-Vit (−) mice was switched to an enriched diet. The BRB integrity was evaluated in living mice using fluorescein angiography (FA), optical coherence tomography (OCT), and in the perfused mice retinas with Western blot analysis of leaked retinal albumin and tight junction proteins (occludin and ZO-1) levels. Results: The B-vitamin deficiency caused significant drop in serum vitamin B₁₂ and an increase in plasma Hcy, leading to vascular leakage, altered retinal thickness, choroidal neovascular changes, increased retinal albumin leak, and decreased tight junction protein expression, indicating BRB disruption, which was restored with B-vitamin supplementation. Conclusions: a long-term deficiency of vitamins B₆, B₉, and B₁₂ can lead to disruptions in the BRB. However, supplementation with these B-vitamins has the potential to reverse these effects and help maintain the integrity of BRB. This under-score the significance of one-carbon metabolism for retinal health and suggests that ensuring adequate levels of B-vitamins may aid in preventing aging retinal diseases with BRB disruption such as diabetic retinopathy and age-related macular degeneration. Full article

Background/Objectives: Long-term serological studies are essential to understand how repeated antigenic exposure affects the specific humoral immune response. The aim of this study was to investigate the long-term SARS-CoV-2 antibody dynamics in Austrian blood donors, as representatives of healthy adults, over a period of 36 months after the first SARS-CoV-2 infection. Methods: SARS-CoV-2 anti-N antibody levels were determined in more than 146,000 blood donations collected between 2020 and 2025. In addition, SARS-CoV-2 anti-N and anti-S antibody dynamics were examined in 204 individual blood donors at predefined points in time over a period of 36 months. Reinfections were inferred from increases in anti-N levels within an individual. Vaccination history and self-reported infection data were documented. Results: Anti-N seroprevalence was over 90% from the beginning of 2023 and remained at this level until 2025. Among the longitudinally observed participants, 97% had at least one serologically detected reinfection and 50% had two or more. While anti-N levels continued to increase over time, suggesting cumulative antigenic stimulation, anti-S concentrations and in vitro antibody functionality remained consistently high. Self-reported reinfections underestimated the actual incidence by a factor of six. Symptom profiles shifted toward mild respiratory manifestations, with significantly fewer cases of hyposmia or dysgeusia reported compared to the initial infection. Conclusions: After three years of observation, SARS-CoV-2 immunity is characterized by sustained antibody activity. The results show a transition from persistent, but inherently declining, to a repeatedly rebuilding, enhanced humoral immunity, indicating that SARS-CoV-2 has become endemic in Austria. Full article

Red blood cells (RBCs) are essential for transporting oxygen from lungs to peripheral tissues. However, the impact of transmissible gastroenteritis virus (TGEV) infection on RBCs and its potential pathophysiological significance during disease progression remain largely unexplored. In this study, hematological analysis of TGEV-infected piglets revealed significant reduction in both RBC distribution width–coefficient of variation and RBC distribution width–standard deviation, alongside elevated pCO₂ levels. Viral detection confirmed the presence of TGEV within RBCs from infected piglets. Further investigation demonstrated that TGEV could bind to, but not replicate in, RBCs. TGEV-bound RBCs exhibited crenated and impaired deformability, which were associated with reduced oxygen-carrying capacity. Additionally, TGEV infection promoted macrophage-mediated phagocytosis of RBCs and led to decreased serum iron levels, factors that might enhance TGEV infection. Collectively, these results demonstrated the involvement of RBCs in the progression of TGEV infection, providing new insights for the development of diagnostic and therapeutic strategies. Full article

This literature review examined the relationship between energy drink consumption and cardiovascular health in young people. Following PRISMA 2020, we searched Scopus for articles published from 2020 to 2025 and included 33 original studies after screening 133 records. Evidence from observational, clinical, and experimental research was synthesized into six themes: youth consumption; direct cardiovascular outcomes; composition and toxicity; animal or cellular experiments; perceptions and habits; and occupational or sociodemographic factors. Across studies, habitual intake was linked to acute blood-pressure rises, arrhythmias, endothelial dysfunction, and metabolic disturbances, sometimes within 24 h of a single can. Risks were amplified by high caffeine and taurine doses and by co-use with alcohol or intense exercise. Adolescents and young adults were most vulnerable, due to heightened sympathetic responses, frequent use under academic or work stress, and limited risk perception. Authors highlighted five actions: longitudinal research; tighter ingredient monitoring and transparent labeling; consumer education; protection of vulnerable groups; and clinical guidance for responsible use. These results were observed across regions and study designs. Overall, the findings indicate that unregulated energy-drink consumption is a preventable cardiovascular risk in youth, justifying the use of coordinated public-health measures, including curriculum-based education, marketing restrictions, ingredient oversight, and clinical screening to mitigate harm. Full article

Although best known as a major parasite of sheep and goats, the blood-feeding abomasal nematode Haemonchus contortus can also infect cattle and buffaloes under the mixed-grazing Mediterranean conditions prevalent in Greece. The objectives of this study were as follows: (i) to determine the prevalence of H. contortus infections in dairy and beef cattle and buffaloes in Greece through an abattoir survey, (ii) to evaluate potential host- and farm-related risk factors including age, sex, management system, cattle productive orientation, and the co-existence of cattle and buffaloes on the occurrence of haemonchosis, and (iii) to assess the likelihood of detecting homozygous benzimidazole (BZ)-resistant H. contortus in large ruminant populations in relation to these determinants. A total of 213 abomasa (115, 55, and 43 from dairy, beef cattle, and buffaloes, respectively) were examined. A structured questionnaire provided additional animal- and farm-level information. Haemonchus-like helminths were collected and molecularly identified at the species level by amplifying a 321 bp fragment of the internal transcribed spacer 2 region of nuclear DNA. An allele-specific multiplex PCR, targeting codon 200 of the β-tubulin gene, was applied to detect BZ-resistant alleles. The prevalence of H. contortus infection was 21.2% in cattle and 69.8% in buffaloes. In cattle, multivariable analysis revealed that mixed-species farming (i.e., farms where cattle were the primary species and buffaloes were kept in smaller numbers), productive orientation, and slaughter age were significant predictors of increased H. contortus infection. Controversially, none of these factors were significantly associated with infection in buffaloes. Finally, multivariable modelling suggested that resistance patterns varied by host species, being more prevalent in intensively managed, older cattle, yet less common among older buffaloes and in herds where both species coexisted. Full article

High-altitude exposure poses significant health challenges to mountaineers, military personnel, travelers, and indigenous residents. Altitude-related illnesses encompass acute conditions such as acute mountain sickness (AMS), high-altitude pulmonary edema (HAPE), and high-altitude cerebral edema (HACE), and chronic manifestations like chronic mountain sickness (CMS). Hypobaric hypoxia induces oxidative stress and inflammatory cascades, causing alterations in multiple organ systems through co-related amplification mechanisms. Therefore, this review aims to systematically discuss the injury mechanisms and comprehensive intervention strategies involved in high-altitude diseases. In summary, these pathologies involve key damage pathways: oxidative stress activates inflammatory pathways through NF-κB and NOD-like receptor thermal protein domain-associated protein 3 (NLRP3) inflammasomes; energy depletion impairs calcium homeostasis, leading to cellular calcium overload; mitochondrial dysfunction amplifies injury through mitochondrial permeability transition pore (mPTP) opening and apoptotic factor release. These mechanisms could be converged in organ-specific patterns—blood–brain barrier disruption in HACE, stress failure in HAPE, and right heart dysfunction in chronic exposure. Promising strategies include multi-level therapeutic approaches targeting oxygenation (supplemental oxygen, acetazolamide), specific pathway modulation (antioxidants, calcium channel blockers, HIF-1α regulators), and damage repair (glucocorticoids). Notably, functional foods show significant therapeutic potential: dietary nitrates (beetroot) enhance oxygen delivery, tea polyphenols and anthocyanins (black goji berry) provide antioxidant effects, and traditional herbal bioactives (astragaloside, ginsenosides) offer multi-targeted organ protection. Full article

Cattle tick fever (CTF), caused by Anaplasma marginale, Babesia bovis and Babesia bigemina, remains a sanitary and economic challenge for cattle farming in Brazil. Thus, this study evaluated the prevalence, regional distribution, co-infection patterns, and risk factors associated with CTF causative agents in cattle the semi-arid region of Paraíba, the semi-arid region of Ceará, and the Tropical Humid region of Paraíba, Northeast Brazil. Blood samples were collected from 336 cattle, from 60 farms, and analyzed by means of conventional PCR and nested-PCR, while epidemiological data were obtained through questionnaires applied to producers. The overall infection prevalence by at least one pathogen was 82.7% (278/336), with higher rates in the tropical humid region of Paraíba at 94.8% (109/115), followed by the semi-arid region of Ceará, with 88.1% (89/101) and the semi-arid region of Paraíba with 66.6% (80/120). Co-infections were frequent, especially the association between A. marginale and B. bigemina, detected in 23.2% (78/336) of the animals, while triple infections occurred in 15.8% (53/336) and were most frequent in the semi-arid region of Ceará at 21.8% (22/101). The semi-arid region of Paraíba had the fewest entirely positive properties (7/20) and the highest number of entirely negative properties (2/20). The tropical humid region of Paraíba had the highest number of entirely positive properties (17/21), with no properties entirely free of CTF agents. Multivariate analysis identified the presence of horn fly (OR = 7.23; CI 3.05–18.86; 95% CI), needle reuse (OR = 5.8; CI: 2.62–13.90; 95% CI), animal purchase and introduction without quarantine (OR = 5.4; CI: 2.17–14.93; 95% CI), and pasture sharing (OR = 3.21; CI: 1.08–11.25; 95% CI) as risk factors, while beef herds showed lower susceptibility (OR = 0.28; CI: 0.15–0.52; 95% CI). These findings demonstrate that infections by CTF causative agents are endemic but exhibit region-specific epidemiological patterns, reflecting the combined effects of climate and management practices, and localized transmission foci that may be intensified by commercial cattle movement. Full article

Background/Objectives: COVID-19 and long COVID remain prevalent, with household transmission being an important mode of spread. To quantify household transmission of subclinical SARS-COV-2 infection and identify sociodemographic risk factors that may explain disparities in transmission, we conducted a case-ascertained antibody surveillance study of households in Cincinnati, Ohio. Methods: A partnership was formed between the Cincinnati Health Department and Cincinnati Children’s Hospital Medical Center. The Health Department identified cases of COVID-19. Infected individuals, along with their household contacts (n = 245), completed multiple questionnaires about symptoms, demographics, psychosocial (Adverse Childhood Experiences Scale and Everyday Discrimination Scale) and social risk factors, and conditions before and during the pandemic. In addition, they completed a non-fasting blood draw for IgG, IgM, IgA, and nucleocapsid protein serology testing. Results: Household contacts experienced few symptoms of COVID-19. However, according to the presence of the nucleocapsid protein, nearly 50% contracted the SARS-CoV-2 virus. This rate was similar by vaccination status but it was higher for household contacts who experienced high levels of early life adversity compared with those with lower levels. Conclusions: Our results confirm the high transmission of subclinical disease among household contacts, which may vary due to psychosocial factors. This reinforces the importance of isolating cases to prevent transmission, regardless of vaccination status. Full article

Equine bacterial abortion presents substantial economic and One Health challenges; however, comprehensive epidemiological data from China are limited. This study sought to ascertain the overall prevalence of key pathogens—namely, Chlamydia spp., Coxiella burnetii, Salmonella abortus equi, and Brucella spp.—in equine populations in northwestern China. In this study, we aimed to further elucidate the characteristics of co-infections, profile antimicrobial resistance genes, and identify associated risk factors. Conducted as a cross-sectional analysis across four provinces, we collected 508 blood samples and 24 abortion tissue samples from 15 farms. Pathogen detection was performed using ELISA and real-time PCR, complemented by a targeted PCR panel screening for 29 AMR genes. The highest prevalence was observed for S. abortus equi (serology: 35.03%; molecular: 23.03%), followed by C. burnetii (28.94%; 15.35%) and Chlamydia spp. (18.90%; 14.17%). No PCR-confirmed cases of Brucella spp. were detected, despite low-level seropositivity. Notably, donkeys and horses aged 5–10 years exhibited higher positivity rates, and co-infections were common, particularly S. abortus equi + C. burnetii (n = 44). Among the 196 PCR-positive samples, extended-spectrum beta-lactamase (ESBL) genes were predominant, with CTX-M (n = 158) and TEM-1 (n = 106) being the most prevalent. Additionally, we identified a high prevalence of genes conferring resistance to fluoroquinolones (qnrA/B), tetracyclines (tetM), macrolides (ermA/B/C), and sulfonamides (sul1), along with sporadic occurrences of carbapenemase genes. This study presents the inaugural comprehensive analysis of pathogen prevalence and associated antimicrobial resistance (AMR) gene carriage in equine abortion cases in northwest China. The findings highlight the imperative for integrated serological and molecular surveillance, revealing a significant discrepancy between empirical therapeutic approaches and the prevalent resistance genotypes. Consequently, this research lays the groundwork for evidence-based biosecurity measures and antimicrobial stewardship within a One Health framework. Full article