Search Results (3,313)

Heart failure (HF), particularly of an ischemic etiology, is steadily increasing worldwide. Non-anemic iron deficiency (ID) is highly prevalent among HF patients, and it has been related to worse outcomes. Growth differentiation factor 15 (GDF15) has been related to atherosclerotic cardiovascular (CV) disease, HF and iron pathophysiology. Nevertheless, the specific potential role of GDF15 in HF patients with ID has not been fully explored. In this cross-sectional study we determined serum GDF15 levels in 60 HF patients with ID from the IRON-PATH II study. The discriminative capacity of GDF15 in logistic regression models for classifying these patients according to ischemic etiology was defined as the primary endpoint. Additionally, relationships between GDF15 levels and impaired right ventricle function, impaired functional capacity and HF were included as secondary endpoints. GDF15 was inversely related to tricuspid annular plane systolic excursion (TAPSE) and the six-minute walking test (6MWT), and positively related to hallmarks of HF [i.e., N-terminal prohormone of brain natriuretic peptide (NT-proBNP)] and other molecules influenced by HF progression [i.e., creatinine and ferritin]. Moreover, GDF15 was inversely related to hemoglobin, suggesting a potential link to iron homeostasis. Furthermore, GDF15 showed good classification capacity and improved the accuracy of a logistic regression model for ischemic HF classification in patients with ID. Overall, the findings of this study propose serum GDF15 levels as a potential tool for the classification of HF patients with ID according to the ischemic etiology. Full article

Congenital heart disease (CHD), the most prevalent congenital abnormality, is becoming increasingly acknowledged as a component of a broad fetoplacental pathology. This systematic review summarizes recent imaging-based data linking CHD to quantifiable placental abnormalities. In CHD pregnancies, placenta studies consistently show patterns of altered vascularization, decreased volumetric growth, microstructural heterogeneity, and impaired placental oxygenation. We conducted a thorough literature search from January 2020 to May 2025 to identify studies on placenta function and structure in CHD-affected pregnancies. The included studies primarily utilized MRI and Doppler methods, as well as some modern modalities. Seven studies were included in this review. Placental imaging reveals consistent structural and functional abnormalities in pregnancies affected by congenital heart disease, indicating some possible contribution of the placenta in CHD pathophysiology. Placental imaging may improve outcomes in this susceptible group of pregnancies, improve risk assessment, and direct surveillance when incorporated into prenatal care for congenital heart disease. Future research should concentrate on lesion-specific analysis, longitudinal imaging, and placenta–heart axis-targeting treatment therapies. Full article

This study investigated individual/combined nitrogen (N) and potassium (K) deficiencies on ginseng root aroma using GC–MS metabolomics. Four treatments (normal supply, N deficiency (LN), K deficiency (LK), and dual deficiency (LNLK)) were analyzed. Deficiencies impaired growth, mineral accumulation, and induced oxidative stress, suppressing ginsenoside biosynthesis. From 1768 detected VOCs, 304 compounds (rOAV ≥ 1) significantly contributed to aroma. LN inhibited terpenoids (e.g., isoborneol) but upregulated sulfur compounds (e.g., di-2-propenyl tetrasulfide), intensifying pungency. LK enhanced sweet/woody notes (e.g., 2′-acetonaphthone) via flavonoid biosynthesis and toluene degradation. LNLK reduced esters (e.g., benzyl acetate) and terpenes, attenuating floral–balsamic nuances by coordinating aromatic degradation, glutathione metabolism, and ABC transporters. N–K nutrition dynamically shapes ginseng aroma by differentially regulating phenylpropanoid, terpenoid, and sulfur pathways, providing a foundation for precision fertilization and quality improvement. Full article

Oxidative stress, defined as the imbalance between reactive oxygen species (ROS) and antioxidant defenses, plays a pivotal role in the pathogenesis of several pregnancy complications, notably preeclampsia (PE), gestational diabetes mellitus (GDM), fetal growth restriction (FGR), and recurrent pregnancy loss (RPL). During normal pregnancy, low to moderate ROS levels support essential placental functions such as angiogenesis and trophoblast differentiation. However, excessive ROS production overwhelms antioxidant systems, leading to lipid peroxidation, protein and DNA damage, and impaired placental function. This review synthesizes current evidence linking oxidative stress to adverse pregnancy outcomes, highlighting key biomarkers such as malondialdehyde (MDA), 8-hydroxy-2′-deoxyguanosine (8-OHdG), and 8-iso-prostaglandin F2α (8-iso-PGF2α). While antioxidant therapies—particularly vitamins C and E, selenium, and folic acid—have shown promise in reducing oxidative markers, their impact on clinical outcomes remains inconsistent. The variability in results underscores the need for standardized biomarker protocols and personalized treatment strategies based on genetic predispositions and baseline oxidative status. Future research may better harness antioxidant interventions to improve maternal–fetal health by addressing these gaps. Full article

Thermo-tolerance is a virulence factor responsible for the emergence of new fungal pathogens, including Candidozyma auris (formerly classified as Candida auris, C. auris). It has been shown that in C. auris the thermo-tolerance, as well as other virulence traits, such as the ability to aggregate, to form pseudo-hyphae, or to produce melanin are strain-specific features. Here, we investigated the impact of different temperatures (25 °C, 37 °C and 42 °C) on the phenotypic and virulence profile of C. auris strain CDC B11903. The results show a positive correlation between the resistance to antifungals and increasing temperature from 25 °C to 37 °C, while no differences were observed between 37 °C and 42 °C, except for Anidulafungin. Furthermore, C. auris growth was impaired at 25 °C as compared to 37 °C and 42 °C. Except for the haemolytic activity, which increased with rising temperatures, phospholipase, lipase and biofilm production were found at all tested temperatures. Moreover, the ability to produce melanin was observed only at 37 °C and 42 °C. The capacity to grow as pseudo-hyphae or in clusters and to adhere to both biotic and abiotic surfaces were observed at all the temperatures tested, with increased propensity of C. auris to adhere to abiotic surfaces with rising temperatures. The results underline the thermo-tolerance of C. auris strain B11903 and its increased virulence profile at human body temperature both in physiological (37 °C) and febrile state (42 °C). Full article

Gestational diabetes mellitus (GDM), a prevalent metabolic disorder in pregnancy, induces maternal hyperglycemia and elevates fetal malformation risks, particularly in craniofacial development. To investigate the underlying mechanisms, we employed zebrafish as a model organism due to its conserved skeletal development pathways with humans. Zebrafish embryos were exposed to 3.5% and 4% high glucose (HG) from 10–80 h post-fertilization (hpf). Through comprehensive analyses including Alcian blue staining, confocal microscopy, and molecular assays, we demonstrated that HG exposure caused significant developmental abnormalities including growth retardation, craniofacial cartilage malformations, and impaired cranial neural crest cells (CNCCs) migration and proliferation. Mechanistically, HG induced reactive oxygen species (ROS) accumulation and oxidative stress while downregulating critical CNCCs markers (dlx2 and tfap2a). These molecular alterations correlated with histomorphological defects in pharyngeal arch cartilage, particularly in ceratohyal formation. Our findings establish that glucose disrupts craniofacial development through oxidative stress-mediated CNCCs dysfunction, providing novel mechanistic insights into GDM-associated skeletal abnormalities and potential therapeutic targets. Full article

Background: Epithelial-mesenchymal transition (EMT) is prevalent in human cancer and facilitates tumor metastasis and therapy resistance by enhancing cancer cell motility, invasiveness, survival, and immune evasion. However, the molecular mechanisms underlying the cellular changes during EMT remain largely elusive, making it challenging to simultaneously target these diverse malignant phenotypes. Results: Here, we show that the EMT-inducing ZEB transcription factors directly repressed WWC1 (also known as KIBRA), a key upstream activating component of the Hippo signaling pathway. The EMT program thus inherently downregulated WWC1, leading to impaired Hippo signaling and constitutive activation of the downstream effector and transcriptional coactivator YAP. The YAP-dependent transcriptional program promotes manifold cellular phenotypes that resemble those induced during EMT. Indeed, pharmacological inhibition of YAP suppressed EMT-stimulated cell migration and invasion, apoptosis resistance, and cell size growth, identifying active YAP as a common essential mediator of multiple EMT-associated phenotypes. Moreover, YAP activation directly induced transcription of B7 family immune checkpoint proteins VSIR (VISTA) and PD-L2, and rendered cancer cells resistant to effector CD8 T cells. Conclusions: Collectively, the results suggest that EMT intrinsically activates YAP by repressing WWC1, providing a non-genetic mechanism for pervasive YAP activation in cancer. Activated YAP, in turn, critically contributes to diverse EMT-enhanced malignant phenotypes and immune evasion. Therefore, pharmacological targeting of YAP may suppress various EMT-associated malignant properties and improve the efficacy of anti-PD-1 immunotherapy, offering a promising therapeutic strategy against cancer cells exhibiting EMT characteristics. Full article

The performance of lettuce, pepper, and chili pepper, and the biological soil quality, in a ground-mounted PV system under cultivation conditions typical of the Mediterranean environment of the Puglia region were evaluated. Microclimatic parameters, plant growth and yield response, soil quality assessed using the QBS-ar index, and land equivalent ratio (LER) were determined in three different cultivation areas: a cultivation area outside the photovoltaic plant but immediately adjacent to it (‘Control’); the inter-row area closest to the row of panels exposed to sunlight (‘Area close PV structure’); the inter-row area distant from the row of panels (‘Area distant PV structure’). Cumulated solar radiation, in particular during the summer growing cycles, was only slightly affected in the Area distant PV structure (1616 and 2130 MJ m⁻² for pepper and chili pepper, respectively, in the control area, in comparison to 1630 and 2044 MJ m⁻², in the Area distant PV structure), while it was strongly reduced in the Area close PV structure (883 and 1091 MJ m⁻² for pepper and chili pepper, respectively). In general, a reduction in air temperature and wind speed, as well as an increase in relative air humidity, was observed under PV conditions. On average, the evapotranspirative demand was reduced in the PV growing conditions compared to open field, with a more relevant effect in the sub-zone close to the photovoltaic structures, where cumulative ET0 was 28% and 34% lower than the Control in the pepper and chili pepper growing cycle, respectively. Lettuce growth was impaired by PV cultivation conditions, with an average reduction of 15% in plant height and 37% in marketable yield per plant, with no significant differences between the two sub-zones in the PV system. For pepper, the best growing conditions were observed in open field control compared to PV, but with differences related to the PV sub-zone. The plants grown in the Area distant PV structure were more negatively affected by the modified growing conditions, showing the lowest shoot and fruit fresh weight, the latter reduced by 51% compared to the Control; intermediate values were observed for these parameters in the Area close PV structure, with a less severe tendency to yield reduction. For chili pepper, both shoot and fruit fresh weight were lower in PV conditions, regardless of the sub-zone, with a reduction of 82% in yield per plant compared to the Control. However, despite the yield reductions, the LER was improved (1.60 and 1.40 in case of a lettuce + pepper or lettuce + chili pepper annual cropping program, respectively), highlighting a more efficient use of land, without negative or even ameliorative impacts on biological soil quality and biodiversity in terms of QBS-ar and microarthropods taxa abundance. Knowledge of the response of different crops under cultivation conditions typical of specific environments is necessary to define optimal cropping programs aimed at maximizing resource-use efficiency and land use. Full article

Poultry production exposes birds to diverse environmental and physiological stressors that disrupt redox balance, impair gut–liver axis function, and undermine health and productivity. This study investigated the hepatoprotective and antioxidative effects of mangosteen pericarp extract (MPE) in an experimental model of diquat-induced oxidative stress in laying hens. A total of 270 Hy-Line White laying hens were randomly assigned to three groups: control group (CON), diquat-challenged group (DQ), and MEP intervention with diquat-challenged group (MQ), with six replicates of 15 birds each. The results showed that MPE supplementation effectively mitigated the hepatic oxidative damage caused by diquat, as evidenced by the increased ALT and AST activity, improved lipid metabolism, and reduced hepatic fibrosis. Mechanistically, MPE activated the NRF2/HO-1 antioxidant pathway, thus enhancing the liver’s ability to counteract ROS-induced damage and reducing lipid droplet accumulation in liver tissue. MPE supplementation restored intestinal barrier integrity by upregulating tight junction protein expression (Occludin-1 and ZO-1), enhancing MUC-2 expression, and thereby decreasing gut microbiota-derived LPS transferring from the intestine. Additionally, MPE also modulated gut microbiota composition by enriching beneficial bacterial genera such as Lactobacillus and Ruminococcus while suppressing the growth of potentially harmful taxa (e.g., Bacteroidales and UCG-010). Fecal microbiota transplantation (FMT) from MPE-treated donors into diquat-exposed recipients reproduced these beneficial effects, further highlighting the role of gut microbiota modulation in mediating MPE’s systemic protective actions. Together, these findings demonstrated that MPE alleviated DQ-induced liver injury and oxidative stress through a combination of antioxidant activity, protection of intestinal barrier function, and modulation of gut microbiota, positioning MPE as a promising natural strategy for mitigating oxidative stress-related liver damage by regulating the gut microbiota and gut–liver axis in poultry. Full article

Background/Objectives: Toxoplasma gondii, an obligate intracellular parasite, poses a major global health concern owing to its potential for congenital transmission, particularly during pregnancy. Current pharmacological treatments, including spiramycin and pyrimethamine, exhibit limitations in both efficacy and safety, underscoring the need for novel therapeutic strategies. In this study, we investigated the antiparasitic potential of BthTX-II, an Asp49 phospholipase A₂ (PLA₂) isolated from Bothrops jararacussu venom, in human trophoblast cells (BeWo) and third-trimester human placental explants infected with T. gondii. Methods: In vitro assays were performed using BeWo cells infected with T. gondii tachyzoites and treated with non-cytotoxic concentrations of BthTX-II (3.125, 1.56, and 0.78 µg/mL). An ex vivo model employing third-trimester human placental villous explants was used under similar conditions. Parasite proliferation, adhesion, and invasion were assessed alongside host immune response modulation. Results: Our findings demonstrate that BthTX-II reduces T. gondii proliferation in BeWo cells at all tested non-cytotoxic concentrations. The toxin also significantly impaired parasite adhesion and invasion while modulating host immune response by upregulating interleukin (IL)-6, IL-8, and macrophage migration inhibitory factor (MIF), and downregulating vascular endothelial growth factor—potentially disrupting parasite proliferation. In placental villous explants, BthTX-II (1.56 μg/mL) reduced T. gondii proliferation and modulated IL-8, MIF, and tumour necrosis factor-alpha levels without compromising tissue viability. Conclusions: These findings highlight BthTX-II as a potential candidate in toxoplasmosis treatment. Further investigation should focus on its dual role in limiting parasite development and modulating immune responses at the maternal–fetal interface. Full article

Intrauterine growth restriction (IUGR) severely hinders the development of the livestock industry and impacts economic efficiency. MicroRNAs (miRNAs) participate in the epigenetic regulation of animal growth and development. Using IUGR pigs as a model, this study analyzed transcriptomic data from IUGR piglets to investigate the miRNA-mRNA regulatory network in their testes. Compared with NBW pigs, IUGR pigs exhibited reduced testicular volume, decreased weight, and abnormal testicular development. A total of 4945 differentially expressed mRNAs and 53 differentially expressed miRNAs were identified in IUGR testicular tissues, including 1748 downregulated and 3197 upregulated mRNAs, as well as 41 upregulated and 12 downregulated miRNAs. The integrated analysis of differentially expressed genes, miRNA target genes, and the miRNA-mRNA network revealed that IUGR may impair testicular development by disrupting cell cycle progression and apoptotic pathways, thereby hindering normal testicular cell growth. Furthermore, analysis of the miRNA-mRNA network indicated that miRNAs such as ssc-miR-23a, ssc-miR-29c, ssc-miR-193a-3p, and ssc-miR-574-3p could serve as potential marker miRNAs for IUGR testes, while YWHAZ, YWHAB, and PPP2CA may function as core target genes within this regulatory network. In conclusion, this study enhances our understanding of male reproduction in IUGR pigs and provides a theoretical foundation for preventing and treating IUGR-induced male reproductive disorders. Full article

Objective: This study investigated the association between paternal preconception paternal body mass index (BMI) categories and physical/neurodevelopmental outcomes in Chinese small-for-gestational-age (SGA) children. Methods: A prospective cohort study enrolled 412 singleton SGA infants born at Peking University People’s Hospital in 2020–2022. Fathers were stratified into underweight, normal-weight, overweight, and obese groups. Follow-up assessments at 24–36 months evaluated growth parameters weight, height, BMI Z-scores and neurodevelopment using the Ages and Stages Questionnaire-3 (ASQ-3) and ASQ: Social–Emotional (ASQ:SE). Multivariable regression was adjusted for paternal covariates. Results: In SGA offspring, paternal underweight correlated with lower birth weights vs. normal/obese paternal BMI and the highest severe SGA rates. Prospective monitoring identified elevated BMI Z-scores (ΔZ = +0.40) and 8.7-fold heightened obesity risk in the paternal obesity group versus normal-weight counterparts. Neurodevelopmental evaluations demonstrated gross motor impairments in both underweight (ΔZ = −0.22) and obese paternal subgroups (ΔZ = −0.25) compared with the normal-weight group, with the obesity cohort additionally exhibiting problem-solving deficiencies (ΔZ = −0.19). The paternal obesity group manifested three-fold greater likelihood of social–emotional delays than the normal-weight group. The underweight and obese paternal groups showed 3.46-fold and 2.73-fold higher probabilities of gross motor deficits, respectively, while obesity was linked to 3.27-fold elevated problem-solving impairment risk-all comparisons versus normal paternal BMI. Overweight status showed no significant links to growth or neurodevelopmental outcomes. Normal-weight fathers had lower risks of obesity and neurodevelopmental issues. Conclusions: This study revealed U-shaped paternal BMI–neurodevelopment links in SGA offspring. Paternal obesity raised offspring obesity/neurodevelopmental risks, while underweight linked to severe SGA and motor deficits, highlighting paternal weight optimization’s modifiable role. Full article

Saline–alkaline water resources are globally widespread, and their rational development offers significant potential to alleviate freshwater scarcity. Saline–alkaline water aquaculture farming not only affects fish growth and survival but also impairs reproductive and developmental functions. Largemouth bass (Micropterus salmoides), an economically important fish, has demonstrated excellent high tolerance to such environments, in order to investigate the effects of alkaline water aquaculture environments on its growth performance, sex hormone levels, gonadal development, and molecular adaptation mechanisms. In this study, largemouth bass were chronically exposed to freshwater (0.55 mmol/L), low alkalinity (10 mmol/L), or high alkalinity (25 mmol/L) and cultured for 80 days. Alkalinity exposure more severely impacted the growth rate of females. High alkalinity significantly increased the hepatosomatic index and decreased the gonadosomatic index in both sexes; moreover, it induced oxidative stress in both sexes, evidenced by reduced superoxide dismutase (SOD), catalase (CAT), and total antioxidant capacity (TAOC) levels and elevated malondialdehyde (MDA) content. Furthermore, the levels of sex hormones Serum estradiol (E2), 11-ketotestosterone (11-KT), and testosterone were significantly reduced, accompanied by either an elevated ratio of primary oocytes and follicular atresia, or by reduced spermatogenesis. Apoptotic signals appeared in gonadal interstitial cells, with upregulated expression of genes P53, Bax, Casp3, and Casp8. Ultrastructural damage included fewer mitochondria and cristae blurring, further indicating tissue damage causing dysfunction. Transcriptome results showed that oxidative stress damage and energy metabolism imbalance caused by carbonate alkalinity were key to the delayed gonadal development, which was mainly manifested in enrichment of the ECM–receptor interaction and PI3K-Akt signaling pathways in females exposed to low alkalinity, and the GnRH secretion and chemokine signaling pathways in males. Glycosphingolipid biosynthesis and Ferroptosis pathway were enriched in females exposed to high alkalinity, and the Cortisol synthesis and secretion pathway were enriched in males. Overall, high-alkalinity exposure significantly delayed gonadal development in both sexes of largemouth bass, leading to reproductive impairment. Full article

Despite notable progress in cancer therapy, immune evasion remains a major obstacle to effective treatment outcomes. In the context of spaceflight, astronauts are exposed to unique environmental stressors—particularly microgravity and radiation—that profoundly affect cellular and immune homeostasis. Emerging evidence suggests that microgravity alters key cellular processes, including proliferation, apoptosis, adhesion, and oncogenic signaling pathways such as NF-κB and ERK1/2. Concurrently, microgravity (µg) disrupts immune regulation, potentially facilitating both tumor progression and treatment resistance. Of particular concern is the upregulation of human endogenous retroviruses (HERVs), especially HERV-K and HERV-W, under µg conditions, which may exacerbate inflammatory responses and immune system dysregulation. While some studies indicate that µg may impair tumor growth, others reveal enhanced immune evasion and reduced antitumor immunity. Importantly, insights from µg research extend beyond space medicine and provide translational opportunities for terrestrial oncology, including the development of physiologically relevant 3D tumor models for drug screening, the identification of mechano-sensitive pathways (FAK/RhoA, YAP/TAZ) as therapeutic targets, and novel immunotherapeutic strategies involving epigenetic modulation and checkpoint inhibition. This review critically examines the dual role of µg in modulating cancer progression and immune function. We synthesize findings on how µg shapes immune responses, alters tumor–immune system interactions, and impacts the efficacy of immunotherapeutic approaches. Finally, we highlight translational opportunities and challenges for optimizing cancer immunotherapy and precision oncology in both spaceflight and Earth-based environments. Full article

The tomato leafminer (Tuta absoluta) is a globally invasive pest that causes severe yield losses in tomato crops. Nanotechnology-based strategies offer promising alternatives to conventional insecticides. This study examines the physiological, biochemical, and demographic responses of T. absoluta following exposure to mesoporous silica nanoparticles (MSNs) applied to tomato leaves at concentrations of 0, 3, 30, and 300 mg L⁻¹. Comprehensive assessments were conducted, including digestive and detoxifying enzyme activities in the insect, neurotoxicity indicators, life table parameters, and antioxidant responses in the host plant. At 30 mg L⁻¹, MSNs significantly impaired larval development, fecundity, and survival of T. absoluta without inducing phytotoxicity. Tomato plants treated at this concentration exhibited enhanced antioxidant enzyme activity (SOD, CAT, POD) and a reduced malondialdehyde (MDA) content, indicating an active oxidative defense. These plant responses were significantly correlated with changes in insect fitness traits, suggesting a plant-mediated effect on pest physiology. Digestive enzyme disruption, decreased acetylcholinesterase activity, and extended developmental periods contributed to suppressed population growth, as evidenced by reductions in the intrinsic rate of increase (r), net reproductive rate (R₀), and fecundity. At 300 mg L⁻¹, however, severe phytotoxicity and enzymatic collapse were observed in both plant and insect systems. These findings highlight moderate concentration of MSNs (30 mg L⁻¹) as a promising dose for sustainable and host-safe pest management, offering multi-targeted suppression of T. absoluta through combined plant and insect biochemical pathways. Full article