Search Results (252)

Ischemic stroke is a serious disease that frequently occurs in the elderly and is characterized by a complex pathophysiology and a limited number of effective therapeutic agents. Salvianolic acid A (SAL-A) is a natural product derived from the rhizome of Salvia miltiorrhiza, which possesses diverse pharmacological activities. This study aims to investigate the effect and mechanisms of SAL-A in inhibiting ferroptosis to improve ischemic stroke. Brain injury, oxidative stress and ferroptosis-related analysis were performed to evaluate the effect of SAL-A on ischemic stroke in photochemical induction of stroke (PTS) in mice. Lipid peroxidation levels, antioxidant protein levels, tissue iron content, nuclear factor erythroid 2-related factor 2 (Nrf2), and mitochondrial morphology changes were detected to explore its mechanism. SAL-A significantly attenuated brain injury, reduced malondialdehyde (MDA) and long-chain acyl-CoA synthase 4 (ACSL4) levels. In addition, SAL-A also amplified the antioxidative properties of glutathione (GSH) when under glutathione peroxidase 4 (GPX4), and the reduction in ferrous ion levels. In vitro, brain microvascular endothelial cells (b.End.3) exposed to oxygen-glucose deprivation/reoxygenation (OGD/R) were used to investigate whether the anti-stroke mechanism of SAL-A is related to Nrf2. Following OGD/R, ML385 (Nrf2 inhibitor) prevents SAL-A from inhibiting oxidative stress, ferroptosis, and mitochondrial dysfunction in b.End.3 cells. In conclusion, SAL-A inhibits ferroptosis to ameliorate ischemic brain injury, and this effect is mediated through Nrf2. Full article

Many contemporaries considered the crusader conquest of Jerusalem in 1099 as a significant moment in Salvation History. This article investigates how the reception of the Roman conquest of the city (70 CE) contributed to such an understanding. The important Benedictine exegete Rupert of Deutz (c. 1070–1129) refers to the Roman conquest in 79 passages within his opus, notably in his various biblical commentaries. This case study shows how the past event provided a rationale, exegetical and providential in nature, to understand three dimensions: (a) the role of the Jews, especially that it had been necessary to deprive them of the Holy Land; (b) the current situation of and purpose of Christians in the Holy Land; and (c) the End of Time, which was expected in Jerusalem, and which Rupert anchored already significantly in his own present. His commentary on John’s Revelation even asserted that the Roman conquest had opened the sixth of seven seals (Rev. 6:12). Therefore, the Apocalypse had been ongoing since 70 CE—but only in the Holy Land, a fact that made it necessary for Christians to travel there. The article thus demonstrates that biblical commentaries are potent sources for both crusade studies and historical research in general. Full article

Sleep deprivation impairs immune function, and melatonin has emerged as a key mediator in this process. This narrative review analyzes 50 studies published between 2000 and 2025 to determine the extent to which reduced melatonin synthesis contributes to immune dysregulation. Consistent sleep loss lowers melatonin levels, which correlates with elevated proinflammatory cytokines (e.g., IL-6 and TNF-α), increased oxidative stress, and reduced immune cell activity, including that of natural killer (NK) cells and CD4+ lymphocytes. Melatonin regulates immune pathways, including NF-κB signaling. It also supports mitochondrial health and helps maintain gut barrier integrity. These effects are particularly relevant in vulnerable populations, including older adults and shift workers. Experimental findings also highlight melatonin’s therapeutic potential in infections like SARS-CoV-2, where it modulates inflammatory responses and viral entry mechanisms. Despite the heterogeneity of study methodologies, a consistent correlation emerges between circadian disruption, melatonin suppression, and immune imbalance. These findings underscore melatonin’s dual role as a chronobiotic and immunomodulator. Addressing sleep loss and considering melatonin-based interventions may help restore immune homeostasis. More clinical trials are needed to determine the best dosing, long-term efficacy, and population-specific strategies for supplementation. Promoting healthy sleep is crucial for preventing chronic inflammation and diseases associated with immune dysfunction. Full article

Light variability is a key environmental stressor influencing the physiology and productivity of marine macroalgae. This study examined the ecophysiological and biochemical responses of Lessonia spicata (Ochrophyta) during a natural light deprivation event caused by a solar eclipse. We measured the in vivo chlorophyll a (Chla) fluorescence, photoinhibition, and photosynthetic capacity, along with the pigment content, phenolic compound accumulation, and antioxidant capacity, to evaluate short-term photosynthetic adjustments. Dark-adapted conditions during the eclipse peak led to reduced photosynthetic and biochemical activity, while post-eclipse recovery involved the increased accumulation of photosynthetic pigments and photoprotective compounds. Carotenoids showed high antioxidant potential under eclipse exposure, contrasting with declines in chlorophyll content and productivity under pre-eclipse high irradiance. This study provides valuable insights into the rapid acclimation mechanisms of Lessonia spicata to transient light stress, highlighting its sensitivity and resilience to sudden shifts in solar irradiance. These findings contribute to the broader field of marine macroalgal photobiology and stress physiology, enhancing our understanding of how intertidal brown algae adapt to dynamic environmental conditions. Full article

Background: Natural astaxanthin, a commercially valuable carotenoid, is primarily sourced from Haematococcus pluvialis, a microalga known for its remarkable resilience to environmental stress. Methods: In this study, the physiological and transcriptomic responses of H. pluvialis to ND were investigated at various time points under high light conditions. Results: Under high light conditions, nitrogen deprivation (ND) enhances astaxanthin content (33.23 mg g⁻¹) while inhibiting the formation of the secondary cell wall (SCW), increasing astaxanthin content by 29% compared to the nitrogen-replete group (25.64 mg g⁻¹); however, the underlying mechanisms remain unclear. ND reduced chlorophyll fluorescence parameters, elevated reactive oxygen species (ROS) levels, and increased starch and total sugar accumulation while decreasing protein and lipid content. Fatty acid content increased on the first day but had declined by the fifth day. A transcriptomic analysis revealed substantial alterations in gene expression in response to ND. Genes associated with the TCA cycle, glycolysis, astaxanthin biosynthesis, and cell motility were upregulated, while those involved in photosynthesis, lipid synthesis, ribosome biogenesis, amino acid synthesis, and SCW synthesis were downregulated. Additionally, ND modulated the expression of genes involved in ROS scavenging. Conclusions: These findings provide critical insights into the adaptive mechanisms of H. pluvialis in response to ND under high light, contributing to the development of strategies for enhanced production of astaxanthin-rich motile cells. Full article

Prolonged sleep deprivation impairs brain function and increases the risk of mental health disorders. Cichorium intybus L. Oligo-polysaccharides (JSO), bioactive compounds derived from chicory, belong to the category of food-medicine homologous substances, possess gut microbiota-modulating and anti-inflammatory properties, and serve as a natural prebiotic, having significant research value in food science. This research examined the anxiolytic properties of JSO in a murine model subjected to chronic sleep deprivation (CSD) stress and explored the mechanisms behind this effect, providing experimental evidence for the development of Cichorium intybus L. as a functional food. Specific pathogen-free (SPF) KM male mice were allocated at random into six experimental groups: the control group, the CSD model group, the diazepam (10 mg/kg) group, and the JSO treatment groups at low (50 mg/kg), medium (100 mg/kg), and high (200 mg/kg) doses. Following 3 weeks of CSD, anxiety-like behaviors were assessed using the open field test, elevated plus maze test, light–dark box test, forced swim test, and marble-burying test. To analyze the composition of gut microbiota, 16S rRNA sequencing was employed, while protein expression in the BDNF, PI3K/AKT/mTOR, and NLRP3 inflammasome pathways was detected by Western blot. Behavioral analysis indicated that JSO (at doses of 100 and 200 mg/kg) markedly enhanced both the time allocated to open arms and the number of entries into open arms in the elevated plus maze test (p < 0.05). JSO (at doses of 50 and 200 mg/kg) significantly elevated transitions in the light–dark box test (p < 0.05), all JSO doses drastically cut down marble-burying behavior (p < 0.001, p < 0.01, p < 0.01). The 16S rRNA sequencing indicated that JSO intervention increased Bacteroidetes abundance while reducing Actinobacteria. Western blot analysis demonstrated that JSO significantly downregulated the ratios of p-mTOR/mTOR, p-PI3K/PI3K, p-AKT/AKT, BAX/BCL-2, as well as the expression levels of NLRP3, ASC, Caspase-1, and IL-6 proteins (p < 0.05), while upregulating hippocampal BDNF (p < 0.05). These results indicate that JSO ameliorates CSD-induced anxiety-like behaviors by restoring gut microbiota homeostasis, regulating the BDNF-PI3K/AKT/mTOR and BAX/BCL-2 apoptosis pathways, and suppressing NLRP3 inflammasome-mediated neuroinflammation. Full article

Background: Exposure to household air pollution (HAP) is one of the primary risk factors for acute lower respiratory infection (ARI) morbidity and mortality among children in low-income settings. This study aimed to examine the relative contribution of residing in deprived neighbourhoods and exposure to HAP on the occurrence of ARI among children using data from the 2014–2015 Chad Demographic and Health Survey (DHS). Methods: We applied multilevel modelling techniques to survey data of 2882 children from 372 communities to compute the odds ratio (OR) for the occurrence of ARI between children of respondents exposed to clean fuels (e.g., electricity, liquid petroleum gas, natural gas, and biogas) and respondents exposed to polluting fuel (e.g., kerosene, coal/lignite, charcoal, wood, straw/shrubs/grass, and animal dung). Results: The results showed that children exposed to household polluting fuels in Chad were 215% more likely to develop ARI than those not exposed to household air pollution (OR = 3.15; 95% CI 2.41 to 4.13). Further analysis revealed that the odds of ARI were 185% higher (OR = 2.85; 95% CI 1.73 to 4.75) among children living in rural residents and those born to teenage mothers (OR = 2.75; 95% CI 1.48 to 5.15) who were exposed to household polluting fuels compared to their counterparts who were not exposed. In summary, the results of the study show that the risk of ARI is more common among children who live in homes where household air-polluting cooking fuel is widely used, those living in rural areas, those living in socioeconomically deprived neighbourhoods and from the least wealthy households, and those born to teenage mothers in Chad. Conclusions: In this study, an independent relative contribution of variables, such as HAP from cooking fuel, neighbourhood deprivation, living in rural areas, being from a low-income household, having a mother who is a manual labourer worker, and being given birth to by a teenage mother, to the risk of ARI among children is established. Full article

Objectives: Ischemic stroke is a severe neurological disorder with high morbidity, mortality, and disability rates, posing a substantial burden on patients, families, and healthcare systems. Soy isoflavone (SI), a naturally occurring phytoestrogen, has demonstrated promising neuroprotective effects. This study aimed to evaluate the anti-stroke efficacy of SI and elucidate its underlying mechanisms through integrated phytochemical profiling, network pharmacology, and both in vitro and in vivo experimental validation. Methods: Active constituents of SI were extracted via reflux and identified using liquid chromatography–mass spectrometry (LC-MS). Network pharmacology was employed to predict therapeutic targets and signaling pathways. The neuroprotective effects of SI were first assessed in PC12 cells subjected to oxygen–glucose deprivation/reoxygenation (OGD/R) injury in vitro. For in vivo evaluation, transient cerebral ischemia–reperfusion injury was induced using the bilateral common carotid artery occlusion (BCCAO) model in adult male ICR rats (27.3 ± 1.8 g; 6–8 weeks old), obtained from the Shanghai Experimental Animal Center, Chinese Academy of Sciences. Forty-eight rats were randomly assigned into four groups (n = 12): sham, model (BCCAO), SI-treated (100 mg/kg, oral gavage for 5 days), and edaravone (EDA)-treated (10 mg/kg, i.p., positive control). All procedures were approved by the Institutional Animal Care and Use Committee of Changchun Normal University (Approval No. 2024003, 13 March 2024) and conducted in accordance with the NIH guidelines and ARRIVE 2.0 reporting standards. Results: In vitro, SI significantly enhanced PC12 cell viability from 57.23 ± 2.88% to 80.76 ± 4.43% following OGD/R. It also reduced intracellular Ca²⁺ by 58.42%, lactate dehydrogenase (LDH) release by 37.67%, caspase-3 activity by 55.05%, and reactive oxygen species (ROS) levels by 74.13% (p < 0.05). A flow cytometry analysis revealed that OGD/R increased the apoptosis rate from 5.34% (control) to 30.85% (model group), which was significantly attenuated by SI treatment, especially in the 560 µg/mL group (20.00%), followed by the 140 and 280 µg/mL groups. In vivo, SI improved neurological scores from 8.3 ± 1.09 to 6.8 ± 1.68, reduced cerebral infarction volume by 18.49%, and alleviated brain edema by 10.42% (p < 0.05). SI also decreased malondialdehyde (MDA) and LDH levels by 31.15% and 39.46%, respectively, while increasing the activity of antioxidant enzymes: superoxide dismutase (SOD) by 11.70%, catalase (CAT) by 26.09%, and glutathione peroxidase (GSH-px) by 27.55% (p < 0.01). Scratch assay results showed that SI restored the impaired migratory ability of the OGD/R-treated PC12 cells, further supporting its role in cellular repair. A Western blot analysis demonstrated the upregulation of nuclear factor erythroid 2–related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and NAD(P)H:quinone oxidoreductase 1 (NQO1) and the downregulation of Kelch-like, ECH-associated protein 1 (Keap1) in the cerebral ischemia–reperfusion model. Conclusions: These findings indicate that soy isoflavone confers significant neuroprotective effects against cerebral ischemia–reperfusion injury by enhancing endogenous antioxidant defense mechanisms, reducing oxidative stress, inhibiting apoptosis, and promoting cell migration. The protective effects are likely mediated through the activation of the Nrf2/Keap1 signaling pathway, supporting the therapeutic potential of SI in ischemic stroke treatment. Full article

It has always been understood that Pablo Picasso imbued his arts with a rich symbolism. Those representations could be understood readily, at times only with some effort, or utterly inaccessible at others. A part of that symbolism is yet to be understood, with numerous points of information and cross-reference “hiding” in plain sight. He was fond of newsprint as a substrate and medium for painting, not only during wartime, but especially so in the deprivations of World War II. The relationship between some paintings typical during the period and the newsprint on which they were done was intense, such that the substrate inhabits the medium, sharing equal part with the composition. Around the same time or after, Picasso was crafting poems of an often cryptic nature. An in-depth look at two poems reveals a multitude of references to paintings on newsprint and to the contents of that newsprint. With new understandings of those symbols, evidence emerges that Picasso’s “palette of words” was more than just metaphor, but also descriptive of a theory and a method which the artist put into practice in at least two instances of WWII-era newsprint paintings and famously cryptic poems, detailed here. Full article

Sustainably farmed Atlantic salmon could drive global food system solutions by contributing essential nutrients to the human diet while delivering high-quality protein. One of the biggest obstacles to sustainable salmon aquaculture in Chile is the prevalence of piscirickettsiosis disease caused by the Gram-negative bacteria Piscirickettsia salmonis and the excessive amount of antibiotics used to eradicate this disease. Farmed salmon products can be consumed without prior processing and therefore present a substantial risk for the transfer of resistant pathogens to humans. Antibiotics also carry the risk of antibiotic residues and damage to the environment. An alternative to antibiotics is the use of natural antimicrobials without the negative influence on the consumer’s microbiome. Here, we evaluate the potential antimicrobial activity against P. salmonis of the marine microalgae Microchloropsis gaditana. A non-genetically modified M. gaditana was grown with nitrogen deprivation to improve the synthesis of the eicosapentaenoic fatty acid (EPA). A spray-dried M. gaditana concentrate (Mg) was elaborated and given to Atlantic salmon for a period of 49 days, and serum and fillet samples were collected. Our results showed a significant increase in the nutritional quality improving the levels of EPA+ Docosapentaenoic acid (DPA) (23%) and Vitamin D₃ (106%) of the fillets treated with Mg. Fish fed serum were challenged with P. salmonis, and serum antibacterial activity was measured. Sera from fish fed Mg-enriched diets showed a significant increase in antibacterial activity (85.68%) against P. salmonis. Our results indicate that Mg can be used as a viable alternative to address the critical problem of microbial resistance and to assure consumers that farm-raised Atlantic salmon is safe. Full article

Background/Objectives: Sleep-disordered breathing (SDB) is a primary concern in children’s health. Research suggests that repeated oxygen drops during sleep—common in SDB—may harm the brainstem’s breathing control centres. This damage likely occurs through oxidative stress, inflammation, and cell death, which weaken the brain’s ability to regulate breathing. Over time, these effects could lead to functional changes (e.g., disrupted chemical signalling) and physical damage in critical brain regions, creating a cycle of unstable breathing. However, much of this evidence comes from animal or lab studies, leaving gaps in our understanding of how these mechanisms work in humans. This review synthesises existing research on how breathing disruptions during sleep—particularly episodes of intermittent hypoxia—affect the brain’s ability to control respiration in children and adolescents. Methods: We analysed studies from medical databases PubMed, Scopus, and Web of Science, focusing on how SDB (obstructive or central sleep apnoea) impacts the brain’s respiratory centres in young populations. Animal studies and research involving children on mechanical ventilation were excluded to focus on natural sleep patterns. Results: After removing duplicates, 54 studies remained. Additionally, 43 record were excluded for various reasons. Ultimately, 11 articles were selected for the final analysis, including three that focused on genetic conditions, such as Down syndrome, Prader–Willi syndrome, and Pierre Robin sequence. The findings suggest that repeated oxygen dips during sleep may harm the brainstem’s respiratory control areas, especially during critical developmental stages. This damage could lead to long-term issues, such as unstable breathing, cardiovascular strain, or neurological problems. However, most studies only captured the immediate effects of low oxygen, leaving uncertainty about permanent harm due to a lack of long-term follow-up. Conclusions: Repeated oxygen deprivation during sleep appears to damage the brainstem and disrupt breathing regulation. However, small study sizes and short observation periods limit the strength of these conclusions. Future research should use advanced imaging tools to clarify long-term risks, develop effective treatments, and track children over extended periods. More significantly, longer-term studies are urgently needed to guide clinical care for vulnerable populations. Full article

Aggressive behavior not only negatively affects an individual’s psycho-social adaptation but also undermines social harmony and stability. This study investigated the relationship between perceived crowdedness and aggression, examining the mediating role of relative deprivation and the moderating effects of upward social comparison and connectedness to nature based on the general strain theory and the I³ model. A cross-sectional design was employed, involving 848 participants (524 females, 61.8%) aged 20–75 (M = 33.15, SD = 6.83) in China. Structural equation modeling and bootstrapping procedures were used to test the hypothesized moderated mediation model. The results indicated that perceived crowdedness and upward social comparison positively predicted aggressive behavior, whereas connectedness to nature negatively predicted it. Relative deprivation mediated the relationship between perceived crowdedness and aggressive behavior. Only upward social comparison moderated the relationship between perceived crowdedness and relative deprivation, and connectedness to nature showed a marginally significant moderating effect on the relationship between perceived crowdedness and aggressive behavior. Unexpected trends are discussed, along with directions for future research. Full article

A detailed characterization of the mechanism of action of garlic extract (GE) on prostate cancer (PCa) cells is essential to ensure its safe use as a complementary therapy, particularly when combined with established treatments. A case report highlighted the potential benefits of GE in PCa management. A patient diagnosed with PCa, presenting an initial prostate-specific antigen (PSA) of 11.8 ng/mL, maintained PSA levels between 3.5 and 6 ng/mL for over 14 years with daily GE intake. To study GE’s anti-proliferative effects and interactions with established therapeutics, healthy prostate epithelial cells (PNT2) and PCa cells (LNCaP, PC3, VCaP) were treated with GE. Proliferation, Integrin β1 pattern, DNA-damage, as well as androgen receptor (AR) and Cytochrome P450 (CYP450) expression were investigated. GE reduced the proliferation of LNCaP and PC3 cells compared to healthy PNT2 cells but had contrary effects on VCaP cells. The combination of GE with standard therapies, including chemotherapy, androgen deprivation therapy (ADT), and Poly-(ADP-ribose)-Polymerase inhibitors (PARPi), reduced the efficacy of these treatments in tumor cells, potentially due to the GE-induced upregulation of the metabolic enzyme CYP2C9 in PCa cell lines. These findings indicate that while GE has anti-proliferative effects, the use of highly concentrated natural extracts must be carefully assessed by expert physicians on a case-by-case basis, especially when combined with established therapies. Full article

Background: Despite scientific breakthroughs in vaccine development, some people remain reluctant to accept the anti-SARS-CoV-2 vaccine. This study evaluates attitudes and behaviours towards the vaccine and factors associated with refusal/hesitancy at the start of Italy’s vaccination campaign. Methods: EPICOVID19 is a two-phase observational web-based study where adult volunteers completed questionnaires in April–June 2020 and January–February 2021. Refusal/hesitancy towards the vaccine was assessed among those not yet vaccinated. We analysed factors associated with refusal/hesitancy by applying multivariate multinomial logistic regression models. Results: Among 36,820 survey participants (mean age of 51 years, 59.7% women, 63.6% highly educated), 2449 (6.7%) were against or hesitant, 4468 (12.1%) were inclined but unsure, and 29,903 (81.2%) were willing to be vaccinated. Factors positively associated with refusal/hesitancy included female sex, middle age, at-risk occupations, medium and low education, deprived status, being underweight, previous SARS-CoV-2 positivity, poor perceived health, no fear of contracting SARS-CoV-2, the fear of contaminated food and natural disasters, and low trust in science, media, government, or institutions. Low hesitancy was associated with student and retired status, overweight and obesity, moderate and high alcohol consumption, no concern about economic and working conditions, and sensitivity to climate change/environmental pollution and epidemics. Conclusions: This survey showed that, during the first month of Italy’s vaccination campaign, some individuals were reluctant to receive the anti-SARS-CoV-2 vaccine. This study highlights potential target groups for tailored communication and prevention campaigns. Full article

The COVID-19 pandemic has exacerbated the challenges faced by children in Malaysia, particularly in terms of poverty and hardship. This has led to concerns about the long-term impact on children’s welfare, particularly in terms of educational and economic inequalities. The multidimensional nature of poverty is often overlooked in public policy discussions, and most countries use National Multidimensional Poverty Indices (MPIs) to define child poverty levels within a nation. This article aims to compare the results of a child-specific Multidimensional Poverty Index (MPI) with those of a household-specific MPI, considering the uncertainty surrounding the capacity of Household MPIs to accurately identify multidimensionally impoverished children. This study, conducted in Pahang, Malaysia, uses survey data to examine the multidimensional child poverty status and its dynamic changes. The modified child poverty headcount ratio, using the Alkire–Foster methodology, evaluates both the traditional headcount ratio of child poverty and the mean level of deprivation among disadvantaged children. The results indicate low poverty rates in Pahang and its districts. Increased policy attention has been called for due to rising unemployment among parents and the increasing number of bereaved children due to the pandemic. Full article