Search Results (1,411)

The development of severe SARS-CoV-2 pneumonia is characterized by extensive lung inflammation, which, in turn, leads to respiratory distress and a decline in blood oxygen levels. Hospital admission, along with intensive care or ventilator usage, becomes necessary because this condition leads to serious respiratory problems. This review aims to provide a comprehensive overview of the pathophysiological mechanisms, diagnostic methods, and current therapeutic options for pneumonia caused by the SARS-CoV-2 virus. The pathophysiological process of severe pneumonia due to SARS-CoV-2 infection is characterized by direct lung damage from viral replication, an excessive immune system response, inflammation, impaired gas exchange, and multi-organ failure. The coexistence of various medical conditions leads to substantial lung impairment, resulting in hypoxia and respiratory failure, which can ultimately lead to fatal outcomes. The diagnosis of severe SARS-CoV-2 pneumonia is made through a combination of clinical, radiologic, and laboratory findings. A multifaceted approach integrating antiviral therapy, corticosteroids, oxygen supplementation, ventilatory management, and immunomodulation is imperative to control inflammation and enhance clinical outcomes. Early intervention, meticulous monitoring, and personalized care are paramount for enhancing survival and mitigating complications in critically ill patients with COVID-19 pneumonia. Full article

Atopic dermatitis (AD) is a common chronic inflammatory skin disorder characterized by immune dysregulation and skin barrier impairment. This study evaluated the anti-inflammatory and immunomodulatory effects of Camellia japonica extract in a 2,4-dinitrochlorobenzene (DNCB)-induced AD mouse model using SKH-1 hairless mice. Topical application of Camellia japonica extract for four weeks significantly alleviated AD-like symptoms by reducing epidermal thickness, mast cell infiltration, and overall skin inflammation. Hematological analysis revealed a marked decrease in total white blood cell (WBC) and neutrophil counts. Furthermore, the Camellia japonica extract significantly decreased oxidative stress, as evidenced by reduced serum reactive oxygen species (ROS) and nitric oxide (NO) levels, while enhancing the activity of antioxidant enzymes such as catalase. Importantly, allergic response markers including serum immunoglobulin E (IgE), histamine, and thymic stromal lymphopoietin (TSLP), were also downregulated. At the molecular level, Camellia japonica extract suppressed the expression of key pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β, and T helper 2 (Th2)-type cytokines such as IL-4 and IL-5, while slightly upregulating the anti-inflammatory cytokine IL-10. Collectively, these findings suggest that Camellia japonica extract effectively modulates immune responses, suppresses allergic responses, attenuates oxidative stress, and promotes skin barrier recovery. Therefore, application of Camellia japonica extract holds the promising effect as a natural therapeutic agent for the prevention and treatment of AD-like skin conditions. Full article

We examined the physiological demands of trained rowers across four exercise intensity domains (considering the effects of weight category and sex). Twenty-four trained rowers (12 lightweight and 12 heavyweight) performed 7 × 3 min incremental bouts on a Concept2 rowing ergometer (30 W power increases and 60 s rest intervals). Performance, cardiorespiratory and metabolic responses were continuously assessed throughout the experimental protocol to characterize internal load across progressive exercise intensities. Statistical analyses included a repeated measures ANOVA test and independent t-tests (p ≤ 0.05). Heavyweight rowers exhibited greater absolute anaerobic energy production in the severe domain (41.25 ± 10.39 vs. 32.54 ± 5.92 kJ) (p = 0.02), higher peak metabolic power (up to 1.57 ± 0.30 vs. 1.48 ± 0.30 kW) (p = 0.001) and greater total energy expenditure (up to 277.52 ± 51.23 vs. 266.69 ± 51.59 kJ) (p = 0.001) than lightweight rowers, whereas the latter showed comparable relative cardiorespiratory responses to heavyweights. With respect to sex differences, males demonstrated higher oxygen uptake (from ~43–59 vs. ~34–48 mL·kg⁻¹·min⁻¹) (p = 0.001), ventilation (from ~78–146 vs. ~49–99 L·min⁻¹) (p = 0.001), metabolic power (from ~1.1–1.7 vs. ~0.7–1.0 kW) (p = 0.001) and energy expenditure (from ~193–305 vs. ~119–209 kJ) (p = 0.001) across all intensity domains. However, blood lactate levels and anaerobic energy contributions were similar between sexes. These findings demonstrated that domain-based physiological profiling effectively differentiates internal responses among rowers by weight category and sex. Heavyweights showed greater absolute energy output, while lightweights demonstrated higher metabolic efficiency. Males had elevated cardiorespiratory and metabolic values, but relative bioenergetic responses were similar across groups. These findings support individualized training based on physiological profiles. Full article

Background/Objectives: Gut-derived tryptophan (Trp) metabolites play important roles in metabolic and cardiovascular regulation. Although animal studies suggest their protective effects against metabolic dysfunction, data in adolescents, particularly those with obesity, remain limited. The objective of this study was to evaluate associations between circulating gut-derived Trp metabolites and markers of cardiometabolic, vascular, and platelet health in adolescents with obesity. Methods: Data were analyzed from 28 adolescents (ages 13–18; mean BMI = 36 ± 6.4 kg/m²). Fasting blood was collected to assess lipid profiles using a clinical analyzer and insulin resistance using the homeostatic model assessment for insulin resistance (HOMA-IR). Gut-derived Trp metabolites were measured by UPLC–mass spectrometry, peak oxygen uptake (VO_{2 peak}) by gas exchange during an incremental cycle ergometer test, and body composition by dual-energy X-ray absorptiometry. Platelet spare respiratory capacity (SRC), endothelial function, and liver fat were measured using high-resolution respirometry, flow-mediated dilation (FMD) of the brachial artery, and magnetic resonance imaging respectively. Results: Indole-3-propionic acid was inversely associated with diastolic blood pressure (rho = −0.39, p = 0.047), total cholesterol (rho = −0.55, p = 0.002), and LDL-C (rho = −0.57, p = 0.0014), independent of sex and obesity severity. Indoxyl sulfate was positively correlated with fasting glucose (rho = 0.47, p = 0.012), and adolescents with impaired fasting glucose had 1.6-fold higher IS levels. Indole-3-acetaldehyde declined with age (rho = −0.50, p = 0.007), and Indole-3-acetic acid and indole were higher in Hispanics vs. non-Hispanics. No significant associations were observed between Trp metabolites and FMD, VO₂ peak, or SRC. Conclusions: Gut-derived Trp metabolites, particularly indole-3-propionic and indoxyl sulfate, are associated with markers of cardiometabolic risk in adolescents with obesity. These findings support their potential relevance in early-onset cardiovascular disease risk. Full article

In familial Alzheimer’s disease (FAD), presenilin 1 (PSEN1) E280A cholinergic-like neurons (ChLNs) induce aberrant secretion of extracellular amyloid beta (eAβ). How PSEN1 E280A ChLNs-eAβ affects microglial activity is still unknown. We obtained induced microglia-like cells (iMG) from human peripheral blood cells (hPBCs) in a 15-day differentiation process to investigate the effect of bolus addition of Aβ42, PSEN1 E280A cholinergic-like neuron (ChLN)-derived culture supernatants, and PSEN1 E280A ChLNs on wild type (WT) iMG, PSEN1 E280A iMG, and sporadic Alzheimer’s disease (SAD) iMG. We found that WT iMG cells, when challenged with non-cellular (e.g., lipopolysaccharide, LPS) or cellular (e.g., Aβ42, PSEN1 E280A ChLN-derived culture supernatants) microenvironments, closely resemble primary human microglia in terms of morphology (resembling an “amoeboid-like phenotype”), expression of surface markers (Ionized calcium-binding adapter molecule 1, IBA-1; transmembrane protein 119, TMEM119), phagocytic ability (high pHrodo™ Red E. coli BioParticles™ phagocytic activity), immune metabolism (i.e., high generation of reactive oxygen species, ROS), increase in mitochondrial membrane potential (ΔΨm), response to ATP-induced transient intracellular Ca²⁺ influx, cell polarization (cluster of differentiation 68 (CD68)/CD206 ratio: M1 phenotype), cell migration activity according to the scratch wound assay, and especially in their inflammatory response (secretion of cytokine interleukin-6, IL-6; Tumor necrosis factor alpha, TNF-α). We also found that PSEN1 E280A and SAD iMG are physiologically unresponsive to ATP-induced Ca²⁺ influx, have reduced phagocytic activity, and diminished expression of Triggering Receptor Expressed on Myeloid Cells 2 (TREM2) protein, but when co-cultured with PSEN1 E280A ChLNs, iMG shows an increase in pro-inflammatory phenotype (M1) and secretes high levels of cytokines IL-6 and TNF-α. As a result, PSEN1 E280A and SAD iMG induce apoptosis in PSEN1 E280A ChLNs as evidenced by abnormal phosphorylation of protein TAU at residue T205 and cleaved caspase 3 (CC3). Taken together, these results suggest that PSEN1 E280A ChLNs initiate a vicious cycle between damaged neurons and M1 phenotype microglia, resulting in excessive ChLN death. Our findings provide a suitable platform for the exploration of novel therapeutic approaches for the fight against FAD. Full article

Reward processing is a vital function for health and survival and is impaired in various psychiatric and neurological disorders. Using a monetary gambling task, the current study aims to elucidate neural substrates in the reward network underlying the evaluation of win versus loss outcomes and their association with behavioral characteristics, such as impulsivity and task performance, and neuropsychological functioning. Functional MRI was recorded in thirty healthy, male community volunteers (mean age = 27.4 years) while they performed a monetary gambling task in which they bet with either 10 or 50 tokens and received feedback on whether they won or lost the bet amount. Results showed that a set of key brain structures in the reward network, including the putamen, caudate nucleus, superior and inferior parietal lobule, angular gyrus, and Rolandic operculum, had greater blood oxygenation level-dependent (BOLD) signals during win relative to loss trials, and the BOLD signals in most of these regions were highly correlated with one another. Furthermore, exploratory bivariate analyses between these reward-related regions and behavioral and neuropsychological domains showed significant correlations with moderate effect sizes, including (i) negative correlations between non-planning impulsivity and activations in the putamen and caudate regions, (ii) positive correlations between risky bets and right putamen activation, (iii) negative correlations between safer bets and right putamen activation, (iv) a negative correlation between short-term memory capacity and right putamen activity, and (v) a negative correlation between poor planning skills and left inferior occipital cortex activation. These findings contribute to our understanding of the neural underpinnings of monetary reward processing and their relationships to aspects of behavior and cognitive function. Future studies may confirm these findings with larger samples of healthy controls and extend these findings by investigating various clinical groups with impaired reward processing. Full article

Nicotine-induced oxidative stress contributes significantly to vascular endothelial dysfunction. While negative air ions (NAIs) demonstrate potential blood-pressure-regulating and antioxidant properties, their mechanistic role remains unclear. This study examined the effects of NAIs against nicotine-induced oxidative damage and vascular endothelial injury in spontaneously hypertensive rats (SHRs). Western blotting was used to detect the expression levels of the α7nAChR/MAPK/AP1 pathway. Transcriptomic sequencing was performed to identify the differentially expressed genes after treatment with nicotine or NAIs. Furthermore, reactive oxygen species (ROS), endothelin-1 (ET-1), and [Ca²⁺]_i levels were detected in human aortic endothelial cells (HAECs) treated with nicotine, and the relationship between transcription factor activator protein 1 (AP1) and the target genes was further elucidated through ChIP–qPCR. Nicotine exposure in SHRs elevated blood pressure and induced oxidative damage through α7nAChR/MAPK/AP1 pathway activation, causing endothelial structural disruption. These effects manifested as decreased NO/eNOS and increased ET-1/ET_ab expression, while these changes were reversed by NAIs. In HAECs, nicotine impaired proliferation while increasing oxidative stress and [Ca²⁺]_i levels. This endothelial damage was markedly attenuated by either NAIs or fibronectin 1 (Fn1)/secreted phosphoprotein 1 (Spp1) knockdown. Mechanistically, we identified AP1 as the transcriptional regulator of FN1 and SPP1. NAIs attenuate nicotine-induced endothelial dysfunction in hypertension by inhibiting AP1-mediated FN1 and SPP1 activation, providing novel insights for smoking-associated cardiovascular risk. Full article

Medicinal plants have been traditionally used for generations, often without scientific validation. Euphorbia tirucalli (E. tirucalli), a plant native to Africa, is commonly employed in folk medicine for treating various ailments, including cancer. However, most studies involving this species are limited to in vitro models, and its systemic effects remain poorly understood. This study aimed to evaluate the impact of E. tirucalli latex on renal function in healthy Wistar rats. Animals were divided into two groups: a control group receiving water and a treated group receiving E. tirucalli latex (13.47 mg/kg) by gavage for 15 days. Renal function was assessed by measuring glomerular filtration rate (GFR), renal plasma flow (RPF), renal blood flow (RBF), renal vascular resistance (RVR), and mean arterial pressure (MAP). Additionally, oxidative stress markers, reactive oxygen/nitrogen species, and inflammatory activity were analyzed in renal tissue. E. tirucalli significantly reduced GFR, RPF, and RBF, while increasing RVR and MAP. Renal tissue exhibited elevated levels of advanced oxidation protein products, myeloperoxidase, nitric oxide, and peroxynitrite/hydroxyl radicals. These findings indicate that E. tirucalli latex adversely affects renal hemodynamics and promotes oxidative and inflammatory damage, suggesting potential nephrotoxic effects, even in healthy subjects. Full article

A properly functioning capillary microcirculation is essential for sufficient oxygen and nutrient delivery to the central nervous system. The physical mechanisms governing the transport of red blood cells (RBCs) inside the narrow and irregularly shaped capillary lumen are complex, but understanding them is essential for identifying the root causes of neurological disorders like cerebral ischemia, Alzheimer’s disease, and other neurodegenerative conditions such as concussion and cognitive dysfunction in systemic inflammatory conditions. In this work, we conducted numerical simulations of three-dimensional capillary models, which were acquired ex vivo from a mouse retina, to characterize RBC transport. We show how the spatiotemporal velocity of the RBCs deviates in realistic capillaries and equivalent cylindrical tubes, as well as how this profile is affected by hematocrit and red cell distribution width (RDW). Our results show a previously unprecedented level of RBC velocity fluctuations in capillaries that depends on the geometric features of different confinement regions and a capillary circularity index $\left(I_{cc}\right)$ that represents luminal irregularity. This velocity fluctuation is aggravated by high hematocrit conditions, without any further effect on RDW. These results can provide a better understanding of the underlying mechanisms of pathologically high capillary transit time heterogeneity that results in microcirculatory dysfunction. Full article

Background. The venom of Loxoscelesrufescens (L.r.), also known as the violin and/or brown spider, contains a wide variety of proteins and can induce a complex, intense, and uncontrolled inflammatory response, hemolysis, thrombocytopenia, dermo-necrosis, and renal failure. Studies have postulated the efficacy of hyperbaric oxygen therapy (HBOT) for Loxosceles bites. However, data describing the use and beneficial effects of HBO are, to date, relatively scarce. Only a few cases of Loxosceles bites in Northern Italy have been documented, and there is no laboratory test available for the diagnosis. Objectives. We present seven cases (aged 54.5 ± 4.2 years) of patients who presented to the emergency room (E.R.) of Niguarda Hospital in Milan from March to October 2022. Methods. Blood and urine samples were collected and biomarkers of oxidative stress (OxS) (reactive oxygen species (ROS), total antioxidant capacity (TAC), lipid peroxidation (8iso-PFG2α), DNA damage (8-OH-dG)), inflammation (IL-6, IL-1β, TNF-α, sICAM1), and renal function (creatinine, neopterin, uric acid) before (T0), during (T1, T2), and after (1–2 wk T3–T4; 1 month T5) the HBOT treatment (US Navy Treatment Table 15 protocol) were studied. Results. At T0, patients showed a significant unbalance of OxS; high levels of ROS, 8-isoPGF2α, and inflammatory status (IL-6, TNF-α; sICAM); and a low level of antioxidant capacity. At the end of HBOT (T2), a significant reduction in Oxy-inflammation levels over time—8-iso −26%, 8-OH-dG −9%, IL-6 −71%, IL-1bβ −12%, TNF-α −13%, and sICAM1 −17%—associated with clinical improvement was shown. Conclusions. These reductions, along with those in renal function markers, mirrored the observed improvement in the evolution of the skin lesion and the patients’ self-reported general wellness and pain. In conclusion, HBOT should be considered a valuable therapeutic tool after L.r. bites. Full article

Background: Modulating ethanol metabolism and attenuating alcohol-induced oxidative stress are promising therapeutic strategies for reducing the severity of hangovers and alleviating their associated physiological burden. Methods: A randomized, double-blind, placebo-controlled, crossover study was conducted to evaluate the effects of the probiotic strain Leuconostoc mesenteroides VITA-PB2 on ethanol metabolism, oxidative stress, and hangover-related symptoms in 28 healthy adults. The participants consumed either VITA-PB2 or a placebo before standardized alcohol intake, with a 7-day washout period and subsequent crossover. Primary outcomes included blood ethanol, acetaldehyde levels, and aldehyde dehydrogenase (ALDH) activity. Secondary outcomes measured hangover severity assessed by the Acute Hangover Scale (AHS), liver enzymes including aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma-glutamyl transferase (GGT), oxidative stress indicators reactive oxygen species (ROS) and nitric oxide (NO), and antioxidant responses measured by glutathione peroxidase (GPx), catalase, and 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging capacity. Results: VITA-PB2 supplementation led to a sustained reduction in blood ethanol concentrations beginning at 0.5 h post-ingestion compared with the placebo group, indicating more efficient ethanol clearance. Additionally, VITA-PB2 significantly reduced acetaldehyde levels at 1 h post-ingestion (p < 0.05) and increased ALDH activity by 42.15% at 30 min (p < 0.05). It also markedly reduced ROS levels at 1 h (p < 0.05), enhanced glutathione peroxidase (GPx) activity at 2 h (p < 0.01), and significantly improved the subjective hangover symptoms, particularly thirst (p < 0.05). Conclusions: No adverse effects were reported during the trial, indicating that Leuconostoc mesenteroides VITA-PB2 is a safe probiotic. These findings suggest its efficacy in mitigating alcohol-induced oxidative stress and alleviating hangover-related symptoms. Full article

Interstitial pneumonia is a general term for diseases in which inflammation occurs mainly in the interstitium of the lung. It is also pointed out that interstitial pneumonia reduces alveolar function and makes it difficult to take in oxygen through inspiration, causing symptoms such as dyspnea and coughing, which may eventually lead to respiratory failure. At present, there is no effective treatment, and only conservative treatment exists. This time, we report that the therapeutic effect was confirmed in patients with interstitial pneumonia who took platinum palladium. In this case, improvement tendencies were observed in patients with Idiopathic pulmonary fibrosis (IPF), but improvement tendencies were also observed in many other lung diseases. In order to explore the mechanism, AMPK was measured at the in vitro level, and blood KL-6 and hydrogen peroxide levels in the patient were measured at the in vivo level. AMPK values were significantly elevated by more than 800%, and KL-6 and hydrogen peroxide levels were also significantly decreased by drinking platinum palladium. Platinum palladium exhibits a strong antioxidant effect and is the only substance in the world that can approach all four types of active oxygen. In addition, when it was actually administered to patients, there were cases of dramatic improvement, and it was confirmed that KL-6, a parameter of lung function, decreased in 16 out of 32 patients, and furthermore, oxygen inhalation was completed. Patients were also seen. It was suggested that increasing the number of cases in the future may help improve interstitial pneumonia. Full article

In coastal waters, tributyltin chloride (TBTC), a persistent organic pollutant, is extensively present. It is uncertain, therefore, if exposure to TBTC can harm haarders and how. This study exposed the fish for 60 days in order to investigate the molecular mechanism of haarder following TBTC poisoning. Our findings demonstrated that growth indices dropped, liver tissue was damaged, and the liver’s total tin concentration rose following TBTC exposure. Furthermore, we discovered that blood reactive oxygen species rose while total blood cell count decreased. As malondialdehyde levels rose, total antioxidant capacity and antioxidant enzyme activity (superoxide dismutase, catalase, and glutathione peroxidase) were markedly reduced. After being exposed to TBTC, liver cells displayed clear signs of apoptosis. Differentially expressed genes were primarily linked to oxidative stress, energy metabolism, and apoptosis, according to the transcriptome study of livers. Overall, the long-term stress of TBTC resulted in the antioxidant system being harmed, as well as serious malfunction of the energy metabolism and apoptotic response. Full article

In acute myeloid leukemia (AML) it is important to elucidate the biological events that lead from remission to relapse, which have a high probability of leading to an adverse disease outcome. The cancer stem cell marker aldehyde dehydrogenase 1 (ALDH1A1) is underexpressed in AML cells when compared to healthy cells, both at the RNA level and at the protein level, and at least in the former, both in the bone marrow and in peripheral blood. Nonetheless, ALDH1A1/ALDH1A2 activity increases in AML cells during disease relapse and is higher in adverse prognosis AML in comparison with favorable prognosis AML. Furthermore, especially in relapsed AML and in unfavorable AML, AML cells rich in ALDH1A1 can contain high levels of reactive oxygen species (ROS), in parallel with high ALDH1A1/2 activity. This metabolic feature is clearly incompatible with normal stem cells. The term “stem-like” therefore is useful to coin malignant cells with a variety of genetic makeups, metabolic programming and biomarkers that converge in the function of survival of clones sufficient to sustain, spread and re-establish neoplastic disease. Therefore, AML “stem-like” cells survive cancer treatment that eradicates other malignant cell clones. This fact differentiates AML “stem-like” cells from normal stem and progenitor cells that function in tissue regeneration as part of a distinct hierarchical order of cell phenotypes. The ODYSSEY clinical trial is a Phase I/II study designed to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of ABD-3001, a novel therapeutic agent, in patients with AML who have relapsed or are refractory to standard treatments. In this context, ABD-3001 is used as an inhibitor of cytosolic ALDH1 enzymes, such as ALDH1A1 and ALDH1A2. Full article

Fungi are ubiquitous organisms that are capable of transient or persistent colonization in humans. Their polymorphic nature and complex host–mycobiome interactions remain incompletely understood. Emerging evidence highlights the role of resident fungi in modulating immune responses and adapting to host changes, which can trigger a shift from commensalism to parasitism, particularly in immunocompromised individuals. This study evaluated the effects of two major β-glucans—zymosan and curdlan—on the expression of pattern recognition receptors (Dectin1, Dectin2, TLR2, TLR4) in human peripheral blood mononuclear cells (PBMCs). It also examined their impact on reactive oxygen species (ROS) production, cytokine/chemokine gene expression, and antioxidant enzyme expression. Both β-glucans significantly increased the mRNA levels of all tested receptors and enhanced ROS generation. Curdlan downregulated key antioxidant enzymes (SOD1, CAT, GPX1), while zymosan markedly upregulated SOD1. These findings demonstrate that the β-glucans zymosan and curdlan have a substantial influence on PBMC reactivity and oxidative stress responses. Further studies are needed to deepen our understanding of host–fungal interactions and their implications in health and disease. Full article