Search Results (5,672)

Cardiac transplantation remains an important therapy for end-stage heart failure, although allograft rejection continues to pose significant clinical challenges. This review evaluates both established and emerging blood-based biomarkers for noninvasive monitoring of rejection in heart transplant recipients. Donor-derived cell-free DNA (ddcfDNA) and gene expression profiling (GEP) represent well-validated, commercially available molecular tools that demonstrate strong discriminative capacity for acute rejection episodes. Additionally, microRNAs (miRs) and extracellular vesicles (EVs) show considerable potential as novel biomarkers, although further validation is required. In contrast, conventional biomarkers such as B-type natriuretic peptide (BNP), cardiac troponins, and creatine kinase-MB (CK-MB) offer limited specificity in the context of rejection. This review synthesizes current evidence on the clinical utility, methodological challenges, and integration strategies of these biomarkers, highlighting a shift toward molecular-based approaches for improving post-transplant surveillance and patient outcomes. Full article

The design features and applications of button sample holders are described. The similarities and contrasts between the button method and the transmission cell and attenuated total reflection techniques are discussed. Different button sample holder analysis methodologies are outlined, and examples are provided for mid-infrared spectroscopy measurements of solids, liquids, and pastes. Results obtained for 10-nonadecanone powder, a vitamin C tablet, a soil sample, and poly(methyl methacrylate) are used to illustrate different solid sample analysis approaches. Time-dependent spectrum variations detected during evaporation of a blood drop are elucidated and spectra obtained from different quantities of liquid chlorobenzene loaded into buttons and transmission cells are characterized. Infrared spectra derived from three toothpaste brands are compared and a sample perturbation study to identify temperature-dependent changes to the structure of poly(bisphenol A carbonate) is provided as an example of variable temperature infrared spectroscopy. Full article

Background/Objectives: Red blood cell (RBC) transfusion is frequently used to treat anemia of prematurity, yet bedside metrics that capture its short-term impact on oxygenation stability are limited. We assessed whether pulse oximetry histogram-derived oxygen saturation (SpO₂) exposure changes after transfusion and whether responses differ across clinical subgroups. Methods: This prospective observational cohort included preterm infants born <32 weeks’ gestation who received a standardized RBC transfusion (15 mL/kg). Continuous SpO₂ histograms quantified the percentage of monitored time spent in hypoxemia (<85%), normoxemia (86–95%), and hyperoxemia (≥96%) during four intervals: 24 h pre-transfusion and 24, 48, and 72 h post-transfusion. Repeated-measures and subgroup analyses (BPD, sex, birth weight < 1000 g) were performed. Results: Thirty-three infants were analyzed (gestational age 29.4 ± 2.1 weeks; birth weight 1220.6 ± 316.9 g). Hemoglobin increased from 8.6 ± 1.1 to 11.7 ± 1.0 g/dL (p < 0.001). Cohort-level histogram shifts were modest: normoxemia increased from 68.4 ± 12.1% to 72.6 ± 11.4% at 24 h (p = 0.18), hypoxemia decreased from 10.3 ± 6.5% to 6.6 ± 4.8% (p = 0.09), and hyperoxemia remained stable (21.3 ± 9.2% to 20.8 ± 8.5%; p = 0.44). Infants with BPD and those <1000 g showed persistently higher hypoxemia and/or hyperoxemia at 72 h compared with counterparts. Exploratory ROC analyses showed modest discrimination of 24 h hypoxemia for ROP (AUC 0.71) and 72 h hyperoxemia for BPD (AUC 0.74). Conclusions: RBC transfusion corrected anemia but did not produce a consistent cohort-level improvement in SpO₂ histogram stability. Histogram metrics may help characterize heterogeneous oxygenation responses and support hypothesis generation for individualized monitoring strategies. Full article

Peripheral inflammation is increasingly recognized as a critical driver of sustained neuroinflammation and cognitive dysfunction in neurodegenerative and inflammation-associated disorders. Systemic inflammatory mediators can compromise blood–brain barrier integrity, activate glial cells, and initiate maladaptive neuroimmune cascades that disrupt hippocampal–prefrontal circuits underlying learning and memory. Here, we investigated whether early systemic administration of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) mitigates inflammation-driven cognitive deficits in a chronic lipopolysaccharide (LPS) mouse model. Adult mice received daily LPS injections for seven days to induce persistent systemic and central inflammation, which was confirmed by serum and hippocampal cytokine analyses in a separate cohort at the time of MSC administration, followed by intravenous MSC treatment immediately after cessation of the inflammatory insult. Behavioral testing revealed significant impairments in spatial working memory, recognition memory, and associative learning. These deficits were accompanied by pronounced microglial activation, immune cell accumulation, astrocytosis, and a shift toward a pro-inflammatory cytokine milieu with suppression of IL-10 in the hippocampal CA1 region and medial prefrontal cortex. Early MSC treatment attenuated glial reactivity, reduced pro-inflammatory cytokines, restored IL-10 expression, and partially rescued cognitive performance. Collectively, these findings identify a post-inflammatory therapeutic window in which early MSC-based immunomodulation can rebalance neuroimmune signaling and limit inflammation-induced hippocampal–prefrontal circuit dysfunction, highlighting a clinically relevant strategy for targeting cognitive impairment associated with chronic systemic inflammation. Full article

Time-resolved spectroscopy (TRS) is a promising tool for noninvasive cerebral monitoring in neonates. However, the optimal forehead site for probe placement remains unclear. In this study, we evaluated the effect of probe positioning on TRS-derived optical parameters in neonates. TRS measurements were obtained from the midline and right lateral forehead of 30 neonates (≥36 weeks’ corrected gestational age). We compared various parameters between the two probe positions, including optical intensity, attenuation, mean optical path length, scattering coefficient, total hemoglobin (tHb), cerebral oxygen saturation (ScO₂) and cerebral blood volume (CBV). No significant differences were observed in tHb, ScO₂ and CBV between the midline and lateral sites. However, the lateral site showed a significantly lower scattering coefficient and shorter mean path length. Light intensity was increased and attenuation was reduced at the lateral site. Thus, while tHb, ScO₂ and CBV values were consistent between sites, the midline provided more stable scattering and optical path data. These findings suggest that the midline forehead may be a more suitable site for TRS-based neonatal cerebral monitoring. Full article

Acute respiratory distress syndrome (ARDS) is a major cause of morbidity and mortality despite decades of progress in ventilatory support. Mechanical ventilation, while essential for oxygenation, may exacerbate lung injury through excessive mechanical power delivery, even when using lung-protective strategies. Extracorporeal carbon dioxide removal (ECCO₂R) was conceived to enable “ultra-protective” ventilation, allowing for further reductions in tidal volume and respiratory rate by selectively removing CO₂ at low extracorporeal blood flows, typically between 0.3 and 1.0 L/min. This physiological decoupling of ventilation and gas exchange aims to mitigate ventilator-induced lung injury (VILI) while maintaining adequate acid–base homeostasis. Although early physiological studies demonstrated feasibility, large, randomized trials have failed to show a survival benefit and have raised concerns about bleeding and technical complications. Recent evidence suggests that these neutral outcomes may stem from the biological and physiological heterogeneity of ARDS rather than from inefficacy of the intervention itself. Patients with high driving pressures, poor compliance, or hyperinflammatory phenotypes may derive greater benefit from ECCO₂R-mediated mechanical unloading. Ongoing technological improvements, including circuit miniaturization, enhanced biocompatibility, and integration with renal replacement therapy, have improved safety and feasibility, yet the procedure remains complex and resource-intensive. Future research should focus on phenotype-enriched trials and the integration of ECCO₂R into precision ventilation frameworks. Ultimately, ECCO₂R should be regarded not as a universal therapy for ARDS but as a targeted physiological tool for selected patients in experienced centers. Full article

Background: Inflammatory activity in rheumatoid arthritis can be determined by normal blood count ratios such as Neutrophil Lymphocyte Ratio (NLR), Platelet Lymphocyte Ratio (PLR), Systemic Immune Inflammation Index (SII), and C-reactive Protein (CRP). Objective: The aim of this research is to determine how these markers change after therapy and whether their pre- and post-treatment differences follow patterns that allow for simple parametric analyses. Methods: A prospective cohort of 52 RA patients (30 females and 22 males) was examined. The patients’ blood samples were tested at baseline and at the end of their 6-month Infliximab treatment. Hematologic markers such as NLR, PLR, and SII were calculated from the complete blood count (CBC), and CRP levels were measured. The statistical methods of Shapiro–Wilk (SW), Kolmogorov–Smirnov (KS), and Anderson–Darling (AD) were used, and later, paired t-tests were used to generate statistics where necessary. Results: Post-treatment measurements were consistently lower for all four biomarkers. QQ-plots and formal tests revealed that the differences between findings were essentially normal, allowing for paired t-tests. The mean decreases were as follows: NLR −1.10 (95% CI −1.48 to −0.71), PLR −43.0 (−55.4 to −30.7), SII −299 (−388 to −211), and CRP −11.36 (−13.18 to −9.54), all p < 0.001. CRP showed the greatest drop, with significant decreases in PLR and SII and a moderate decline in NLR, indicating therapy-related attenuation of systemic inflammation. Conclusions: The study shows that six months of infliximab therapy results in a consistent post-treatment decrease in all four biomarkers: NLR, PLR, SII, and CRP. Because the pre-post differences were roughly normal, CRP revealed the greatest decrease, with significant decreases in PLR and SII and a moderate decrease in NLR, consistent with systemic inflammation reduction. When combined, the CBC-derived indices track with CRP and can serve as practical, low-cost markers for monitoring therapy response in RA, despite the single-arm design. Full article

The World Health Organization estimates that about 15% of couples in their adult years in industrialized countries experience infertility, which is described as the inability of a sexually active and non-contraceptive couple to achieve spontaneous pregnancy within a year. Environmental pollution is a significant health concern worldwide and one of the possible risk factors leading to male infertility. Cadmium is a common heavy toxin derived from industrial activities, a ubiquitous environmental pollutant, and can cause severe harm to various organs including the testis. Cadmium toxicity can lead to severe impairment of male germ cells in both rodents and humans, which can result in azoospermia. The negative effects of cadmium on the testicles are caused by its induction of oxidative stress, spermatogenic apoptosis, and testicular inflammation or its detriment to androgenic and sperm cell functions, which damages the vascular endothelium and blood–testis barrier. Overall, this review describes the detrimental impact of cadmium on the testicles and its effect on male infertility. Therefore, by considering recent research findings and identifying future research directions, this review underlines the need to develop new treatments for male infertility related to heavy metal exposure. Full article

Retinal astrocytes reside mainly in the nerve fiber layer and are central to shaping retinal vessels and maintaining neurovascular balance. Derived from the optic nerve head, they spread across the inner retina to form a meshwork that both supports and instructs the emerging superficial vascular plexus. Immature astrocytes supply vascular endothelial growth factor-A(VEGF-A) to guide endothelial sprouting, while signals from growing vessels promote astrocyte maturation and strengthen the blood–retinal barrier. In disorders such as diabetic retinopathy and neovascular age-related macular degeneration, these cells show marked plasticity. Reactive astrogliosis can sustain VEGF and inflammation, favoring fragile, leaky neovessels, whereas alternative astrocyte states help reinforce barrier function and release anti-angiogenic factors. Located at the core of the neurovascular unit, astrocytes communicate continuously with endothelial cells, pericytes and neurons. This review integrates data from single-cell profiling and advanced imaging to outline astrocyte development, morphology and key signaling pathways (VEGF, PDGF, Wnt/Norrin, Eph/ephrin), and considers how tuning astrocyte polarization might be exploited to preserve retinal vascular integrity. Full article

Defective HIV-1 proviruses harboring mutations and/or large internal deletions represent the majority of HIV-1 sequences found in circulating peripheral blood mononuclear cells of people living with HIV with viremia suppressed by combination antiretroviral therapy; indirect evidence suggests that such sequences are transcriptionally active and may contribute to immune activation. In this study, we present a new approach allowing for high-efficiency screening, immortalization, and targeted enrichment of HIV-positive CD4⁺ T-cells isolated from people living with HIV. Using this method, we were able to isolate and expand patient-derived cells, identify mutations and deletions via sequencing, and confirm that those proviruses were transcriptionally and translationally active in vitro. Moreover, our findings indicate that the majority of proviral sequences circulating in suppressed HIV-infected patients may undergo 3′-LTR deletions, suggesting that sequence diversity reported using LTR-to-LTR amplification and sequencing approaches may indeed be underscored. Full article

Background/Objectives: Branched-chain fatty acids (BCFAs) exhibit a range of biological activities; however, their limited natural abundance and high cost have constrained in vivo research. Lanolin represents a promising source for enriching BCFAs. Nevertheless, the in vivo application, safety, and dose-effect relationship of BCFAs derived from lanolin (BCFAs-DFL) remain unassessed. Methods: In this study, the acute toxicity in C57BL/6J mice was first evaluated for 7 days by a single oral administration of 5000 mg/kg BW of BCFAs-DFL. Subsequently, 40 mice were divided into four groups (control group, low dose of 100 mg/kg BW, medium dose of 300 mg/kg BW, and high dose of 600 mg/kg BW) and were continuously administered by gavage for 28 days to study the effects of BCFAs-DFL on the growth, blood biochemistry, intestinal morphology, and intestinal flora of the mice. Results: In the acute toxicity test, BCFAs-DFL exhibited no lethality or abnormalities in mice, indicating its non-toxic nature. Throughout the 28-day trial, mice in the medium- and high-dose groups experienced a notable decrease in average daily feed intake (p < 0.05), yet their weight gain remained unaffected (p > 0.05). Hemoglobin and hematocrit levels declined in the high-dose group (p < 0.05). Conversely, serum aspartate aminotransferase and total bilirubin levels escalated in the medium- and high-dose groups, while triglycerides and urea nitrogen levels decreased (p < 0.05). The serum’s total antioxidant capacity and immunoglobulin levels (IgA, IgG) rose in proportion to the dosage (p < 0.05). BCFAs-DFL notably enhanced the villus height of the jejunum and ileum in mice (p < 0.05). Gut microbiota analysis indicated no significant impact on overall α and β diversity. Conclusions: The 28-day intervention revealed that BCFAs-DFL can modulate feeding behavior, TG, T-AOC, and immunoglobulin levels in mice. Additionally, it promotes the development of intestinal villi. Based on various indicators, a dosage of 100 mg/kg BW effectively induces beneficial metabolic regulation, such as the reduction of triglycerides, without causing a burden on liver metabolism. This dosage may represent a more suitable application for potential use. Full article

Background/Objectives: Neovascularization, defined as the sprouting of new blood vessels from pre-existing vasculature, is a critical pathological feature in ocular diseases such as pathological myopia and represents a leading cause of corneal vision loss. Vascular endothelial growth factor A (VEGFA) plays a pivotal role in endothelial cell proliferation, migration, survival by anti-apoptotic signaling, and vascular permeability. Dysregulation of VEGFA is closely linked to pathological neovascularization. Exosomes, nanosized phospholipid bilayer vesicles ranging from 30 to 150 nm, have emerged as promising gene delivery vehicles due to their intrinsic low immunogenicity, superior cellular uptake, and enhanced in vivo stability. This study aimed to investigate whether highly purified mesenchymal stem cell (MSC)-derived exosomes loaded with VEGFA siRNA labeled with FAM can effectively suppress pathological corneal neovascularization (CNV) via targeeted cellular transduction and VEGFA inhibition. Furthermore, we examined whether the therapeutic effect involves the modulation of the PI3K–Akt–Caspase-3 signaling axis. Methods: Exosomes purified by chromatography were characterized by electronmicroscopy, standard marker immunoblotting, and nanoparticle tracking analysis. In vitro, we assessed exosome uptake and cytoplasmic release, suppression of VEGFA mRNA/protein, cell viability, and apoptosis. In a mouse CNV model, we evaluated tissue reach and stromal retention after repeated intrastromal injections; anterior segment angiogenic indices; CD31/VEGFA immunofluorescence/immunoblotting; phosphorylated PI3K and Akt; cleaved caspase-3; histology (H&E); and systemic safety (liver, kidney, and spleen). Results: Exosomes were of high quality and showed peak efficacy at 48 h, with decreased VEGFA mRNA/protein, reduced viability, and increased apoptosis in vitro. In vivo, efficient delivery and stromal retention were observed, with accelerated inhibition of neovascularization after Day 14 and maximal effect on Days 17–19. Treatment reduced CD31 and VEGFA, decreased p-PI3K and p-Akt, and increased cleaved caspase-3. Histologically, concurrent reductions in neovascularization, inflammatory cell infiltration, and inflammatory epithelial thickening were observed, alongside a favorable systemic safety profile. Conclusions:VEGFA siRNA-loaded exosomes effectively reduce pathological CNV via a causal sequence of intracellular uptake, cytoplasmic release, targeted inhibition, and phenotypic suppression. Supported by consistent PI3K–Akt inhibition and caspase-3–mediated apoptosis induction, these exosomes represent a promising local gene therapy that can complement existing antibody-based treatments. Full article

Background/Objectives: Insulin resistance and ambulatory blood pressure monitoring (ABPM) abnormalities represent distinct but interrelated pathways contributing to cardiovascular risk. The triglyceride–glucose (TyG) index reflects metabolic burden, whereas arterial load—captured through arterial stiffness, blood pressure variability, and morning surge—reflects hemodynamic instability. Whether the coexistence of these domains identifies a particularly high-risk ambulatory phenotype remains unclear. To evaluate the independent and combined effects of metabolic burden (TyG) and arterial load on circadian blood pressure pattern and short-term systolic blood pressure variability. Methods: This retrospective cross-sectional study included 294 adults who underwent 24 h ABPM. Arterial load was defined using three ABPM-derived indices (high AASI, high SBP-ARV, high morning surge). High metabolic burden was defined as TyG in the upper quartile. The “double-high” phenotype was classified as high TyG plus high arterial load. Primary and secondary outcomes were non-dipping pattern and high SBP variability. Multivariable logistic regression and Firth penalized models were used to assess independent associations. Predictive performance was evaluated using ROC analysis. Results: The double-high phenotype (n = 15) demonstrated significantly higher nighttime SBP, reduced nocturnal dipping, and markedly elevated BP variability. It was the strongest independent predictor of non-dipping (adjusted OR = 42.0; Firth OR = 11.73; both p < 0.001) and high SBP variability (adjusted OR = 41.7; Firth OR = 26.29; both p < 0.001). Arterial load substantially improved model discrimination (AUC = 0.819 for non-dipping; 0.979 for SBP variability), whereas adding TyG to arterial load produced minimal incremental benefit. Conclusions: The coexistence of elevated TyG and increased arterial load defines a distinct hemodynamic endotype characterized by severe circadian blood pressure disruption and exaggerated short-term variability. While arterial load emerged as the principal determinant of adverse ambulatory blood pressure phenotypes, TyG alone demonstrated limited discriminative capacity. These findings suggest that TyG primarily acts as a metabolic modifier, amplifying adverse ambulatory blood pressure phenotypes predominantly in the presence of underlying arterial instability rather than serving as an independent discriminator. Integrating metabolic and hemodynamic domains may therefore improve risk stratification and help identify a small but clinically meaningful subgroup of patients with extreme ambulatory blood pressure dysregulation. Full article

Despite major advances in guideline-directed cardiovascular therapy, residual cardiovascular risk persists, partly driven by oxidative stress, chronic inflammation, endothelial dysfunction, and mitochondrial injury not fully addressed by current drugs. Translation of plant-based cardioprotectants is constrained by preparation-dependent variability in extract chemistry (plant part/cultivar/processing and extraction method), low and variable systemic exposure for key actives (notably curcuminoids and many polyphenols), and clinically relevant safety/interaction considerations (e.g., hepatotoxicity reports with concentrated green tea extracts and antiplatelet-related bleeding-risk considerations for some botanicals). We therefore provide a mechanism- and translation-oriented synthesis of evidence for cardioprotective botanicals, chosen for long-standing traditional use and scientific validation with reproducible experimental data and, where available, human studies, including Crataegus monogyna, Allium sativum, Olea europaea, Ginkgo biloba, Leonurus cardiaca, and Melissa officinalis. Across studies, polyphenols (especially flavonoids and phenolic acids) and organosulfur compounds are most consistently associated with cardioprotection, while terpene-derived constituents and secoiridoids contribute mechanistically in plant-specific settings (e.g., Ginkgo and Olea). Predominantly in experimental models, these agents engage redox-adaptive (Nrf2), mitochondrial (mPTP), endothelial, and inflammatory (NF-κB) pathways, with reported reductions in ischemia–reperfusion injury, oxidative damage, and apoptosis. Clinical evidence remains heterogeneous and is largely confined to short-term studies and surrogate outcomes (blood pressure, lipids, oxidative biomarkers, endothelial function), with scarce data on hard cardiovascular endpoints or event reduction. Priorities include standardized, chemotype-controlled formulations with PK/PD-guided dosing and adequately powered randomized trials that assess safety and herb–drug interactions. 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