Search Results (472)

Noninvasive light-based measurements have recently been suggested for monitoring fracture healing and for the development of smart implants. The aim of this study was to collect the first exploratory longitudinal in vivo data from human distal fibular fractures. In this prospective observational pilot study, blood flow, oxygen saturation, and relative hemoglobin were noninvasively measured by using combined laser Doppler and white-light spectroscopy at depths of 3 mm and 10 mm. In patients with fibular fractures, measurements were performed at 1–3 days, 2 weeks, 6 weeks, 3 months and 6 months after surgery. Patients with fibular nonunion and healthy control participants underwent a single measurement. Fourteen longitudinal fracture patients, a nonunion patient, and 42 controls were included. In the longitudinal fracture group, oxygen saturation at a depth of 10 mm significantly decreased from baseline to 2 weeks (p < 0.001) and remained at a low plateau significantly below healthy control levels throughout the 6-month period. Blood flow and relative hemoglobin levels did not longitudinally change but remained significantly elevated compared with controls (p < 0.001). A single nonunion case demonstrated a markedly low oxygen saturation value (8.3%) combined with increased blood flow. Fibular fractures treated with plate fixation exhibit a prolonged low-oxygen saturation plateau, in contrast to the rapid recovery observed in tibial shaft fractures, possibly due to differences in anatomy or healing mechanisms. The low oxygen saturation observed in the nonunion requires further investigation, as it may have prognostic potential. Full article

Long non-coding RNAs (lncRNAs) have emerged as important regulators of developmental processes. Recent studies have established roles for lncRNAs in human and murine erythroid regulation, yet additional regulators remain to be discovered. To identify lncRNA candidates involved in human erythroid regulation, we established a pooled genome-editing screen strategy using human embryonic stem cells (hESCs). Long Intergenic Non-Protein Coding RNA 1089 (LINC01089) was selected for functional investigation. We found that reduced LINC01089 expression impaired erythroid differentiation. Transcriptomic profiling revealed consistent downregulation of genes related to hemoglobin assembly, heme biosynthesis, and membrane maturation, suggesting that LINC01089 supports coordinated erythroid transcriptional programs. In particular, progressive reduction of HBB expression emerged as a key transcriptional anchor. Enrichment analyses of upregulated genes identified recurrent focal adhesion signatures, suggesting a potential link between LINC01089 and focal adhesion kinase (FAK)-related signaling. Given prior evidence linking LINC01089 to FAK phosphorylation, we performed a pilot FAK-inhibition experiment, producing a partial shift toward wild-type HBB expression and supporting FAK/phosphorylated FAK (pFAK) signaling as a potential contributing axis in the impaired transcriptional programs. Together, our findings identify LINC01089 as a novel lncRNA linked to coordinated heme–globin transcriptional programs in human erythroid differentiation, with possible involvement of the FAK/pFAK axis. Full article

Cancer is a leading cause of death in humans and dogs. Several erythrocyte and platelet characteristics (indices and morphology) have shown promise as indicators of metastasis in humans. Similar studies have not been performed in dogs. This study evaluated erythrocyte and platelet characteristics measured on the Advia 2120i in 59 tumor-bearing dogs with carcinoma or sarcoma. Tumor-bearing dogs with and without intracavitary hemorrhage that underwent complete post-mortem and histopathology examinations were compared to healthy age-controlled dogs. Carcinoma- and sarcoma-bearing dogs without hemorrhage were compared. All tumor-bearing dogs without hemorrhage or metastasis were compared to those with metastasis, and characteristics were evaluated as indicators of metastasis. Tumor-bearing dogs without intracavitary hemorrhage (n = 49) had decreased hematocrit (p = 0.002) and reticulocyte hemoglobin content (p = 0.022), and increase in anisocytosis (p = 0.002), polychromasia (p = 0.002), macrocytosis (p = 0.032), codocytes (p = 0.022), absolute reticulocyte count (p = 0.035), platelet concentration (p = 0.002), plateletcrit (p = 0.022), and platelet volume distribution width (p = 0.022) compared to healthy dogs (n = 20). In tumor-bearing dogs with intracavitary hemorrhage (n = 10), additional significant differences were reflective of acute hemorrhage. No difference in characteristics between carcinoma- and sarcoma-bearing dogs without hemorrhage was identified. After correction for multiple comparisons, no differences in erythrocyte or platelet characteristics were identified between tumor-bearing dogs without intracavitary hemorrhage and metastasis and those without metastasis. Significant differences in characteristics exist between tumor-bearing dogs and healthy dogs. Based on the limited number of dogs in this preliminary study, no red blood cell or platelet characteristics were associated with metastatic disease in tumor-bearing dogs without hemorrhage. Full article

Alcohol-related liver disease (ALD) and ALD-related mortality are associated with hemolysis, increased erythrophagocytosis, and disturbed iron homeostasis. While macrophage-mediated erythrophagocytosis is well established, we investigated the contribution of liver sinusoidal endothelial cells (LSECs) to handling oxidatively damaged or ethanol-primed red blood cells (RBCs) in ALD. Live-cell imaging demonstrated that damaged RBCs were rapidly taken up by SK-HEP1 cells, an endothelial cell line with LSEC-like characteristics, and RBC uptake was associated with induction of heme oxygenase-1 (HO-1) and activation of its upstream regulator Nrf2. siRNA-mediated knockdown of the scavenger receptor Stabilin-1 attenuated RBC-induced HO-1 expression, supporting a role for Stabilin-1 in efferocytic signaling. Exposure of RBCs to ethanol concentrations as low as 25 mM induced phosphatidylserine externalization and rendered erythrocytes efferocytosis-competent. Lysed RBCs and free hemin elicited comparable oxidative stress responses. In murine models of hemolysis and chronic ethanol feeding, hemoglobin-derived signals were detected within sinusoidal structures showing a diffuse CD206-positive distribution pattern consistent with the sinusoidal scavenger compartment. Similar signals were observed in sinusoidal endothelial regions in human heavy drinkers with clinical signs of hemolysis. Together, these data suggest that LSECs may represent an additional component of RBC clearance in ALD, alongside macrophages and hepatocytes, with implications for hepatic iron handling. Full article

Background/Objectives: Oral iron supplementation is widely used to treat iron deficiency but frequently causes gastro-intestinal side effects that limit treatment adherence. Unabsorbed luminal iron has been proposed to influence intestinal microbial communities, yet the effects of different oral iron doses on the human gut microbiome remain insufficiently characterized. Methods: In this randomized open-label study, 30 healthy premenopausal women with iron deficiency without anaemia received either low-dose oral iron supplementation (6 mg twice daily) administered under fasting conditions or standard-dose iron supplementation (100 mg once daily) taken with a meal for four weeks. Stool samples were collected before and after treatment and analyzed using 16S rRNA sequencing to evaluate microbiome composition. Results: Baseline characteristics, including age, body mass index, hemoglobin concentration and serum ferritin, were comparable between groups. After four weeks of treatment, distinct alterations in gut microbiome composition were observed between the low-dose and standard-dose groups. The genera Colidextribacter and GCA-900066575 decreased in the low-dose group but increased in the standard-dose group, whereas Oscillospira showed the opposite pattern. Gastrointestinal adverse events were reported by 87% of participants receiving standard-dose iron supplementation compared with 7% receiving low-dose iron supplementation (p < 0.0001). Conclusions: Oral iron supplementation induces dose-dependent changes in the intestinal microbiome and higher doses are associated with substantially increased gastrointestinal intolerance. These findings suggest that lower iron doses may reduce microbiome disruption and improve treatment tolerability. Full article

Background and Objectives: Intraoperative assessment of tissue perfusion remains a decisive but imperfect step in abdominal surgery. Surgeons still rely heavily on visual judgement when choosing bowel transection lines, constructing anastomoses, judging intestinal viability, or assessing graft reperfusion, even though these decisions are directly linked to anastomotic leak, conduit ischemia, postoperative liver dysfunction, and graft failure. Hyperspectral imaging (HSI) is an emerging contrast-free optical technology that generates quantitative maps of tissue oxygenation, hemoglobin distribution, water content, and near-infrared perfusion. The present review was designed to evaluate whether clinical intraoperative HSI has matured sufficiently to support a focused systematic review topic in abdominal surgery and to synthesize the currently available human evidence. Methods: A literature search was conducted up to 20 February 2026 using combinations of the terms “hyperspectral imaging”, “HSI”, “abdominal surgery”, “colorectal”, “hepatectomy”, “transplantation”, “pancreatoduodenectomy”, “esophagectomy”, “mesenteric ischemia”, and “intraoperative”. Eligible records were original human clinical studies evaluating intraoperative HSI in abdominal or transplant-related operations with perfusion, oxygenation, or tissue viability as a central endpoint. Review articles, animal studies, non-surgical diagnostic studies, and single-patient case reports were excluded. Data were synthesized narratively because of major heterogeneity in indications, designs, devices, timing of measurements, and reported outcomes. Results: Thirteen studies published between 2019 and 2024 met the eligibility criteria, representing 391 patients. The literature covered colorectal resection, acute mesenteric ischemia, esophageal reconstruction with gastric or colonic conduits, pancreatoduodenectomy, pancreas transplantation, major hepatectomy, liver transplantation, and minimally invasive system validation. Across colorectal studies, HSI frequently demonstrated discordance between visually selected and objectively perfused transection lines, with clinically relevant strategy changes in a substantial proportion of patients. In ischemic and transplant settings, HSI discriminated poorly perfused tissue, identified low near-infrared perfusion values associated with early allograft dysfunction, and quantified reperfusion patterns after clamping or implantation. The evidence base was dominated by prospective single-center feasibility studies with small to moderate sample sizes, and no randomized trials were identified. Conclusions: Clinical intraoperative HSI in abdominal surgery is a genuinely niche yet rapidly expanding topic with a sufficient number of human studies to support a relevant systematic review. Current evidence consistently supports feasibility, quantitative perfusion discrimination, and plausible intraoperative utility, especially in colorectal and transplant-related surgery. However, the field remains methodologically heterogeneous, and the next research priority is multicenter standardization with clinically anchored thresholds and outcome-driven comparative studies. Full article

Delayed cerebral ischemia (DCI) is a major complication of aneurysmal subarachnoid hemorrhage (aSAH), strongly associated with neurological deterioration and poor outcomes. Its pathophysiology remains incompletely understood and involves multiple interacting processes. Increasing evidence highlights the role of redox imbalance triggered by hemoglobin breakdown and the subsequent generation of reactive species, leading to vascular dysfunction, impaired nitric oxide signaling, and inflammatory activation This review aims to summarize current knowledge on redox-related mechanisms involved in DCI and to explore the potential role of the peroxiredoxin (PRDX) family in this setting. A narrative review of experimental and preclinical studies was performed, focusing on molecular pathways associated with vascular regulation, cellular injury, and antioxidant defense. Particular attention was given to the distribution and biological functions of PRDX isoforms within the central nervous system. This work addresses a topic not previously systematically discussed, the potential involvement of PRDX proteins in aSAH-related complications. By integrating available data, it provides a conceptual framework linking PRDX to mechanisms relevant for DCI. The manuscript serves as a starting point for future research, particularly translational and clinical studies in humans, which are necessary to verify the relevance of these findings and to better understand their potential clinical implications. Full article

Objectives: To investigate the effects of Roxadustat and recombinant human erythropoietin (rHuEPO) on glycemic control and glycated hemoglobin (HbA1c) in non-dialysis type 2 diabetic kidney disease (DKD) patients with anemia. Methods: This retrospective study enrolled 449 patients, who were divided into three groups—the rHuEPO group (n = 252), the Roxadustat group (n = 102), and the switch group (n = 95)—in which patients were converted from rHuEPO to Roxadustat. All treatments lasted for more than three months. Changes in HbA1c and other indicators within groups as well as differences among groups were evaluated. Results: In the rHuEPO group, HbA1c levels decreased from 7.08 ± 1.19 to 6.41 ± 0.60 (p < 0.001), and they returned to baseline levels by 6–12 months (p > 0.05). In the Roxadustat group, HbA1c fluctuated but none of the differences reached statistical significance (p > 0.05). In the switch group, HbA1c decreased during rHuEPO treatment (p < 0.05) and returned to baseline after switching to Roxadustat (p > 0.05). No significant changes in blood glucose levels were observed in any group after treatment (p > 0.05). Multivariate linear regression analysis showed that changes in iron metabolism parameters, erythrocyte parameters, inflammatory markers, and glucose-lowering or lipid-lowering regimens had no significant effect on the change in HbA1c in the Roxadustat group (F = 0.834, p = 0.620), while the multivariate model of rHuEPO group also lacked statistical significance (F = 1.142, p = 0.170). After treatment, all three groups showed improvements in anemia, iron metabolism, renal function, inflammatory markers, and lipid profiles compared with baseline (p < 0.05). Additionally, further improvements in these parameters were observed after the transition from rHuEPO to Roxadustat (p < 0.05). Compared with rHuEPO group, the Roxadustat group exhibited significantly greater increases in hemoglobin, red blood cell count, total iron-binding capacity, transferrin, and serum iron (p < 0.05). Conclusions: In non-dialysis DKD patients with anemia, rHuEPO can significantly decrease HbA1c values, while Roxadustat does not. Roxadustat offers advantages over rHuEPO in terms of efficacy and assessment of glycemic control. Full article

Conventional cardiopulmonary resuscitation (CPR) is guided primarily by process metrics that do not directly quantify cerebral hemodynamics or perfusion. Near-infrared spectroscopy (NIRS) provides continuous, non-invasive monitoring of regional tissue oxygenation and has emerged as a candidate modality for physiologic feedback during low-flow states. However, CPR applications vary across devices and signal processing. This scoping review maps how NIRS has been implemented during conventional CPR in humans and porcine models, with emphasis on instrumentation characteristics, signal processing, acquisition bandwidth, artifact handling, physiologic associations, and feasibility constraints. From 1048 records, 39 studies met the inclusion criteria. Most used forehead-based cerebral rSO₂ monitoring (30/39). Rising cerebral oxygenation trajectories were consistently associated with return of spontaneous circulation (ROSC). In contrast, persistently low or non-increasing patterns were associated with non-ROSC, and absolute thresholds varied substantially across devices and studies. A minority of investigations derived compression-rate or waveform features from hemoglobin signals. Feasibility findings emphasized rapid probe placement without interrupting compressions but highlighted motion artifact, workflow constraints, and incomplete acquisition reporting. Overall, during conventional CPR, NIRS primarily serves as a dynamic monitor of oxygenation trends rather than a validated prognostic tool. Emerging waveform-based and hemodynamic analyses suggest the potential to evaluate CPR efficiency using perfusion-responsive optical features. Full article

Diabetes mellitus (DM) is a major disorder contributing to human mortality and morbidity globally. The use of medicinal plants in the management of diabetes is gaining global popularity due to their accessibility and cost-effectiveness. In this study, we evaluated the ameliorative potential of Vernonia amygdalina leaves crude extract (CE), free phenol (FP), and bound phenol (BP) fractions (50 mg/kg body weight) in a rat model of streptozotocin (STZ)-induced type 1 diabetes (T1DM). The effects of these treatments for 28 days on glucose, insulin, glycated hemoglobin, hepatic injury indices, and lipid profile were assessed in the serum. Furthermore, redox biomarkers (liver) and inflammatory mediators (serum and liver) were analyzed. Our results indicated that CE, FP, and BP fractions of Vernonia amygdalina inhibited the deleterious effects of T1DM by attenuating hyperglycaemia, insulin deficiency, hepatic injury, and dyslipidemia. Also, CE, FP, and BP fractions differentially improved antioxidant enzymes activity and reduced oxidative and inflammatory markers production. Specifically, CE showed superior effects compared with FP, BP, and metformin across multiple biomarkers, including glycated hemoglobin, α-amylase, α-glucosidase, hepatic glycogen, total cholesterol, LDL-cholesterol, protein carbonyl, SOD, IL-1β, and IL-10. The antidiabetic effects produced by CE, FP, and BP fractions of Vernonia amygdalina may be ascribed to the presence of different bioactive phytochemicals as revealed by HPLC analysis. Overall, our data would suggest a potential therapeutic role for Vernonia amygdalina leaves extracts in addressing hepatic complications due to T1DM. Full article

β-thalassaemia (β-thal) is part of a group of diseases, the β-hemoglobinopathies, affecting the levels or functionality of the β-globin subunit of hemoglobin, which are the most widespread monogenic diseases throughout the world. The severity of β-thal is determined by different genetic factors, but in the gravest form, affected patients are constrained to a program of blood transfusion and iron chelation regimens for their entire life. Although definitive cures, such as bone marrow transplantation or gene therapy, are now available, they are still far from being applied worldwide. Therefore, there is growing attention towards the use of drugs to cure or ameliorate β-thal disorder. Among all the strategies, pharmacological increase of fetal HbF and/or adult HbA2 can represent an advantageous approach as high levels of both hemoglobins are effective against β-thal. Therefore, the identification of therapeutic targets that can modulate, by the use of drugs, these hemoglobins is increasingly urgent. In this paper, we analyze the effects of the absence of the CCND3 gene, a druggable target associated with HbF and HbA2 levels, in a humanized mouse model of β-thal to assess the impact against the disorder. Upregulation of γ- and δ-globin levels in mice lacking Ccnd3 expression contributes to partial restoration of the α/β balance, with a consequent increase in hemoglobin levels, improvement of iron levels, and reduction of splenomegaly. Moreover, we present data supporting the enhancement of erythropoiesis. Our data indicate the CCND3 gene as a possible target for drugs against β-thal. Full article

Glutathionyl-hemoglobin (HbSSG) reversibly forms under oxidative stress in erythrocytes, where it constitutes the main redox buffer, in a dynamic equilibrium with the thiol (GSH) and disulfide (GSSG) forms of glutathione, that quickly revert to the reduced thiols when oxidative pressure is relieved. Under acute challenge, the “oxidized” GSH pool distributes between GSSG and HbSSG. Recalculation with electrochemical metrics based on redox potentials of the GSSG/GSH and HbSSG/HbSH pairs, plotted in their phase space, improves the understanding of the competing reduction processes. The first process is reduction of the GSSG pool, while, later, HbSSG reduction occurs as a two-step process. HbSSG accumulation in chronic oxidative stress follows an impairment of these steps. In 30 strong smokers, homogeneous levels of HbSSG are in the range of 2.4–11.7% (E_h −120–−95 mV), but the E_h of the GSSG/GSH redox pair is wider (−160–−240 mV), suggesting that HbSSG accumulation does not depend on GSH availability but on enzyme activity impaired by exogenous and endogenous electrophiles. As hinted by HbSSG measurements, one such species is the dehydro-alanine analog of GSH, produced both from butadiene in exposed petrochemical workers and from the drug busulfan in a treated patient. Inactivation of the low-copy recycling enzymes can thus explain the increase of HbSSG. Full article

Micronutrient deficiencies of iron and copper are global challenges that significantly undermine public health, particularly among vulnerable populations. Recent advancements in nanotechnology have paved the way for nano–micronutrient formulations that offer improved nutrient delivery over conventional supplements. Nano–micronutrients leverage sub-100 nm particle sizes, increased-surface area, and controlled-release mechanisms to enhance gastrointestinal absorption and bioavailability of iron and copper. This narrative review takes a nuanced approach to critically evaluate published literature comparing nano-formulations with traditional supplements, demonstrating that nano–micronutrients enable targeted cellular uptake, reduce interactions with anti-nutritional factors, and improve organoleptic properties of fortified foods. Evidence indicates that these formulations can markedly elevate clinical biomarkers such as serum ferritin and hemoglobin, while reducing required dosages and mitigating gastrointestinal side effects. However, challenges persist regarding long-term safety, production scalability, and regulatory oversight. Public acceptance remains contingent on transparent safety assessments and effective communication of benefits. Future research should focus on standardizing synthesis methods, developing green production processes, and integrating robust in vitro and in vivo models to elucidate long-term health impacts. Overall, nano–micronutrients of iron and copper hold transformative potential to alleviate micronutrient deficiencies and improve human nutrition, provided technical and regulatory challenges are adequately addressed. Full article

Diabetes mellitus remains a major global health burden, and many patients do not achieve durable glycemic control despite modern pharmacotherapy. This narrative review synthesizes evidence on plant-derived strategies that may complement standard care, focusing on two clinically aligned domains: glucose-lowering medicinal plants and plant-based sugar substitutes that reduce dietary glycemic load. We summarize key mechanistic pathways, including inhibition of α-amylase/α-glucosidase, reduced intestinal glucose entry and absorption kinetics, glucose-dependent insulinotropic effects, improved insulin signaling, suppression of hepatic gluconeogenesis, and microbiota-linked effects. We critically appraise human evidence for selected botanicals (cinnamon, fenugreek, mulberry, gymnema, gynura, rosehip, and Jerusalem artichoke) and plant sweeteners (stevia and monk fruit). Overall, clinical effects are modest and heterogeneous; the most reproducible signals are observed for mulberry leaf in blunting postprandial glucose excursions, and for cinnamon, fenugreek, and gymnema, where meta-analyses suggest modest improvements in glycemic markers. Stevia and monk fruit are best supported as glycemically neutral sucrose substitutes, while inulin-type fructans show small-to-moderate benefits with sustained intake, limited by gastrointestinal tolerability at higher doses. Key gaps include a shortage of long-term randomized trials using standardized preparations and durable endpoints such as glycated hemoglobin. Plant-derived interventions are therefore best positioned as adjuncts within individualized, evidence-based glycemic management. Full article

Visible-Near-Infrared (Vis-NIR) spectroscopy, spanning approximately 400 to 2500 nm, is an innovative technology with growing relevance for diagnostics performed at the point of care (POC). This review explores the potential of Vis-NIR in veterinary medicine, highlighting its advantages over complex techniques like Raman and Fourier transform infrared spectroscopy (FTIR) by being rapid, non-invasive, reagent-free, and compatible with miniaturized, portable devices. The methodology involves directing a broadband light source, often using LEDs, toward the sample (e.g., blood, urine, faeces), collecting spectral information related to molecular vibrations, which is then analyzed using chemometric methods. Successful veterinary applications include hemogram analysis in dogs, cats, and Atlantic salmon, and quantifying blood in ovine faeces for parasite detection. Key limitations include spectral interference from strong absorbers like water and hemoglobin, and the limited penetration depth of light. However, combining Vis-NIR with Self-Learning Artificial Intelligence (SLAI) is shown to isolate and mitigate these multi-scale interferences. Vis-NIR spectroscopy serves as an important complement to centralized laboratory testing, holding significant potential to accelerate clinical decisions, minimize stress on animals during assessment, and improve diagnostic capabilities for both human and animal health, aligning with the One Health concept. Full article