Blood Perfusion Research Articles

MT2A promotes angiogenesis in chronically ischemic brains through a copper–mitochondria regulatory mechanism

BackgroundApproximately half of patients with chronic ischemic cerebrovascular disease (CICD) exhibit poor revascularization. Metallothionein 2 A (MT2A) has a high affinity for metal ions and is potentially capable of chelating toxic copper ions to alleviate the impairment of angiogenesis. Therefore, we hypothesized that MT2A could promote angiogenesis in chronically ischemic brains by neutralizing excessive copper ions during copper overload (CPO).MethodsWe first collected dura matter (DM) samples from CICD patients and examined the expression of cuproptosis-related genes (DLAT, FDX1, and SDHB) to confirm the inhibitory effect of CPO on angiogenesis. Then, we treated human umbilical vein endothelial cells (HUVECs) with different concentrations of elesclomol and CuCl2 to determine the optimal concentration for inducing CPO. HUVEC activity and mitochondrial structure and function were detected to explore the ability of MT2A to alleviate CPO-induced damage. Finally, a rat model of 2-vessel occlusion plus encephalo-myo-synangiosis (2VO + EMS) with CPO was established to test the proangiogenic effect of MT2A through the copper–mitochondria regulatory mechanism in chronically ischemic brains.ResultsCompared with those from Matsushima grade A patients, DM samples from Matsushima grade C patients presented significantly greater DLAT and FDX1 expression and significantly lower SDHB expression. The optimal drug concentration for inducing CPO was subsequently determined, and in vitro experiments revealed that HUVEC activity was significantly decreased in the CPO group under hypoxic culture, accompanied by increased DLAT oligomerization, decreased SDHB expression, increased HSP70 expression. Moreover, significantly more common mitochondrial aberrations and significantly lower mitochondrial activity were detected in the CPO group compare with the control group. Additionally, MT2A overexpression alleviated CPO-induced mitochondrial dysfunction and cytotoxicity, improving HUVEC viability. In vivo, a CPO rat model was established, and CPO inhibited cerebral angiogenesis in 2VO + EMS model rats. Moreover, significantly greater CD31 expression, less DLAT accumulation, more mitochondria, and fewer mitochondrial abnormalities were observed in the CPOMT2A+ group than in the CPO group, accompanied by significantly improved cerebral blood perfusion and cognitive function.ConclusionMT2A can promote angiogenesis in chronically ischemic brains by neutralizing excessive copper ions and rescuing CPO-induced mitochondrial dysfunction.

An alumina-modified glassy carbon electrode: a robust platform for accurate nimodipine detection in pharmaceutical applications.

Nimodipine (NMP) is a calcium channel blocker known for maintaining blood perfusion, particularly in the brain. Given its importance and widespread applicability, tracking NMP during industrial processes for both pharmaceutical dosage forms and raw material samples is crucial. This article discusses the use of a glassy carbon electrode (GCE) polished with commercial alumina for NMP determination. Atomic force microscopy (AFM) confirmed the presence of residual alumina on the surface of the GCE, and electrochemically active surface area (EASA) analysis demonstrated an enhancement in the active area. The alumina-polished electrode (GCE/AP) exhibited a superior response for NMP, with voltammograms obtained via differential pulse voltammetry (DPV). In this investigation, we employed density functional theory (DFT) calculations to examine the electrochemical characteristics of NMP from a theoretical standpoint. The geometry was optimized by employing the Generalized Gradient Approximation (GGA) functional, BP86, in conjunction with the Def2-TZVPPPD basis set and D3BJ dispersion corrections. To identify potential sites for oxidation and reduction, Fukui indices and dual descriptors were employed. The results indicate that the nitro group is the most probable site for reduction, whereas the dihydropyridine ring displays a proclivity for electrophilic attack. Regarding electroanalysis, two calibration curves were established through consecutive additions of NMP, with linear ranges of 0.20 to 49.0 μmol L-1 and 2.92 to 13.5 μmol L-1, respectively. The theoretical limits of detection (LOD) and quantification (LOQ) were, respectively, 0.06 μmol L-1 and 0.20 μmol L-1 for the first curve, and 4.0 μmol L-1 and 12.0 μmol L-1 for the second curve. Common constituents in pharmaceutical tablets were tested as potential interferents, and GCE/AP showed acceptable anti-interference ability. NMP was successfully quantified in tablet and raw material samples using the novel electrochemical method and High-Performance Liquid Chromatography (HPLC). Statistical analysis revealed no significant differences between the results. This confirms that the GCE/AP sensor was effectively applied to pharmaceutical samples, consistent with findings reported in the literature.

Heat Stress and Its Impact on Corpus Luteum (CL) Function and Reproductive Efficiency in Mammals: A Critical Review.

Heat stress is considered as one of the most crucial environmental stressors affecting reproductive efficiency in mammals through modulation of the function of Corpus Luteum (CL) that plays a vital role in progesterone production and pregnancy maintenance. Therefore, this detailed systematic review seeks to bring forward the interdisciplinary perspectives on the impact of heat stress exposure on CL function regarding hormonal shift, luteal phase distortion and fertility receptivity. High temperatures are shown to impose oxidative stress, change blood perfusion within the CL, signal transduction which converts the signal from the signaling molecule into an intracellular reaction and impaired luteal activity. This review incorporates various scientific studies on these effects to different mammalian species concerning the associated physiological mechanisms. Besides this, it also considers the overall impact in warm stressed population in livestock breedingin the agricultural system as well as their conservation from a general perspective. Some of the prevention and control measures for heat related reproductive problems are also covered here, addressing the importance of finding the impact on the CL in order to put in place these interventions. This review may be used to inform future developments that may improve the CL function with regards to heat stress and possible solutions to help mammals reproduced under climate change tender environment and even rising temperatures globally.

Assessment of Treatment Effects of Aminaphtone by Capillaroscopy in a Patient with Raynaud’s Phenomenon

Background: Aminaphtone is a well-established pharmaceutical agent that has been utilized for over 40 years, primarily due to its effectiveness in treating microvascular disorders. Recent studies have explored its impact on various conditions, including chronic venous insufficiency, diabetic microangiopathy, leg ulcers, systemic sclerosis, and Raynaud’s phenomenon. These investigations have consistently demonstrated that aminaphtone enhances skin blood perfusion and mitigates endothelial damage, all while maintaining a robust safety profile over time. Case Summary: This report highlights the potential of aminaphtone in improving microcirculation in a young patient who experienced spontaneous capillary rupture in her second finger. A 38-year-old woman with undifferentiated connective tissue disease presented to the clinic for periungual videocapillaroscopy (NVC). Given the microangiopathic changes observed during the NVC, she was prescribed aminaphtone. After seven months of treatment, a follow-up NVC revealed significant improvement in the capillaroscopic findings. A comprehensive literature review on aminaphtone was conducted using electronic databases (PUBMED, Google Scholar, ResearchGate, UpToDate), along with manual searches, focusing on articles published until November 2024. Conclusion: Treatment with aminaphtone led to notable improvements in microangiopathic health. Following the introduction of this medication, the nailfold microvascular bed, which previously exhibited severe alterations, showed a remarkable transition to only mild abnormalities.

Association of Lactate Levels and Mortality in Intensive Care Units

Most critically ill patients experience hemodynamic disorders that cause a decrease in blood perfusion, resulting in hypoxia that can increase lactate production. This study will examine the relationship between lactate levels and mortality in intensive care. This study uses a quantitative observational analytical method with a cross-sectional study design and using medical record data. Data analysis was carried out using an Independent T-test to see if there was a significant difference between lactate levels in the blood of dead and living subjects. This study, 154 subjects were obtained, consisting of 96 males (62.3%) and 58 females (37.7%). The average lactate level in the death group was 3.99, and the live group was 2.4 (p=0.004). Subjects with higher lactate levels have higher mortality rates. Lactate levels are one of the indicators of tissue oxygenation in critically ill patients. Hyperlactatemia is common in critically ill patients and can reflect an imbalance between local or systemic oxygen delivery and demand. Hyperlactatemia can cause lactic acidosis or metabolic acidosis and is associated with high mortality outcomes. Increased lactate levels are also associated with the development of Multiple Organ Dysfunction Syndrome (MODS). Subjects with high lactate levels are often associated with a variety of etiologies and poor prognosis, especially critical patients in the Intensive Care Unit (ICU). There was a relationship between blood lactate levels and mortality in ICU patients.

Stem Cell–Based Therapies via Different Administration Route for Stroke: A Meta-analysis of Comparative Studies

Stroke, a neurological condition from compromised cerebral blood perfusion, remains a major global cause of mortality and disability. Conventional therapies like tissue plasminogen activator are limited by narrow therapeutic windows and potential adverse effects, highlighting the urgency for novel treatments. Stem cell–based therapies, with their neuroprotective and regenerative properties, present a promising yet highly diverse alternative. By conducting literature search and data extraction from the PubMed, Embase, and Cochrane databases, this meta-analysis assessed the clinical efficacy and safety of stem cell–based therapies administered via intravenous (IV) and non-IV routes in 17 studies with stroke patients. Primary outcomes included the National Institute of Health Stroke Scale (NIHSS), Barthel Index (BI), and modified Rankin Scale (mRS), while secondary outcomes included mortality and adverse events. Results demonstrated significant improvements in NIHSS, BI, and mRS scores, particularly in non-IV groups within 6- and 12-month follow-ups, suggesting delayed but enhanced therapeutic efficacy. Mortality was reduced in both IV and non-IV groups, indicating treatment safety. Adverse events, categorized into neurological and systemic complications, showed no significant differences between intervention and control groups, further emphasizing the safety of stem cell therapies. Non-IV routes showed more long-term benefits, potentially due to enhanced cell delivery and integration. These findings demonstrate the potential of stem cell therapies to improve functional recovery and survival in stroke patients, regardless of administration route. However, the delayed response underscores the need for extended follow-up in clinical applications. Further research is required to standardize treatment protocols, optimize cell types and doses, and address patient-specific factors to integrate stem cell therapies into routine clinical practice.

Understanding the relationship between silicone implants, tumor antigens, and breast cancer risk: An immunological study in rats.

This study aimed to investigate the effects of silicone implants on the incidence of breast cancer in rats, as well as their impact on immune surveillance mechanisms. Female SD rats were divided into three groups: a Placebo Surgery Group (PSG), a Thoracic Implant Group (TIG), and a Back Implant Group (BIG). Following the corresponding surgical procedures, we measured Secretoglobin Family 2A, Member 2(SCGB2A2) and Mucin-1 (MUC1) antigen levels using ELISA, and statistical analyses were conducted to evaluate immune responses. The N-Methyl-N-Nitrosourea(MNU)-induced breast cancer model and pathological analyses indicated that the incidence of breast cancer in the thoracic implant group was lower, suggesting that silicone implants may reduce the risk of breast cancer. Additionally, laser speckle blood flow imaging and immunohistochemical analysis revealed blood perfusion in the implant capsule area and an active response of immune cells, indicating that immune surveillance may exert local effects. These findings provide the first evidence of a relationship between tumor antigens, silicone implants, and breast cancer incidence, offering a new immunological perspective on the safety of silicone implants.

Computational exploration of injection strategies for improving medicine distribution in the liver.

The liver, a vital metabolic organ, is always susceptible to various diseases that ultimately lead to fibrosis, cirrhosis, acute liver failure, chronic liver failure, and even cancer. Optimal and specific medicine delivery in various diseases, hepatectomy, shunt placement, and other surgical interventions to reduce liver damage, transplantation, optimal preservation, and revival of the donated organ all rely on a complete understanding of perfusion and mass transfer in the liver. This study aims to simulate the computational fluid dynamics of perfusion and the temporal-spatial distribution of a medicine in a healthy liver to evaluate the hemodynamic characteristics of flow and medicine transport with the purpose of more effective liver treatment. Patient-specific geometries of parenchyma and hepatic artery, portal vein, and hepatic vein vessels of a healthy liver were segmented and reconstructed from the abdominal computed tomography scan images. Mesh was generated for the comprehensive combined model using unstructured tetrahedral elements. Transient pressure values were applied as boundary conditions at the portal vein and hepatic artery inlets, and pressure outlet boundary condition was assumed at the hepatic vein outlet. Medicine injection was done through the portal vein. The liver parenchyma was assumed to be a porous medium. Finally, computational fluid dynamics (CFD) simulation was performed to investigate blood perfusion, medicine distribution, and saturation time. The velocity parameter values calculated for the hepatic artery, portal vein, and hepatic vein vessels were consistent with the physiological ranges. The mass flow rate was higher in the portal vein than in the hepatic artery, which was consistent with high perfusion through the portal vein. The portal pressure gradient was 8.53mmHg. From a pharmacokinetic viewpoint, medicine distribution in porous tissue was a heterogeneous process. Medicine distribution was higher at end-diastolic pressure than at peak-systolic pressure which showed the influence of hepatic artery flow. The tissue was saturated faster at first 40s and with decreasing porosity, saturation time decreased, and distribution improved. The right lobe included a higher number of vascular terminals due to its larger volume, and the flow rate was higher in this lobe compared to the left lobe. This showed the significant effect of the right lobe on the overall function of the body. Recirculation flow zones along hepatic artery and portal vein branches emphasized the sensitivity of downstream vessels. Rotational flow and potential vortex formation at the hepatic vein outlet may indicate a risk of plaque and clot formation in this region. The heterogeneous distribution of medicine indicated the importance of injection time in treating liver diseases. The percentage of tissue porosity affected the saturation time, so adjusting the medicine dose and injection time could be challenging in treatments.

Numerical Simulation of Fluid-Structure Interaction in Axillary Artery Venoarterial Extracorporeal Membrane Oxygenation for Heart Failure Patients.

Although axillary artery venoarterial extracorporeal membrane oxygenation (VA-ECMO) has been utilized as a mechanical circulatory support for patients with end-stage heart failure (HF), there is currently insufficient evidence to support its effectiveness and safety. The objective of this study was to analyze the hemodynamic effects of axillary artery VA-ECMO. To this end, we obtained CT angiographic imaging data of the aorta from a carefully selected heart failure patient with a cardiac output of 2.1 L/min. These data were used to construct a detailed fluid-structure interaction model of the aorta. Axillary artery VA-ECMO was then simulated within this model, maintaining a constant flow rate of 3 L/min. The intra-aortic balloon counterpulsation (IABP) balloon was simulated to inflate and deflate in synchrony with the diastolic and systolic phases of the cardiac cycle. Hemodynamic effects, including left ventricular (LV) pressure afterload, vessel wall stress, perfusion of vital organs, blood flow pulsatility, and the watershed region, were calculated using fluid-structure interaction analysis. We found that axillary artery VA-ECMO delivers well-distributed, oxygen-rich blood flow but may increase left ventricular (LV) afterload and reduce cerebral blood flow. However, when combined with IABP, it unloads LV pressure and increases cerebral blood flow. Integrating axillary artery VA-ECMO with IABP can promote cardiac function recovery and improve oxygen-rich blood perfusion to the vital organs of heart failure patients.

Antiangiogenic therapy with recombinant human endostatin may improve blood perfusion of cervical node with necrosis in nasopharyngeal carcinoma patients: a preliminary study by using contrast-enhanced ultrasound

Antiangiogenic therapy with recombinant human endostatin may improve blood perfusion of cervical node with necrosis in nasopharyngeal carcinoma patients: a preliminary study by using contrast-enhanced ultrasound

COMPUTED TOMOGRAPHY CEREBRAL PERFUSION TO PREDICT FUNCTIONAL OUTCOME IN PAEDIATRIC HEAD INJURY: A COMPARITIVE STUDY OF VOXEL BASED AND WHOLE BRAIN PERFUSION.

This study evaluates the extent of perfusion abnormalities in pediatric traumatic head injury patients by using computed tomography perfusion (CTP) and compares the efficacy of voxel based and whole brain perfusion data clinically with functional outcome scales GOSE-P and MRS. In this Prospective study 100 eligible patients of age group 0-15 years were enrolled. Subjects were categorized into mild, moderate and severe traumatic brain injury using GCS.CT perfusion scans were performed at admission and at time of discharge. Both voxel-based and whole brain perfusion data were acquired at five regions of interest: orbitofrontal cortex, internal capsule, thalamus, caudate nucleus, and sensorimotor cortex for cerebral blood perfusion. The extent of perfusion abnormalities were noted in CTP scans. GOSE-P and MRS were utilised to clinically evaluate functional outcomes. Significant differences in CT perfusion findings between voxel-based and whole brain approaches were noted. Voxel-based scans demonstrated superior predictive value in severe cases, while whole brain scans were promising in moderate cases. GCS scores and specific CT parameters (CBF AND MTT) were also significant predictors of outcomes. The comparative analysis highlights the complementary roles of voxel-based and whole brain perfusion CT in predicting functional outcomes in pediatric head injury cases. Clinicians should consider both approaches when evaluating cerebral perfusion status and making treatment decisions. Further research is warranted to validate these findings and refine imaging protocols to optimize predictive accuracy in this vulnerable population.

Functional MRI study of neurovascular coupling in patients with non-lesional epilepsy.

The diagnosis of patients with non-lesional epilepsy (NLE) is relatively challenging because of the absence of a clear focus on imaging, and the underlying pathological mechanism remains unclear. The neuronal activity and functional connectivity of NLE patients are significantly abnormal, and the neuronal activity of epilepsy patients is closely related to cerebral blood flow (CBF). Neurovascular coupling (NVC) offers insights into the relationship between neuronal activity and CBF. Hence, we intend to explore the alterations of NVC in NLE patients and their influences on cognitive function. Clinical data of 24 patients with NLE (15 female; age range 19-40 years; median age 30.5 years) and 39 healthy controls (27 female; age range 19-40 years; median age 30 years) were collected, and resting-state functional magnetic resonance imaging (rs-fMRI) and 3D arterial spin labeling (ASL) were performed. The imaging indexes of amplitude of low-frequency fluctuation (ALFF) and CBF were calculated, respectively, by post-processing analysis. The differences in CBF, ALFF and CBF/ALFF ratio between the two groups were analyzed, along with correlation with clinical data of NLE patients. Compared with the healthy controls, the CBF of the right parahippocampal gyrus was significantly decreased, and the CBF/ALFF ratio of the right inferior parietal, but supramarginal and angular gyri was significantly increased in NLE patients (p < 0.001). Moreover, the CBF/ALFF ratio was positively correlated with epilepsy depression score (r = 0.546, p = 0.006). NLE patients showed abnormal local NVC, which was associated with the severity of depression. The combined application of rs-fMRI and ASL can comprehensively evaluate the neuronal activity and cerebral blood perfusion in patients with NLE. The abnormal NVC is of great significance for us to explore the central mechanism of the occurrence and development of NLE.

Effect of ultrasound combined with microbubbles therapy on tumor hypoxic microenvironment.

Tumor tissues exhibit significantly lower oxygen partial pressure compared to normal tissues, leading to hypoxia in the tumor microenvironment and result in resistance to tumor treatments. Strategies to mitigate hypoxia include enhancing blood perfusion and oxygen supply, for example,by decomposing hydrogen peroxide within the tumor. Improving hypoxia in the tumor microenvironment could potentially improve the efficacy of cancer treatments. Previous studies have demonstrated that ultrasound of appropriate intensity when combined with microbubbles, can improve tumor blood perfusion. However, its effects on tumor hypoxia remain unclear. This study aimed to assess the effects of low-frequency non-focused ultrasound combined with microbubbles at different intensities on tumor microenvironment hypoxia and to identify the optimal ultrasound parameters for alleviating tumor hypoxia. Rabbits with VX2 tumors received ultrasound and microbubble treatments at different acoustic pressures and pulse repetition frequencies. The changes in tumor tissue blood perfusion before and after treatment were observed by contrast enhanced ultrasound (CEUS). The changes in tumor tissue hypoxia before and after treatment were observed by measuring oxygen partial pressure directly with in tumor tissue and immunohistochemical staining for hypoxia-inducible factor-1α (HIF-1α). Results indicated that low frequency, non-focused ultrasound at 0.5MPa/20Hz and 0.5MPa/40Hz, when combined with microbubbles, could increase tumor tissue blood perfusion and improve the hypoxia in tumor tissues. This study provides a new method for improving hypoxia in the tumor microenvironment (TME) which could potentially improve the cancer treatments resistance.

Indocyanine green fluorescence-guided laparoscopic central pancreatectomy for complete pancreatic transection trauma: a rare case and literature review.

Pancreatic trauma is a rare solid organ injury. Conservative treatment is often indicated in patients with no pancreatic duct injury, while patients with high-grade pancreatic damage most often require surgical intervention. Laparoscopic central pancreatectomy (LCP) is a parenchyma-sparing approach and can prevent endocrine and exocrine insufficiency after pancreatic resection. Indocyanine green (ICG) fluoroscopy can help the surgeon assess the blood supply of the target organ. The case we describe here is a 33-year-old male patient who was transferred to our hospital due to blunt abdominal trauma caused by a car accident. The patient was hemodynamically stable on admission and was diagnosed with isolated pancreatic trauma by a multidisciplinary team that included radiologists, emergency physicians, and pancreatic surgeons. The patient then underwent emergency laparoscopic central pancreatectomy, during which we used ICG fluoroscopy to assess the blood perfusion of the damaged pancreas to determine the extent of resection. The patient developed a biochemical fistula (grade A pancreatic fistula) after surgery, and no other intervention was performed except for continuous drainage. The patient was discharged on postoperative day 13. At the 3-month follow-up, the patient did not present any clinical manifestations of pancreatic endocrine and exocrine insufficiency. To the best of our knowledge, there have been no reports of ICG-guided emergency LCP for blunt abdominal trauma. In selected patients, emergency LCP is feasible and should be supported by a multidisciplinary team and performed by an experienced pancreatic surgeon with advanced laparoscopic skills.

Characterizing astrocyte-mediated neurovascular coupling by combining optogenetics and biophysical modeling.

Vasoactive signaling from astrocytes is an important contributor to the neurovascular coupling (NVC), which aims at providing energy to neurons during brain activation by increasing blood perfusion in the surrounding vasculature. Pharmacological manipulations have been previously combined with experimental techniques (e.g., transgenic mice, uncaging, and multiphoton microscopy) and stimulation paradigms to isolate in vivo individual pathways of the astrocyte-mediated NVC. Unfortunately, these pathways are highly nonlinear and non-additive. To separate these pathways in a unified framework, we combine a comprehensive biophysical model of vasoactive signaling from astrocytes with a unique optogenetic stimulation method that selectively induces astrocytic Ca2+ signaling in a large population of astrocytes. We also use a sensitivity analysis and an optimization technique to estimate key model parameters. Optogenetically-induced Ca2+ signals in astrocytes cause a cerebral blood flow (CBF) response with two major components. Component-1 was rapid and smaller (ΔCBF∼13%, 18 seconds), while component-2 was slowest and highest (ΔCBF ∼18%, 45 seconds). The proposed biophysical model was adequate in reproducing component-2, which was validated with a pharmacological manipulation. Model's predictions were not in contradiction with previous studies. Finally, we discussed scenarios accounting for the existence of component-1, which once validated might be included in our model.

An eCIRP inhibitor attenuates fibrosis and ferroptosis in ischemia and reperfusion induced chronic kidney disease

BackgroundChronic kidney disease (CKD) is a leading cause of death in the United States, and renal fibrosis represents a pathologic hallmark of CKD. Extracellular cold-inducible RNA-binding protein (eCIRP) is a stress response protein involved in acute inflammation, tissue injury and regulated cell death. However, the role of eCIRP in chronic inflammation and tissue injury has not been elucidated. We hypothesize that eCIRP is involved in renal ischemia/reperfusion (RIR)-induced CKD and that C23, an antagonist to eCIRP, is beneficial in attenuating renal fibrosis and ferroptosis in RIR-induced CKD.MethodsC57BL/6 (WT) or CIRP−/− mice underwent renal injury with total blockage of blood perfusion by clamping bilateral renal pedicles for 28 min. In the WT mice at the time of reperfusion, they were treated with C23 (8 mg/kg) or vehicle. Blood and kidneys were harvested for further analysis at 21 days thereafter. In a separate cohort, mice underwent bilateral RIR and treatment with C23 or vehicle and were then subjected to left nephrectomy 72 h thereafter. Mice were then monitored for additional 19 days, and glomerular filtration rate (GFR) was assessed using a noninvasive transcutaneous method.ResultsIn the RIR-induced CKD, CIRP−/− mice showed decreased collagen deposition, fibronectin staining, and renal injury as compared to the WT mice. Administration of C23 ameliorated renal fibrosis by decreasing the expression of active TGF-β1, α-SMA, collagen deposition, fibronectin and macrophage infiltration to the kidneys. Furthermore, intervention with C23 significantly decreased renal ferroptosis by reducing iron accumulation, increasing the expression of glutathione peroxidase 4 (GPX4) and lipid peroxidation in the kidneys of RIR-induced CKD mice. Treatment with C23 also attenuated BUN and creatinine. Finally, GFR was significantly decreased in RIR mice with left nephrectomy and C23 treatment partially prevented their decrease.ConclusionOur data show that eCIRP plays an important role in RIR-induced CKD. Treatment with C23 decreased renal inflammation, alleviated chronic renal injury and fibrosis, and inhibited ferroptosis in the RIR-induced CKD mice.

Short Supply of High Levels of Guanidine Acetic Acid, Alters Ovarian Artery Flow and Improves Intraovarian Blood Perfusion Area Associated with Follicular Growth in Sheep.

Guanidinoacetic acid (GAA), a precursor of creatine, has a recognized effect on ruminant performance when used as a dietary supplement. However, its impact on reproductive response remains to be elucidated. Therefore, this study aimed to contribute initially to this area by supplementing the diets of ewes with a high dose of GAA, evaluating its effects on reproductive response. Twenty adult sheep had their estrus synchronized using an MPA sponge, eCG, and PGF2α. After estrus detection ewes were mated. For 10 days until mating, ewes were grouped in groups of baseline diet (BSD; n = 10) and GAA diet (GAAD; n = 10), which was the BSD with daily 0.9 g/kg DM of GAA. After the eCG + PGF2α dose, the GAAD group exhibited an increase in the peak diastolic and pulsatility of the ovarian artery, a reduction in the systolic/diastolic peaks ratio, and a larger intraovarian blood perfusion area. A greater depletion of follicles with <3 mm was observed in the GAAD group and a higher number of follicles ≥3 mm. No differences were observed between the diets respect to pregnancy, and twin rates. Thus, a high GAA supply before mating significantly alters ovarian vasculature and improves follicular growth in ewes but does not affect the pregnancy rate.

Axial length to corneal curvature radius ratio is negatively correlated with choroidal blood flow in myopic children.

The pathophysiologic mechanisms underlying early-onset myopia remain unclear; in this study, we investigate the pathogenesis by examining the interrelationships between axial length to corneal curvature radius ratio ( ) and choroidal blood flow. This cross-sectional study included 202 eyes from myopic children, categorized into 141 eyes with mild myopia, 47 eyes with moderate myopia, and 14 eyes with high myopia. Optical coherence tomography angiography (OCTA) was used to measure choroidal blood flow perfusion within a 6mm × 6mm area of the macular region, divided into nine subareas based on ETDRS partitioning: macular fovea, nasal side 1, superior 1, temporal side 1, inferior 1, nasal side 2, superior 2, temporal side 2, and inferior 2. Data on corneal curvature and ocular axial length were collected to calculate the , with equivalent spherical lens power, gender, and age gathered for group comparisons, and the correlation between AL/CR and choroidal blood flow perfusion volume was analyzed. was significantly negatively correlated with choroidal blood flow perfusion ( ). Linear regression and mediation analyses indicated that for each unit increase in choroidal blood perfusion volume in nasal region 1, decreased by an average of 0.421 units. This relationship is mediated by several factors, with axial length serving as a key mediator. correlates with choroidal blood flow perfusion, indicating a link between refractive biological parameters and ocular blood circulation. Myopia is an ischemic eye condition that warrants attention to fundus microcirculation changes in myopic children.

Ultrasound stimulated perfluorobutane microbubbles cavitation enhanced the therapeutic effect of colchicine in rats with acute gouty arthritis.

This study aimed to explore whether cavitation generated by ultrasound-stimulated microbubbles (USMB) can enhance the therapeutic efficacy of colchicine and diminish its gastrointestinal side effects in rats with acute gouty arthritis (AGA). The rat AGA model was established by injection of Monosodium urate (MSU) crystals. The rats were randomly divided into 6 groups (A: control group, B: model control group, C: cavitation group, D: high dose colchicine group, E: cavitation+low dose colchicine group, F: cavitation+high dose colchicine group) according to whether they were given cavitation and different doses of colchicine. The effect of cavitation on blood perfusion was analyzed by comparing contrast-enhanced ultrasound (CEUS) and the area under the curve (AUC) of CEUS with the ankle joint of right hind limb. The AGA symptoms were assessed by referring to the degree of ankle joint swelling within 24h and the gait score. The infiltration of neutrophils was determined using the hematoxylin-eosin (HE) staining method. For the evaluation of vascular inflammation and dilation, plasma interleukin-1β (IL-1β) and endothelial nitric oxide synthase (eNOS) served as the key indicators. Besides, the severity of gastrointestinal adverse reactions is determined by analyzing the gastrointestinal reaction scores. When compared with groups A, B, and D, the AUC was markedly higher in groups C, E, and F (all P<0.05). In groups E and F, the degree of ankle swelling, gait scores, and the level of plasma IL-1β in AGA rats were lower, while the concentration of plasma eNOS was higher compared to the group D (all P<0.05). HE staining findings demonstrated that the integration of cavitation and colchicine played a positive role in reducing neutrophil infiltration in the ankle joint synovium and mitigating the gastrointestinal reaction score in AGA rats. In contrast to groups D, E, and F that were given colchicine, group E had a substantially lower gastrointestinal reaction score, with statistically significant differences observed in pairwise comparisons (all P<0.05). In rats with AGA, cavitation generated by USMB exerted a remarkable effect on augmenting the blood perfusion of the ankle joint. This, in turn, not only amplified the anti-gout efficacy of colchicine but also reduced the dosage of colchicine. Concurrently, it effectively mitigated the associated gastrointestinal side effects.

Circulating factors, in both donor and ex-vivo heart perfusion, correlate with heart recovery in a pig model of DCD

BackgroundHeart transplantation with donation after circulatory death and ex-situ heart perfusion offers excellent outcomes and increased transplantation rates. However, improved graft evaluation techniques are required to ensure effective utilization of grafts. Therefore, we investigated circulating factors, both in-situ and ex-situ, as potential biomarkers for cardiac graft quality. MethodsCirculatory death was simulated in anesthetized male pigs with warm ischemic durations of 0, 10, 20, or 30 min. Hearts were explanted and underwent ex-situ perfusion for 3h in an unloaded mode, followed by left ventricular loading for 1h, to evaluate cardiac recovery (outcomes). Multiple donor blood and ex-situ perfusate samples were used for biomarker evaluation with either standard biochemical techniques or nuclear magnetic resonance spectroscopy. ResultsCirculating adrenaline, both in the donor and at 10 min ex-situ heart perfusion, negatively correlated with cardiac recovery (p <0.05 for all). We identified several new potential biomarkers for cardiac graft quality that can be measured rapidly and simultaneously with nuclear magnetic resonance spectroscopy. At multiple timepoints during unloaded ex-situ heart perfusion, perfusate levels of acetone, betaine, creatine, creatinine, fumarate, hypoxanthine, lactate, pyruvate and succinate (p <0.05 for all) significantly correlated with outcomes; the optimal timepoint being 60 min. ConclusionsIn heart donation after circulatory death, circulating adrenaline levels are valuable for cardiac graft evaluation. Nuclear magnetic resonance spectroscopy is of particular interest, as it measures multiple metabolites in a short timeframe. Improved biomarkers may allow more precision and therefore better support clinical decisions about transplantation suitability.