Insufficient Blood Flow Research Articles

Identification of CD141+vasculogenic precursor cells from human bone marrow and their endothelial engagement in the arteriogenesis by co-transplantation with mesenchymal stem cells

BackgroundCritical limb ischemia (CLI) is a condition characterized by insufficient blood flow to the lower limbs, resulting in severe ischemia and potentially leading to amputation. This study aims to identify novel vasculogenic precursor cells (VPCs) in human bone marrow and evaluate their efficacy in combination with bone marrow-derived mesenchymal stem cells (BM-MSCs) for the treatment of CLI.MethodsEx vivo cultured VPCs and BM-MSCs from bone marrow were characterized and their effects on neovascularization and long-term tissue regeneration were tested in a mouse CLI model.ResultsVPCs, expressing high levels of hepatocyte growth factor and c-MET, were identified from human bone marrow aspirates. These cells exhibited strong vasculogenic capacity in vitro but possessed a cellular phenotype distinct from those of previously reported endothelial precursor cells in circulation or cord blood. They also expressed most surface markers of BM-MSCs and demonstrated multipotent differentiation ability. Screening of 376 surface markers revealed that VPCs uniquely display CD141 (thrombomodulin). CD141+VPCs are present in BM aspirates as a rare population and can be expanded ex vivo with a population doubling time of approximately 20 h, generating an elaborate vascular network even under angiogenic factor-deficient conditions and recruiting BM-MSCs to the network as pericyte-like cells. Intramuscular transplantation of a combination of human CD141+VPCs and BM-MSCs at a ratio of 2:1 resulted in limb salvage, blood flow recovery, and regeneration of large vessels in the femoral artery-removed CLI model, with an efficacy superior to that of singular transplantation. Importantly, large arteries and arterioles in dual cell transplantation expressed human CD31 in the intima and human α-smooth muscle actin in media layer at 4 and 12 weeks, likely indicating their lineage commitment to endothelial cells and vascular smooth muscle, respectively, in vivo.ConclusionDual-cell therapy using BM-derived CD141+ VPCs and BM-MSCs holds potential for further development in clinical trials to treat peripheral artery disease and diabetic ulcers.

Understanding perioperative risk determinants in carotid endarterectomy: the impact of compromised circle of Willis morphology on inter-hemispheric blood flow indices based on intraoperative internal carotid artery stump pulse pressure and backflow patterns.

Carotid artery stenosis (CAS) often requires surgical intervention through carotid endarterectomy (CEA) to prevent stroke. Accurate cerebrovascular risk assessments are crucial in CEA, as poor collateral circulation can lead to insufficient interhemispheric blood flow compensation, resulting in ischemic complications. Therefore, understanding perioperative risk determinants is vital. This study aims to determine the impact of compromised circle of Willis (CoW) morphology on inter-hemispheric blood flow, focusing on indices based on intraoperative internal carotid artery stump pulse pressure and backflow patterns. In 80 CAS patients who underwent CEA, preoperative CT angiography for CoW was conducted. Patients were categorized into five subgroups based on their CoW anatomy and three additional groups based on intraoperative internal carotid artery (ICA) stump backflow patterns evaluated by the surgeon. Continuous blood pressure signals, including systolic, diastolic, mean, and pulse pressure values, were recorded during the procedure. The relationship between CoW anatomical variants and the systolic and diastolic segments of the averaged pressure waveforms, particularly diastolic pressure decay, was analyzed. The correlation between CoW anatomy and stump backflow intensity was also examined. Significant variability in ICA stump backflow and pressure values was evident across CoW variants. Patients with compromised CoW morphology exhibited weaker backflow patterns and lower ICA stump pulse pressure values, consistent with impaired interhemispheric blood flow. Notably, ICA stump diastolic pressure decay was consistent across most CoW variant groups, indicating developed collateral circulation in cases with CoW anomalies. Thus, impaired CoW integrity is associated with compromised interhemispheric blood flow indices based on intraoperative ICA stump pulse pressure and backflow patterns during CEA. Integrating intraoperative pulse waveform analysis with preoperative CT angiography provides a more detailed assessment of cerebrovascular risk, guiding the selective use of shunts. This combined approach may improve surgical outcomes and patient safety by identifying patients at increased risk of perioperative neurological events due to CoW anomalies.

A novel technique for pancreatic juice drainage to the remaining graft duodenum after blood reperfusion in pancreas transplantation

TechniqueIn pancreatic transplantation, during bench surgery, the oral and anal sides of a graft duodenum are cut with linear staplers to be as short as possible in order to ascertain blood flow to the graft duodenum stumps. However, this can lead to a distended graft duodenum owing to the large amount of pancreatic juice produced after blood reperfusion during the recipient operation. Controlling bleeding after blood reperfusion and ensuring complete hemostasis are difficult due to obstructed vision caused by the distended graft duodenum. Additionally, the edematous mucosa due to the distended graft duodenum makes it difficult to anastomose the graft duodenum to the recipient's small intestine. Herein, we developed a novel technique during bench surgery to overcome these disadvantages of a distended graft duodenum, by initially leaving the anal side of the graft duodenum uncut to drain the produced pancreatic juice following blood reperfusion. After confirming the hemostasis and anastomosing the graft duodenum to the small intestine, the anal side of the graft duodenum is cut with a linear stapler at the point where sufficient blood flow is confirmed based on duodenal color. ResultsThis technique enables us to concentrate on the hemostasis and anastomosis without attending to the distended graft duodenum. Furthermore, stump issues due to insufficient blood flow can be avoided. ConclusionThis pancreatic juice drainage technique in pancreas transplantation can be useful to reduce postoperative complications.

PLEKHG1: New Potential Candidate Gene for Periventricular White Matter Abnormalities.

Hypoxic-ischemic brain damage presents a significant neurological challenge, often manifesting during the perinatal period. Specifically, periventricular leukomalacia (PVL) is emerging as a notable contributor to cerebral palsy and intellectual disabilities. It compromises cerebral microcirculation, resulting in insufficient oxygen or blood flow to the periventricular region of the brain. As widely documented, these pathological conditions can be caused by several factors encompassing preterm birth (4-5% of the total cases), as well single cotwin abortion and genetic variants such as those associated with GTPase pathways. Whole exome sequencing (WES) analysis identified a de novo causative variant within the pleckstrin homology domain-containing family G member 1 (PLEKHG1) gene in a patient presenting with PVL. The PLEKHG1 gene is ubiquitously expressed, showing high expression patterns in brain tissues. PLEKHG1 is part of a family of Rho guanine nucleotide exchange factors, and the protein is essential for cell division control protein 42 (CDC42) activation in the GTPase pathway. CDC42 is a key small GTPase of the Rho-subfamily, regulating various cellular functions such as cell morphology, migration, endocytosis, and cell cycle progression. The molecular mechanism involving PLEKHG1 and CDC42 has an intriguing role in the reorientation of cells in the vascular endothelium, thus suggesting that disruption responses to mechanical stress in endothelial cells may be involved in the formation of white matter lesions. Significantly, CDC42 association with white matter abnormalities is underscored by its MIM phenotype number. In contrast, although PLEKHG1 has been recently associated with patients showing white matter hyperintensities, it currently lacks a MIM phenotype number. Additionally, in silico analyses classified the identified variant as pathogenic. Although the patient was born prematurely and subsequently to dichorionic gestation, during which its cotwin died, we suggest that the variant described can strongly contribute to PVL. The aim of the current study is to establish a plausible association between the PLEKHG1 gene and PVL.

2,3-Diphosphoglyceric Acid Alleviating Hypoxic-Ischemic Brain Damage through p38 MAPK Modulation.

Neonatal hypoxic-ischemic encephalopathy (HIE) is a critical condition characterized by significant brain damage due to insufficient blood flow and oxygen delivery at birth, leading to high rates of neonatal mortality and long-term neurological deficits worldwide. 2,3-Diphosphoglyceric acid (2,3-DPG), a small molecule metabolite prevalent in erythrocytes, plays an important role in regulating oxygen delivery, but its potential neuroprotective role in hypoxic-ischemic brain damage (HIBD) has yet to be fully elucidated. Our research reveals that the administration of 2,3-DPG effectively reduces neuron damage caused by hypoxia-ischemia (HI) both in vitro and in vivo. We observed a notable decrease in HI-induced neuronal cell apoptosis, attributed to the downregulation of Bax and cleaved-caspase 3, alongside an upregulation of Bcl-2 expression. Furthermore, 2,3-DPG significantly alleviates oxidative stress and mitochondrial damage induced by oxygen-glucose deprivation/reperfusion (OGD/R). The administration of 2,3-DPG in rats subjected to HIBD resulted in a marked reduction in brain edema and infarct volume, achieved through the suppression of neuronal apoptosis and neuroinflammation. Using RNA-seq analysis, we validated that 2,3-DPG offers protection against neuronal apoptosis under HI conditions by modulating the p38 MAPK pathway. These insights indicated that 2,3-DPG might act as a promising novel therapeutic candidate for HIE.

Ischaemic Colitis from an Unusual Cause: Oral Contraceptives.

Ischaemic colitis is due to insufficiency of intestinal blood flow and is responsible for half of the cases of gastrointestinal ischaemia.Oral contraceptives have an increased odd of 1.05 predisposing development of ischaemic colitis.Symptoms typically resolve with removal of the oral contraceptive.

Investigation of the Physiological and Histopathological Effects of Omega Acids (3, 6, 9) and Stearic Acid on Rats in Ischemia Reperfusion

Ischemia causes reversible or irreversible cell or tissue damage due to insufficient blood flow to the organ or tissue. In this study, our aim is to investigate the protective effect of omega 3, 6 9 and stearic acid application before ischemia reperfusion injury in the leg muscles. For this purpose, 70 female albino rats were divided into 10 groups. The study continued at the same dose for 14 days. In addition, these fatty acids were given to other groups without ischemia-reperfusion. After the application different faty acid, blood biochemical parameters of different fatty acids, oxidative stress parameters and histopathology of tissues (liver, kidney, muscle) were examined in rats. As a result, it was observed that omega 9 fatty acid has better protective properties compared to other omega fatty acids and stearic acid in terms of histopathological properties and oxidative stress index. Additionally, other fatty acids and stearic acid provided some degree of protection against the deleterious effects of ischemia-reperfusion

High Blood Pressure, Hyperlipidemia, Type2 Diabetes with Prior History of Arterial Fibrilation Caused Stroke

The stroke cases are on rise, to know its causes, symptoms & treatment patients have to be studied in detail and get the appropriate result. Stroke is a serious medical condition that can sometimes be deadly. Stroke cases are emerging at a startling rate at the moment. People with specific medical problems are more susceptible to stroke, even though it may afflict anybody. A stroke or brain stroke can be fatal and result from inadequate blood supply to a portion of the brain, according to the Cleveland Clinic. The most common causes of this are cerebral haemorrhage or arterial obstruction. If insufficient blood flow occurs, oxygen-starved brain cells begin to die. A stroke may happen to anybody, at any age, although certain people are more susceptible than others. Furthermore, beyond the age of 65, the danger rises. Strokes occur commonly in either sex. Strokes are the second largest cause of mortality worldwide. Not only that, but stroke is a leading global cause of disability. The following are a few examples of stroke symptoms Paralysis on one sides peaking difficulties or loss of speech distorted or double vision (diplopia) inability to coordinate light headedness and vomiting stiff neck personality shift agitation or confusion seizure loss of memory headache loss of consciousness the blood clotting disorder atherosclerosis Heart abnormality (ventricular or atrial septal defect) microvascular ischemia elevated blood pressure tumours of the brain (including cancer)Heart abnormality (ventricular or atrial septal defect) microvascular ischemia elevated blood pressure tumours of the brain (including cancer) etc.

Computed Tomography Findings in Acute Stroke Patients in a Tertiary center

Background: Stroke, or "cerebrovascular accident," is a medical disorder in which the brain's cells die due to insufficient blood flow. Successful stroke treatment varies according to the type of stroke, whether an infarct or a bleed, and it can be lethal without brain damage. The study aim was to compare clinical stroke diagnosis with computed tomography (CT) scan findings to determine stroke type (hemorrhagic or Ischemic). Methods: This is a descriptive cross-sectional type of study conducted at the Department of Radiology & Imaging in a diagnostic center at central Nepal from December 2023 to February 2024. A total of 120 patients from the inclusion criteria were taken for the study purpose. Data of clinical diagnosis were compared individually with CT findings. Results: Out of 120 patients, 76 were males and 44 were females and they were in the age range of 40 to >70 years. Clinically 59 patients were suspected to have Inermediate (hemorrhagic) infarct, 44 acute cerebral infarct and 17 Intra cerebral hemorrhage. CT scan of the brain showed 58 acute cerebral infarct, 36 Hemorrhagic infarct, 15 Intra cerebral hemorrhage and 7 Space occupying lesion. Conclusion: The study found that CT should be the first thing to do when a person has a stroke because it's easy, quick, and accurate at figuring out infarct and hemorrhage which decides the treatment at a glance.

#1264 Effects of different vascular anastomoses on the transplanted kidney (Inflammation and fibrosis markers from a molecular biological perspective)

Abstract Background and Aims Ischemia-reperfusion injury (IRI) is an unavoidable occurrence in kidney transplantation, and the inflammatory response associated with IRI significantly influences allogeneic immunity and transplant outcomes. Minimizing cold ischemia time is essential to reduce IRI, and anastomosis to the internal or external iliac artery is the preferred arterial anastomotic approach. The purpose of this study was to investigate the effect of anastomotic placement on renal function and whether mRNA levels are a factor that may predict renal function decline after transplantation. Method This study retrospectively encompassed 65 living kidney transplant procedures conducted from January 2019 to March 2023. The cohort was categorized into two groups using preoperative CT scan assessments of calcification: the internal iliac artery anastomosis group (consisting of 31 patients) with calcification rates below 10%, and the external iliac artery anastomosis group (comprising 34 patients) with calcification rates exceeding 10%. We conducted a comprehensive comparison of preoperative, intraoperative, and postoperative parameters for both groups. Furthermore, logistic regression analysis was employed to explore the factors influencing renal function. Given the absence of well-defined criteria for assessing renal function post-transplantation, we established a criterion based on the recipient's estimated glomerular filtration rate (eGFR) at discharge, relative to the preoperative donor eGFR. Patients were categorized into two groups, with divisions falling above and below the midpoint of this criterion, and subjected to comparative analysis. In addition, pathology and RNA-seq analysis were performed on protocol kidney biopsies at 3 months and 1-year post-transplant. Results Preoperative and intraoperative parameters displayed no significant differences between the two groups, and postoperative renal function remained consistent. Notably, in the external iliac group, one patient required reoperation due to anastomotic hemorrhages, while in the internal iliac group, one patient needed re-anastomosis to the external iliac bone due to insufficient blood flow post-anastomosis. No instances necessitated treatment for rejection. The logistic regression analysis revealed that a lack of prior experience with hemodialysis significantly influenced eGFR in the favorable outcome group. Moreover, RNA-seq analysis and pathology identified mutations in the immune system and TGFβ pathway associated with IRI. Conclusion Despite no discernible impact on postoperative renal function attributable to variances in anastomotic arteries, the group with external iliac artery anastomosis exhibited diminished activity in the TGFβ pathway and immune system components associated with fibrosis three months post-operation, hinting at a potentially reduced susceptibility to long-term renal damage. In light of these findings, anastomosing to the external iliac artery appears to be a safe option, and when feasible, it may be the preferable choice for anastomosis in kidney transplantation.

Elevated cortical blood flow insufficiency volume as a predictor of adverse outcomes in aneurysmal subarachnoid hemorrhage: a large prospective quantitative computed tomography perfusion study

PurposeEarly hypoperfusion changes exist in patients with aneurysmal subarachnoid hemorrhage (aSAH). We aimed to investigate a readily obtainable quantitative computed tomography perfusion (CTP) parameter that could assist in quickly identifying patients at risk of delayed cerebral ischemia (DCI) and poor 90-day functional outcomes on admission. MethodsWe prospectively collected data between 2021.04 and 2022.12. Preoperative CTP data were post-processed using RAPID software. The cortical blood flow insufficiency (CBFI) was defined as Time-to-maximum > 4.0 s. Patients were categorized into four groups according to CBFI volume distribution. To minimize differences among the groups, we employed stabilized inverse probability of treatment weighting (sIPTW). The primary outcome was DCI and poor 90-day functional outcomes (modified Rankin Scale, 3–6) was the secondary outcome. Multivariable Cox or Logistic analysis were performed to estimate the association between CBFI volume and the study outcomes, both before and after sIPTW. ResultsAt baseline, the mean (SD) age of the 493 participants was 55.0 (11.8) years, and 299 (60.6%) were female. One hundred and seven participants with DCI and eighty-six participants with poor 90-day functional outcomes were identified. After sIPTW, CBFI volume demonstrated a significant association with DCI (Cox regression: Group 4 versus Group 1, HR 3.69, 95% CI 1.84–7.01) and poor 90-day functional outcomes (Logistic regression: Group 4 versus Group 1, OR 4.61, 95% CI 2.01–12.50). ConclusionIn this study, an elevated preoperative CBFI volume was associated with adverse outcomes in aSAH patients. More well-designed studies are needed to confirm this association.

Arginine-NO metabolites are associated with morbidity in single ventricle infants undergoing stage 2 palliation.

Infants with single ventricle heart disease (SVHD) suffer morbidity from insufficient pulmonary blood flow, which may be related to impaired arginine metabolism. No prior study has reported quantitative mapping of arginine metabolites to evaluate the relationship between circulating metabolite levels and outcomes. Prospective cohort study of 75 SVHD cases peri-Stage 2 and 50 healthy controls. We targeted pre- and post-op absolute serum quantification of 9 key members of the arginine metabolism pathway by tandem mass spectrometry. Primary outcomes were length of stay (LOS) and post-Stage 2 hypoxemia. Pre-op cases showed alteration in 6 metabolites including decreased arginine and increased asymmetric dimethyl arginine (ADMA) levels compared to controls. Post-op cases demonstrated decreased arginine and citrulline levels persisting through 48 h. Adjusting for clinical variables, lower pre-op and 2 h post-op concentrations of multiple metabolites, including arginine and citrulline, were associated with longer post-op LOS (p < 0.01). Increased ADMA at 24 h was associated with greater post-op hypoxemia burden (p < 0.05). Arginine metabolism is impaired in interstage SVHD infants and is further deranged following Stage 2 palliation. Patients with greater metabolite alterations experience greater post-op morbidity. Decreased arginine metabolism may be an important driver of pathology in SVHD. Interstage infants with SVHD have significantly altered arginine-nitric oxide metabolism compared to healthy children with deficiency of multiple pathway intermediates persisting through 48 h post-Stage 2 palliation. After controlling for clinical covariates and classic catheterization-derived predictors of Stage 2 readiness, both lower pre-operation and lower post-operation circulating metabolite levels were associated with longer post-Stage 2 LOS while increased post-Stage 2 ADMA concentration was associated with greater post-op hypoxemia. Arginine metabolism mapping offers potential for development using personalized medicine strategies as a biomarker of Stage 2 readiness and therapeutic target to improve pulmonary vascular health in infants with SVHD.

Diabetic Foot Ulcer Detection: Combining Deep Learning Models for Improved Localization

Diabetes mellitus (DM) can cause chronic foot issues and severe infections, including Diabetic Foot Ulcers (DFUs) that heal slowly due to insufficient blood flow. A recurrence of these ulcers can lead to 84% of lower limb amputations and even cause death. High-risk diabetes patients require expensive medications, regular check-ups, and proper personal hygiene to prevent DFUs, which affect 15–25% of diabetics. Accurate diagnosis, appropriate care, and prompt response can prevent amputations and fatalities through early and reliable DFU detection from image analysis. We propose a comprehensive deep learning-based system for detecting DFUs from patients’ feet images by reliably localizing ulcer points. Our method utilizes innovative model ensemble techniques—non-maximum suppression (NMS), Soft-NMS, and weighted bounding box fusion (WBF)—to combine predictions from state-of-the-art object detection models. The performances of diverse cutting-edge model architectures used in this study complement each other, leading to more generalized and improved results when combined in an ensemble. Our WBF-based approach combining YOLOv8m and FRCNN-ResNet101 achieves a mean average precision (mAP) score of 86.4% at the IoU threshold of 0.5 on the DFUC2020 dataset, significantly outperforming the former benchmark by 12.4%. We also perform external validation on the IEEE DataPort Diabetic Foot dataset which has demonstrated robust and reliable model performance on the qualitative analysis. In conclusion, our study effectively developed an innovative diabetic foot ulcer (DFU) detection system using an ensemble model of deep neural networks (DNNs). This AI-driven tool serves as an initial screening aid for medical professionals, augmenting the diagnostic process by enhancing sensitivity to potential DFU cases. While recognizing the presence of false positives, our research contributes to improving patient care through the integration of human medical expertise with AI-based solutions in DFU management.

Effects of schisandrin B on hypoxia-related cognitive function and protein expression in vascular dementia rats

ABSTRACT Vascular dementia (VD) a heterogenous group of brain disorders in which cognitive impairment is attributable to vascular risk factors and cerebrovascular disease. A common phenomenon in VD is a dysfunctional cerebral regulatory mechanism associated with insufficient cerebral blood flow, ischemia and hypoxia. Under hypoxic conditions oxygen supply to the brain results in neuronal death leading to neurodegenerative diseases including Alzheimer’s (AD) and VD. In conditions of hypoxia and low oxygen perfusion, expression of hypoxia-inducible factor 1 alpha (HIF-1α) increases under conditions of low oxygen and low perfusion associated with upregulation of expression of hypoxia-upregulated mitochondrial movement regulator (HUMMR), which promotes anterograde mitochondrial transport by binding with trafficking protein kinesin 2 (TRAK2). Schisandrin B (Sch B) an active component derived from Chinese herb Wuweizi prevented β-amyloid protein induced morphological alterations and cell death using a SH-SY5Y neuronal cells considered an AD model. It was thus of interest to determine whether Sch B might also alleviate VD using a rat bilateral common carotid artery occlusion (BCAO) dementia model. The aim of this study was to examine the effects of Sch B in BCAO on cognitive functions such as Morris water maze test and underlying mechanisms involving expression of HIF-1α, TRAK2, and HUMMR levels. The results showed that Sch B improved learning and memory function of rats with VD and exerted a protective effect on the hippocampus by inhibition of protein expression of HIF-1α, TRAK2, and HUMMR factors. Evidence indicates that Sch B may be considered as an alternative in VD treatment.

Evaluation of models of sequestration flow in coronary arteries—Physiology versus anatomy?

Background:Myocardial ischaemia results from insufficient coronary blood flow. Computed virtual fractional flow reserve (vFFR) allows quantification of proportional flow loss without the need for invasive pressure-wire testing. In the current study, we describe a novel, conductivity model of side branch flow, referred to as ‘leak’. This leak model is a function of taper and local pressure, the latter of which may change radically when focal disease is present. This builds upon previous techniques, which either ignore side branch flow, or rely purely on anatomical factors. This study aimed to describe a new, conductivity model of side branch flow and compare this with established anatomical models. Methods and results:The novel technique was used to quantify vFFR, distal absolute flow (Qd) and microvascular resistance (CMVR) in 325 idealised 1D models of coronary arteries, modelled from invasive clinical data. Outputs were compared to an established anatomical model of flow. The conductivity model correlated and agreed with the reference model for vFFR (r = 0.895, p < 0.0001; ＋0.02, 95% CI 0.00 to ＋ 0.22), Qd (r = 0.959, p < 0.0001; −5.2 mL/min, 95% CI −52.2 to ＋13.0) and CMVR (r = 0.624, p < 0.0001; ＋50 Woods Units, 95% CI −325 to ＋2549). Conclusion:Agreement between the two techniques was closest for vFFR, with greater proportional differences seen for Qd and CMVR. The conductivity function assumes vessel taper was optimised for the healthy state and that CMVR was not affected by local disease. The latter may be addressed with further refinement of the technique or inferred from complementary image data. The conductivity technique may represent a refinement of current techniques for modelling coronary side-branch flow. Further work is needed to validate the technique against invasive clinical data.

H2S preconditioning induces long-lived perturbations in O2 metabolism

Hydrogen sulfide exposure in moderate doses can induce profound but reversible hypometabolism in mammals. At a cellular level, H2S inhibits the electron transport chain (ETC), augments aerobic glycolysis, and glutamine-dependent carbon utilization via reductive carboxylation; however, the durability of these changes is unknown. We report that despite its volatility, H2S preconditioning increases P50(O2), the O2 pressure for half-maximal cellular respiration, and has pleiotropic effects on oxidative metabolism that persist up to 24 to 48 h later. Notably, cyanide, another complex IV inhibitor, does not induce this type of metabolic memory. Sulfide-mediated prolonged fractional inhibition of complex IV by H2S is modulated by sulfide quinone oxidoreductase, which commits sulfide to oxidative catabolism. Since induced hypometabolism can be beneficial in disease settings that involve insufficient or interrupted blood flow, our study has important implications for attenuating reperfusion-induced ischemic injury and/or prolonging the shelf life of biologics like platelets.

Curcumin alleviates myocardial inflammation, apoptosis, and oxidative stress induced by acute pulmonary embolism by regulating microRNA-145-5P/insulin receptor substrate 1 axis.

The treatment of patients with acute pulmonary embolism (APE) is extremely challenging due to the complex clinical presentation and prognosis of APE related to the patient's hemodynamic status and insufficient arterial blood flow and right ventricular overload. Protective efficacy against cardiovascular diseases of curcumin, a common natural polyphenolic compound, which has antithrombotic properties and reduces platelet accumulation in the circulation by inhibiting thromboxane synthesis has been demonstrated. However, the direct effect of curcumin on APE has rarely been studied. Therefore, the present study aimed to investigate the therapeutic potential of curcumin in APE and associated myocardial injury to provide new insights into curcumin as a promising competitive new target for the treatment of APE. A suspension of 12 mg/kg microspheres was injected intravenously into rats. An APE rat model was built. Before modeling, intragastric 100 mg/kg curcumin was given, and/or lentiviral plasmid vector targeting microRNA-145-5p or insulin receptor substrate 1 (IRS1) was injected. Pulmonary artery pressure was measured to assess right ventricular systolic pressure (RVSP). Hematoxylin and eosin (H&E) staining was performed on liver tissues and myocardial tissues of APE rats. TUNEL (terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling) staining and immunohistochemical (IHC) staining were conducted to measure apoptosis and CyPA-CD147 expression in the myocardium, respectively. Inflammatory indices interleukin-1beta (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) were measured by ELISA in cardiac tissues. RT-qPCR and Western blot were performed to determine the expression levels of related genes. In addition, by dual luciferase reporter assay and RIP assay, the relationship between microRNA-145-5p and insulin receptor substrate 1 (IRS1) was confirmed. In results: curcumin improved APE-induced myocardial injury, reduced myocardial tissue edema, and thrombus volume. It attenuated APE-induced myocardial inflammation and apoptosis, as well as reduced lung injury and pulmonary artery pressure. Curcumin promoted microRNA-145-5p expression in APE rat myocardium. MicroRNA-145-5p overexpression protected against APE-induced myocardial injury, and microRNA-145-5p silencing abolished the beneficial effects of curcumin in APE-induced myocardial injury. IRS1 was targeted by microRNA-145-5p. IRS1 silencing attenuated APE-induced myocardial injury, and enhanced therapeutic effect of curcumin on myocardial injury in APE rats. In conclusion, curcumin alleviates myocardial inflammation, apoptosis, and oxidative stress induced by APE by regulating microRNA-145-5p/IRS1 axis.

Prevalence of Neonatal Hypoxia in District Buner, Pakistan

Background: Neonatal hypoxia, or hypoxic ischemic encephalopathy (HIE), is a significant cause of neonatal morbidity and mortality, especially in developing countries. The condition arises from insufficient oxygen or blood flow to the neonate's brain, leading to various degrees of neurological impairment. This study aims to shed light on the prevalence and characteristics of neonatal hypoxia in District Buner, Khyber Pakhtunkhwa, Pakistan, a region where limited research has been conducted on this critical issue. Objective: The primary objective of this study was to determine the prevalence of neonatal hypoxia in District Buner and to analyse the distribution of its severity across different tehsils within the district. Methods: This retrospective study was conducted from August 2021 to August 2022. Data were collected from several government and private hospitals, including DHQ Daggar, Buner Medical Complex, and Hamdard Medical Center. A total of 753 neonatal hypoxia cases were identified and classified into three categories based on severity: mild (HIE I), moderate (HIE II), and severe (HIE III). The classification was based on Apgar scores and clinical symptoms. The data were statistically analysed using Microsoft Excel 2016 and SPSS software version 25. Results: Out of the 753 neonatal hypoxia cases, 299 (39.7%) were classified as HIE I, 276 (36.6%) as HIE II, and 132 (17.5%) as HIE III. There were 46 fatalities (6.1%) reported. The study also revealed a gender disparity, with males (402 cases, 53.4%) more frequently affected than females (351 cases, 46.6%). The highest incidence of neonatal hypoxia was observed in Tehsil Daggar (25.9%), while Tehsil Khudokhail reported the lowest (6.2%). Conclusion: The study highlights a significant prevalence of neonatal hypoxia in District Buner, with milder forms of HIE being more common. The findings underscore the need for improved obstetric and neonatal care, especially in areas with higher prevalence, to reduce neonatal morbidity and mortality associated with HIE.

5-Methoxytryptophan Alleviates Dextran Sulfate Sodium-Induced Colitis by Inhibiting the Intestinal Epithelial Damage and Inflammatory Response.

Colitis is a refractory intestinal inflammatory disease significantly affecting the quality of a patient's life and increasing the risk of exacerbation. The primary factors leading to colitis encompass infections, insufficient blood flow, and the buildup of collagen as well as white blood cells. Among various available therapeutics, 5-methoxytryptophan (5-MTP) has emerged as one of the protectants by inhibiting inflammatory damage. Nonetheless, there is no report on the role of 5-MTP in the treatment of colitis. To verify the anti-inflammatory effect of 5-MTP in vivo, we first constructed mouse model with dextran sulfate sodium-induced colitis. Furthermore, the macrophage infiltration and release of inflammatory factors through western blot (WB) and hematoxylin-eosin staining analyses were examined. Intestinal epithelial cell tight junction damage and apoptosis were investigated by WB analysis, immunofluorescence, and terminal deoxynucleotidyl transferase dUTP nick end labeling staining. Finally, we examined the generation of cellular inflammation and analyzed the influence of 5-MTP on M1 polarization at the cellular level. This study initially confirmed that 5-MTP possessed an excellent therapeutic effect on colitis. 5-MTP inhibits macrophage infiltration and the generation of inflammatory factors. In addition to its effects on immune cells, 5-MTP significantly inhibits intestinal epithelial cell tight junction damage and apoptosis in vivo. Moreover, it inhibits inflammation and M1 polarization response in vitro. 5-MTP counteracts excessive inflammation, thereby preventing intestinal epithelial tight junction damage. In addition, inhibition of apoptosis suggests that 5-MTP may be a potential therapeutic agent for colitis.

Indocyanine green is an integral part of breast reconstructive surgery using perforator flaps

The use of allotransplants for breast reconstruction in surgical stage of the the breast cancer treatment requires tissue perfusion control. The aim of the study was to analyze the effectiveness of using indocyanine green as a drug for determining the perfusion of perforant flaps in breast reconstructive surgery. A retrospective series of observations of 27 breast reconstructions using autologous transplants is presented: 19 reconstructions with DIEP-flap, 2 with SIEA-flap, 5 with TD-flap; 1 with thoracoepigastric flap. Intraoperative fluorescence angiography was performed using a Stryker device (5900 Optical Court, USA). The intensity of the flap fluorescence was recorded after intravenous bolus injection of 7.5 mg indocyanine green. The optimal time interval from the moment of drug administration to indicative visualization of flap perfusion was 55-60 seconds. In all patients, the area of insufficient blood flow was excised within intensively blood-supplied tissues, according to mapping data with the indocyanine green. With free transplant of flaps postoperative complications during follow-up were recorded in 1 (4.8%) case (marginal necrosis), which is associated with insufficient compression of auxiliary vessels (violation of the dominant vessel contrast technique). With non-free transplant of flaps no complications were detected in the postoperative period. Indocyanine green allows to prevent necrotic changes and reduce the rehabilitation period. The optimal time for the indicative visualization of flap perfusion was 55-60 seconds. The use of indocyanine green in free transplant of flaps ensured a postoperative period without complications in 20 (95.2%) cases, in non-free flap transplantation - in 6 (100%) cases.