Restoration Of Blood Flow Research Articles

Core-Shell Droplet-Based Angiogenic Patches for the Treatment of Ischemic Diseases: Ultrafast Processability, Physical Tunability, and Controlled Delivery of an Angiogenic Cocktail.

The patch-based delivery system has been a promising therapeutic approach for treating various vascular diseases. However, conventional methods face several challenges, including labor-intensive and time-consuming processes associated with patch fabrication or factor incorporation, inadequate physical properties, and uncontrolled release of factors. These limitations restrict the potential applications in clinical settings. To overcome these issues, we propose a novel core-shell-shaped droplet patch system called an angiogenic patch (AP). Our system offers several distinct advantages over conventional patches. It enables a rapid and straightforward fabrication process utilizing only two biodegradable ingredients [alginate and ε-poly(l-lysine)], ensuring minimal toxicity. Moreover, the AP exhibits excellent physical integrity to match and withstand physiological mechanics and allows for customizable patch dimensions tailored to individual patients' pathological conditions. Notably, the AP enables facile loading of angiogenic cytokines during patch fabrication, allowing sustained release at a controlled rate through tunable network cross-linking. Subsequently, the AP, delivering a precisely formulated cocktail of angiogenic cytokines (VEGF, bFGF, EGF, and IGF), demonstrated significant effects on endothelial cell functions (migration and tubule formation) and survival under pathological conditions simulating ischemic injury. Likewise, in in vivo experiments using a mouse model of hindlimb ischemia, the AP encapsulating the angiogenic cocktail effectively restored blood flow following an ischemic insult, promoting muscle regeneration and preventing limb loss. With its simplicity and rapid processability, user-friendly applicability, physical tunability, and the ability to efficiently load and control the delivery of angiogenic factors, the AP holds great promise as a therapeutic means for treating patients with ischemic diseases.

Neuroprotective Effects of Melittin Against Cerebral Ischemia and Inflammatory Injury via Upregulation of MCPIP1 to Suppress NF-κB Activation In Vivo and In Vitro

Melittin, a principal constituent of honeybee venom, exhibits diverse biological effects, encompassing anti-inflammatory capabilities and neuroprotective actions against an array of neurological diseases. In this study, we probed the prospective protective influence of melittin on cerebral ischemia, focusing on its anti-inflammatory activity. Mechanistically, we explored whether monocyte chemotactic protein-induced protein 1 (MCPIP1, also known as ZC3H12A), a recently identified zinc-finger protein, played a role in melittin-mediated anti-inflammation and neuroprotection. Male C57/BL6 mice were subjected to distal middle cerebral artery occlusion to create a focal cerebral cortical ischemia model, with melittin administered intraperitoneally. We evaluated motor functions, brain infarct volume, cerebral blood flow, and inflammatory marker levels within brain tissue, employing quantitative real-time polymerase chain reaction, enzyme-linked immunosorbent assays, and western blotting. In vitro, an immortalized BV-2 microglia culture was stimulated with lipopolysaccharide (LPS) to establish an inflammatory cell model. Post-melittin exposure, cell viability, and cytokine expression were examined. MCPIP1 was silenced using siRNA in LPS-induced BV-2 cells, with the ensuing nuclear translocation of nuclear factor-κB assessed through cellular immunofluorescence. In vivo, melittin enhanced motor functions, diminished infarction, fostered blood flow restoration in ischemic brain regions, and markedly inhibited the expression of inflammatory cytokines (interleukin-1β, interleukin-6, tumor necrosis factor-α, and nuclear factor-κB). In vitro, melittin augmented MCPIP1 expression in LPS-induced BV-2 cells and ameliorated inflammation-induced cell death. The neuroprotective effect conferred by melittin was attenuated upon MCPIP1 knockdown. Our findings establish that melittin-induced tolerance to ischemic injury is intrinsically linked with its anti-inflammatory capacity. Moreover, MCPIP1 is, at the very least, partially implicated in this process.

EAAT3 impedes oligodendrocyte remyelination in chronic cerebral hypoperfusion-induced white matter injury.

Chronic cerebral hypoperfusion-induced demyelination causes progressive white matter injury, although the pathogenic pathways are unknown. The Single Cell Portal and PanglaoDB databases were used to analyze single-cell RNA sequencing experiments to determine the pattern of EAAT3 expression in CNS cells. Immunofluorescence (IF) was used to detect EAAT3 expression in oligodendrocytes and oligodendrocyte progenitor cells (OPCs). EAAT3 levels in mouse brains were measured using a western blot at various phases of development, as well as in traumatic brain injury (TBI) and intracerebral hemorrhage (ICH) mouse models. The mouse bilateral carotid artery stenosis (BCAS) model was used to create white matter injury. IF, Luxol Fast Blue staining, and electron microscopy were used to investigate the effect of remyelination. 5-Ethynyl-2-Deoxy Uridine staining, transwell chamber assays, and IF were used to examine the effects of OPCs' proliferation, migration, and differentiation in vivo and in vitro. The novel object recognition test, the Y-maze test, the rotarod test, and the grid walking test were used to examine the impact of behavioral modifications. A considerable amount of EAAT3 was expressed in OPCs and mature oligodendrocytes, according to single-cell RNA sequencing data. During multiple critical phases of mouse brain development, there were no substantial changes in EAAT3 levels in the hippocampus, cerebral cortex, or white matter. Furthermore, neither the TBI nor ICH models significantly affected the levels of EAAT3 in the aforementioned brain areas. The chronic white matter injury caused by BCAS, on the other hand, resulted in a strikingly high level of EAAT3 expression in the oligodendroglia and white matter. Correspondingly, blocking EAAT3 assisted in the recovery of cognitive and motor impairment as well as the restoration of cerebral blood flow following BCAS. Furthermore, EAAT3 suppression was connected to improved OPCs' survival and proliferation in vivo as well as faster OPCs' proliferation, migration, and differentiation in vitro. Furthermore, this study revealed that the mTOR pathway is implicated in EAAT3-mediated remyelination. Our findings provide the first evidence that abnormally high levels of oligodendroglial EAAT3 in chronic cerebral hypoperfusion impair OPCs' pro-remyelination actions, hence impeding white matter repair and functional recovery. EAAT3 inhibitors could be useful in the treatment of ischemia demyelination.

Endovascular Treatment of Subclavian Artery Occlusion by Surgical Exposure of the Proximal Brachial Artery at the Side of an Arteriovenous Fistula.

A 76-year-old man undergoing hemodialysis complained of pain and discoloration of his right finger. The hemodialysis arteriovenous fistula was in the right upper extremity. Ultrasonography showed right subclavian artery occlusion. The lesion could not be approached from the lower extremity and olecranon artery. Thus, we performed the procedure after exposing the proximal brachial artery. We were able to recanalize the subclavian artery and restore blood flow to the right upper extremity. When the lesion is on the side of the arteriovenous fistula and approaching from the lower extremity is difficult, exposure of the proximal brachial artery can be considered.

The Use of the Pulse Oximeter in Limb Ischemia: The Pulse Study

Purpose: Does a non-invasive pulse oximeter probe accurately indicate limb ischemia with inflation of a tourniquet? How are the pulse waveform, perfusion index and oxygen saturations affected? Does pulse oximetry return to normal with restoration of blood flow? Are the findings similar, regardless of which probe is used? Methods: Single Centre, pilot, proof of concept study. Each volunteer staff member had two probes applied to both lower limbs and then to both upper limbs. One limb had a tourniquet applied (experimental limb). The pulse oximeter trace, perfusion index and oxygen saturations were recorded before tourniquet inflation (time point 0), at inflation (time point 1), just prior to deflation (time point 2) and after deflation when the waveform returned to a biphasic appearance (time point 3). Results: Changes in both pulse oximeter waveforms occurred within 45 seconds of tourniquet inflation, with flattening of the biphasic trace followed by complete loss of amplitude, which normalized on release of the tourniquet. Perfusion index values for the experimental arms and legs were statistically significantly smaller than the control sides during tourniquet inflation and exceeded baseline on deflation, due to reperfusion. Oxygen saturations were unreliable and did not reflect tourniquet inflation. Conclusion: Pulse Oximeter waveform and perfusion index provide a noninvasive, sensitive, responsive, available, repeatable, objective measure of vascular supply in the limbs in healthy volunteers, although oxygen saturation is not a reliable indicator of perfusion. Objective assessment using the pulse oximeter could aid clinical judgement in initiating early vascular intervention in limb injury.

Myocardial ischemia – reperfusion injury

Aim. To summarize and broaden the idea about mechanisms of acute coronary insufficiency development and pathophysiological features of myocardial reperfusion injury. Today, in the event of acute coronary syndrome, according to the latest recommendations for myocardial revascularization, percutaneous coronary intervention should be performed to determine the anatomy of coronary artery lesions and further percutaneous therapy. But in some patients, after blood flow restoration, reperfusion injury occurs, which is primarily related to the duration of ischemia, infarct size, and the myocardial resistance to ischemia. Treatment of myocardial infarction, like any treatment method, has evolved. In the 60s of the previous century, it included morphine, oxygen, warfarin and bed rest for 4–6 weeks. Then, during the 70s, it consisted of morphine, oxygen, lidocaine, warfarin, bed rest for 2–3 weeks and possibly coronary angiography for the further bypass surgery. The late 1970s saw the rapid progress in thrombolysis, first intravenous and then intracoronary. And starting in the early 1980s, since G. Hartzler performed the first balloon angioplasty for acute coronary artery occlusion, the stage of mechanical myocardial reperfusion has come. At the same time, knowledge about the pathophysiology of acute coronary ischemia was deepened. The World Health Organization developed ECG criteria for acute myocardial infarction using population-based studies in the 1950s–1970s, and additional four normative European regulations since then were issued defining concepts, key points of diagnosis and possible complications of myocardial infarction. Conclusions. The development of myocardial ischemic-reperfusion injury is a staged process that has a complex pathogenesis, its own clinical manifestations, and an association with more negative long-term outcomes of myocardial infarction treatment. Its main components are myocardial swelling involving cardiomyocytes, endotheliocytes, and the interstitial space; downregulation of cytoskeleton and disruption of sarcolemma integrity; increased vascular wall permeability; spasm of arterioles; intravascular accumulation of platelets and leukocytes, and the resultant the most severe form of myocardial damage is intramyocardial hemorrhage. Clinically, this is manifested by the no-reflow phenomenon following percutaneous coronary intervention.

Amentoflavone attenuates oxidative stress and neuroinflammation induced by cerebral ischemia/reperfusion in rats by targeting HMGB1-mediated TLR4/NF-κB signaling pathway

Surveys indicated that stroke classified among the leading cause of death as well as combined death and disability worldwide resulting in a great loss for the global economy. The present study aims to evaluate the neuroprotective potential of the biflavonoid amentoflavone (AMNT) in alleviating cerebral ischemia/reperfusion (IR) injury in rats, and to elucidate the possible underlying mechanism of an experimental condition with similar circumstances to stroke. Cerebral ischemia was achieved through left common carotid artery occlusion for 60 min, followed by blood flow restoration. Sham-operated control rats subjected to the same surgical process except for brain IR. Rats were orally administered AMNT/ or vehicle for three days’ prior surgical operation, and for another three days after left brain IR. Rats of all groups were assessed for neurological deficits 24 h following brain IR. Each group was divided into two subgroups one for the rotarod testing and biochemical assessment while the other subgroup to perform the activity cage testing, histopathological study, immunohistochemistry, and gene expression analysis. AMNT enhanced brain levels of GSH and CAT activities, suppressed neuroinflammation via reducing the inflammatory cytokines in the serum, and enhanced brain contents of TBK1 and IFNβ. AMNT downregulated TLR4-/NF-κB signaling pathway as a result of the HMGB1 suppression. Moreover, AMNT blocked apoptotic cell death by suppressing the NF-κB signaling pathway and reducing the activation of caspase-3. These findings revealed that AMNT attenuates I/R–induced cerebral injury possibly by regulating the HMGB1-mediated TLR4/NF-kB pathway. Thus, AMNT could provide potential preventive and therapeutic option for cerebral stroke.

Deep learning‐based surrogate modeling of coronary in‐stent restenosis

AbstractCoronary artery disease (CAD) is one of the largest causes of death worldwide. Percutaneous coronary intervention (PCI) is a minimally invasive procedure to restore blood flow in blocked coronary arteries. However, PCI carries risks such as in‐stent restenosis and thrombosis. Drug‐eluting stents were developed to counteract the restenosis observed after stent implantation. An effective in silico model that can accurately predict the restenosis procedure is of great importance for the cardiology. This study aims to develop a deep learning‐based surrogate model for in‐stent restenosis incorporating anti‐inflammatory drugs embedded in the drug‐eluting stents. The model includes a detailed multiphysics approach based on partial differential equations (PDEs) to capture platelet aggregation, growth‐factor release, cellular motility and drug deposition.

Selective ROCK Inhibitor Enhances Blood Flow Recovery after Hindlimb Ischemia.

The impairment in microvascular network formation could delay the restoration of blood flow after acute limb ischemia. A high-content screen of a GSK-published kinase inhibitor library identified a set of ROCK inhibitor hits enhancing endothelial network formation. Subsequent kinase activity profiling against a panel of 224 protein kinases showed that two indazole-based ROCK inhibitor hits exhibited high selectivity for ROCK1 and ROCK2 isoforms compared to other ROCK inhibitors. One of the chemical entities, GSK429286, was selected for follow-up studies. We found that GSK429286 was ten times more potent in enhancing endothelial tube formation than Fasudil, a classic ROCK inhibitor. ROCK1 inhibition by RNAi phenocopied the angiogenic phenotype of the GSK429286 compound. Using an organotypic angiogenesis co-culture assay, we showed that GSK429286 formed a dense vascular network with thicker endothelial tubes. Next, mice received either vehicle or GSK429286 (10 mg/kg i.p.) for seven days after hindlimb ischemia induction. As assessed by laser speckle contrast imaging, GSK429286 potentiated blood flow recovery after ischemia induction. At the histological level, we found that GSK429286 significantly increased the size of new microvessels in the regenerating areas of ischemic muscles compared with vehicle-treated ones. Our findings reveal that selective ROCK inhibitors have in vitro pro-angiogenic properties and therapeutic potential to restore blood flow in limb ischemia.

Aortic Endograft Infection: Diagnosis and Management.

Aortic endograft infection (AEI) is a rare but life-threatening complication of endovascular aneurysm repair (EVAR). The clinical features of AEI range from generalized weakness and mild fever to fatal aortic rupture or sepsis. The diagnosis of AEI usually depends on clinical manifestations, laboratory tests, and imaging studies. Management of Aortic Graft Infection Collaboration (MAGIC) criteria are often used to diagnose AEI. Surgical removal of the infected endograft, restoration of aortic blood flow, and antimicrobial therapy are the main components of AEI treatment. After removing an infected endograft, in situ aortic reconstruction is often performed instead of an extra-anatomic bypass. Various biological and prosthetic aortic grafts have been used in aortic reconstruction to avoid reinfection, rupture, or occlusion. Each type of graft has its own merits and disadvantages. In patients with an unacceptably high surgical risk and no evidence of an aortic fistula, conservative treatment can be an alternative. Treatment results are determined by bacterial virulence, patient status, including the presence of an aortic fistula, and hospital factors. Considering the severity of this condition, the best strategy is prevention. When encountering a patient with AEI, current practice emphasizes a multidisciplinary team approach to achieve an optimal outcome.

Revascularization and Left Ventricular Dysfunction for ICD Eligibility.

Common triggers for sudden cardiac death (SCD) are transient ischemia, hemodynamic fluctuations, neurocardiovascular influences, and environmental factors. SCD occurs rapidly when sinus rhythm degenerates into ventricular tachycardia (VT) and/or ventricular fibrillation (VF), followed by asystole. Such progressive worsening of the cardiac rhythm is in most cases observed in the setting of ischemic heart disease and often associated with advanced left ventricular (LV) impairment. Revascularization prevents negative outcomes including SCD and heart failure (HF) due to LV dysfunction (LVD). The implantable cardioverter-defibrillator (ICD) on top of medical therapy is superior to antiarrhythmic drugs for patients with LVD and VT/VF. The beneficial effects of ICD have been demonstrated in primary prevention of SCD as well. However, yet debated is the temporal management for patients with LVD who are eligible to ICD prior to revascularization, either through percutaneous or surgical approach. Restoration of coronary blood flow has a dramatic impact on adverse LV remodeling, while it requires aggressive long-term antiplatelet therapy, which might increase complication for eventual ICD procedure when percutaneous strategy is pursued; on the other hand, when LV and/or multiorgan dysfunction is present and coronary artery bypass grafting is chosen, the overall risk is augmented, mostly in HF patients. The aims of this review are to describe the pathophysiologic benefits of revascularization, the studies addressing percutaneous, surgical or no revascularization and ICD implantation, as well as emerging defibrillation strategies for patients deemed at transient risk of SCD and/or at higher risk for transvenous ICD implantation.

Liver reportalization in extrahepatic portal hypertension

The study involved literature review of history and current state of surgical treatment in extrahepatic portal hypertension in children and adults. The author analyzed Russian and foreign publications on surgical repair of hepatopetal blood flow in extrahepatic portal hypertension. The issue is a high priority in Russia, which is confirmed by the fact that the author found out the pioneer studies of Russian authors, which were published earlier than the works of foreign researchers. It was found that the role of hepatopetal blood flow restoration in extrahepatic portal hypertension in adults had been much less studied than in children. More clinical material is to be gathered to determine the feasibility of such interventions in adults.

Advancements in Myocardial Infarction Management: Exploring Novel Approaches and Strategies.

In the landscape of healthcare, the management of myocardial infarction (MI) stands as a pivotal challenge and a critical juncture where advancements are reshaping the trajectory of patient care. Myocardial infarction, commonly known as a heart attack, remains a foremost contributor to global morbidity and mortality. Conventional management strategies have historically focused on rapid restoration of blood flow through revascularization techniques. However, the last decade has witnessed a profound transformation, with a burgeoning emphasis on precision medicine and innovative interventions. This contextual backdrop sets the stage for a deep dive into the realm of novel diagnostic modalities, spanning high-sensitivity biomarkers, advanced imaging techniques, and data-driven algorithms. These innovations facilitate not only early detection but also the stratification of patients, paving the way for individualized treatment plans. By targeting the underlying mechanisms of myocardial damage, these interventions hold the promise of attenuating the impact of MI and promoting cardiac regeneration. It examines the integration of telemedicine, wearable devices, and remote monitoring platforms, bridging the gap between patients and caregivers while enabling timely interventions. Additionally, the psychosocial aspects of MI recovery are explored, highlighting the integration of psychological support and lifestyle interventions to enhance long-term well-being. By exploring novel diagnostics, innovative therapies, and holistic patient-centered strategies, it underscores the collaborative efforts of medical practitioners, researchers, and technological pioneers in reshaping the trajectory of MI care. As we stand at the intersection of medical advancement and compassionate patient management, embracing these novel approaches promises a future where the impact of myocardial infarction can be mitigated, and lives can be extended and enriched.

Unveiling pro-angiogenesis and drug delivery using dual-bio polymer with bio-ceramic based nanocomposite hydrogels

In regenerative medicine, blood vessel development is of utmost importance as it enables the restoration of blood flow to tissues, and facilitate rapid vascularization in clinical tissue-engineered grafts. Herein, we fabricate the nanocomposite hydrogels from BG (clinophosinaite), alginate, Polyethylene glycol (PEG) and Dexamethasone (DEX) for the dual applications of drug delivery and angiogenesis assay. The hydrogels were fabricated through cross-linking approach and termed as alginate/PEG (A), alginate/PEG/clinophosinaite (AC), and alginate/PEG/clinophosinaite/DEX (ACD) that further subjected to structural characterization, using powder X-ray diffraction, and fourier-transform infrared spectroscopy. Porous nanostructures and sheets were imaged using field emission scanning electron microscopy (FESEM), which aid in nutrient and oxygen transport to support angiogenesis. The nanocomposite hydrogels evidently demonstrated good hemocompatibility and fully hydrophilic (30.20°). By means of liquid displacement technique, the nanocomposite hydrogel achieves 47% of porosity with the compressive strength about 0.04 MPa. In alginate/PEG/clinophosinaite and alginate/PEG/clinophosinaite/DEX systems, water absorption capacity reached 85% in 6 h and maintained 90% retention after 12 h. Further, leachable tests revealed that the hydrogel had not deformed even after 24 h. In vitro drug release studies evidently divulge sustainable delivery of DEX from alginate/PEG/clinophosinaite/DEX hydrogel with superior characteristics for drug release. The angiogenesis assay also evidently revealed that the AC and ACD hydrogels, demonstrated higher angiogenic properties with, promoted blood vessel development.

Rescue treatment with tPA for refractory thromboembolism during stent-assisted coiling of a ruptured intracranial aneurysm: A case report

Thromboembolic complications during stent-assisted coiling of ruptured intracranial aneurysms are major complications that can cause serious neurological deficits. Management strategies include medical thrombolysis, mechanical thrombectomy with suction aspiration or stent retrieval, and rescue stenting. The existing literature suggests that tissue plasminogen activator agents should be used cautiously because of the high risk of severe bleeding at the aneurysm. We present the case of a ruptured anterior communicating artery aneurysm. Acute in-stent thrombosis occurred during the stent-assisted coiling of the aneurysm. Rescue therapy with tirofiban, suction aspiration, and rescue stenting was attempted; however, these methods failed. Finally, tissue plasminogen activator infusion was performed, which successfully dissolved the thrombus and restored blood flow. Follow-up brain computed tomography revealed no increase in hemorrhage volume.

Prophylactic Treatment of Intestinal Ischemia-Reperfusion Injury Reduces Mucosal Damage and Improves Intestinal Absorption.

Intestinal ischemia-reperfusion injury (i-IRI) involves a blood flow interruption in an intestinal segment followed by blood flow restoration. When blood flow is restored, oxidative and inflammatory molecules are distributed throughout the bloodstream, triggering both local and systemic damage. Our goal was to evaluate the potential of three antioxidant and/or anti-inflammatory compounds (curcumin, dexmedetomidine and α-tocopherol) to prevent or reverse local and systemic damage induced by i-IRI. i-IRI was induced by placing a microvascular clip in the superior mesenteric artery of female WAG/RijHsd rats; the clip was removed after 1h and reperfusion was allowed for 4h. Curcumin (200 mg/kg, orally), α-tocopherol (20 mg/kg, i.p.), and dexmedetomidine (5 or 20 µg/kg, s.c.; DEX5 and DEX20, respectively) were administered. Blood and terminal ileum specimens were collected for biochemical and histological determination. Furthermore, D-xylose absorption test was performed to evaluate intestinal absorption; after completing the 1-hour ischemia and 4-hour reperfusion period, 1 mL of aqueous D-xylose solution (0.615 mg/mL) was administered orally, and one hour later, plasma D-xylose levels were quantified. The histological injury degree (HID) measured by the Chiu scale was significantly reduced when the treatments were applied (non-treated rats, 2.6 ± 0.75; curcumin, 1.54 ± 0.8; DEX5, 1.47 ± 0.7; DEX20 1.14 ± 0.5; and α-tocopherol, 1.01 ± 0.6); intestinal absorptive capacity also improved in all cases healthy rats (2.06 ± 0.07 µg/mL; non-treated, 1.18 ± 0.07 µg/mL; curcumin 1.76 ± 0.3 µg/mL; DEX5, 2.29 ± 0.2 µg/mL; DEX20, 2.25 ± 0.26 µg/mL; and α-tocopherol 1.66 ± 0.21 µg/mL). However, it failed to reduce liver enzyme levels. Finally, only dexmedetomidine significantly reduced urea and creatinine levels compared to non-treated animals. All drugs were effective in reducing HID, although α-tocopherol was effective to a greater extent. Only dexmedetomidine reverted intestinal absorption to normal values of healthy animals.

Characterization of cardiovascular and cerebrovascular controls via spectral causality analysis in patients undergoing surgical aortic valve replacement during a three-month follow-up

Objective. Aortic valve stenosis (AVS) induces left ventricular function adaptations and surgical aortic valve replacement (SAVR) restores blood flow profile across aortic valve. Modifications of cardiac hemodynamics induced by AVS and SAVR might alter cardiovascular (CV) and cerebrovascular (CBV) controls. The study aims at characterizing CV and CBV regulations one day before SAVR (PRE), within one week after SAVR (POST), and after a three-month follow-up (POST3) in 73 AVS patients (age: 63.9 ± 12.9 yrs; 48 males, 25 females) from spontaneous fluctuations of heart period (HP), systolic arterial pressure, mean arterial pressure and mean cerebral blood velocity. Approach. CV and CBV regulations were typified via a bivariate autoregressive approach computing traditional frequency domain markers and causal squared coherence (CK 2) from CV and CBV variabilities. Univariate time and frequency domain indexes were calculated as well. Analyses were carried out in frequency bands typical of CV and CBV controls at supine rest and during active standing. A surrogate method was exploited to check uncoupling condition. Main results. We found that: (i) CV regulation is impaired in AVS patients; (ii) CV regulation worsens in POST; (iii) CV regulation recovers in POST3 and CV response to active standing is even better than in PRE; (iv) CBV regulation is preserved in AVS patients; (v) SAVR does not affect CBV control; (vi) parameters of the CBV control in POST3 and PRE are similar. Significance. CK 2 is particularly useful to characterize CV and CBV controls in AVS patients and to monitor of patient’s evolution after SAVR.

Lignin/Puerarin Nanoparticle-Incorporated Hydrogel Improves Angiogenesis through Puerarin-Induced Autophagy Activation.

Puerarin is the main isoflavone extracted from Radix Puerariae lobata (Willd.) and exerts a strong protective effect on endothelial cells. This isoflavone also exerts proven angiogenic effects; however, the potential underlying mechanism has not been fully explored. Here in this work, we aimed to determine the proangiogenesis effect of a puerarin-attached lignin nanoparticle-incorporated hydrogel and explore the underlying mechanism. Puerarin-attached lignin nanoparticles were fabricated and mixed with the GelMA hydrogel. After the hydrogel was characterized, the angiogenic effect was evaluated in a mouse hind-limb ischemia model. To further explore the mechanism of angiogenesis, human endothelial cell line EA.hy926 was exposure to different concentrations of puerarin. Wound healing assays and tube formation assays were used to investigate the effects of puerarin on cell migration and angiogenesis. qPCR and Western blotting were performed to determine the changes in the levels of angiogenesis indicators, autophagy indicators and PPARβ/δ. 3-MA was used to assess the role of autophagy in the puerarin-mediated angiogenesis effect in vivo and in vitro. The hydrogel significantly improved blood flow restoration in mice with hind-limb ischemia. This effect was mainly due to puerarin-mediated increases in the angiogenic capacity of endothelial cells and the promotion of autophagy activation. A potential underlying mechanism might be that puerarin-mediated activation of autophagy could induce an increase in PPARβ/δ expression. The puerarin-attached lignin nanoparticle-incorporated hydrogel effectively alleviated blood perfusion in mice with hind-limb ischemia. Puerarin has a prominent proangiogenic effect. The potential mechanisms might be that puerarin-mediated autophagy activation and increase in PPARβ/δ.

Microsurgical autologous ffbula transfer as an optimal method for closure of extensive bone defects in children with neuroffbromatosis

Introduction Pseudarthrosis and bone defects are the most common consequence of neurofibromatosis type I in children, a rare hereditary disease. Destruction of bone tissue leads to severe deformities and impaired function of the limbs. Disability in such patients may reach 70 %. Surgical treatment of children with this pathology is long, laborious and multi-stage. Traditional orthopaedic methods for managing bone defects are often ineffective. The development of microsurgical methods enables to perform bone transfer of blood-supplied bone autografts.Purpose To prove the effectiveness of using microsurgical autologous transfer of the vascularized fibula for plastic surgery of bone defects in children with neurofibromatosis type I.Materials and methods A retrospective monocenter study included 27 pediatric patients who underwent reconstruction of bone defects with a vascularized fibular autograft from 2011 to 2021. The etiology of the bone defect in all patients was neurofibromatosis type I. A fibula graft was used to reconstruct 8 tibiae and 19 forearms. Bone defects averaged 12 cm. Median follow-up was 60 months.Results The fibula graft survival rate was 100 %. In 5 cases, nonunion of the proximal part of the fibula and the recipient zone was obtained which required iliac crest grafting. The overall rate of good and excellent results was 74 %. The average time to consolidation was 3 months. Discussion According to the literature, the use of autografting of vascularized bone fragments is a ather limited procedure in children with neurofibromatosis type I as it is associated with an increased risk of complications. Due to the restoration of blood flow in the transferred vascularized autograft, it retains its viability and the possibility of bone tissue remodeling.Conclusion Microsurgical autologous transfer of a vascularised fragment of the fibula is an effective and at times indispensable method of bone plasty in long bone defects in children with type 1 neurofibromatosis. Bone defects larger than 5 cm are an indication for free autologous transfer of a vascularized fragment of the fibula. This method, used in combination with traditional orthopedic methods for the treatment of children, allows obtaining good anatomical and functional results.

Combinatorial Nutraceutical Supplement Pill (CNSP) activates naïve adult telomerase positive stem cells in-situ to heal cardiomyopathies

Thirty percent of all deaths worldwide can be attributed to cardiovascular diseases. Myocardial infarction is due to one or more blocked coronary vessels. Following a myocardial infarction, the damaged myocardium is often replaced with non-functional scar tissue, resulting in heart failure. The prognosis of patients with heart failure is poor, with failure rates approaching 50%. Lack of blood flow is a major contributor. Multiple strategies have been developed to restore blood flow to the damaged myocardium. These strategies include pharmacological treatments, reopening the blockage with stents, bypassing the blockage with coronary arterial bypass grafts, and/or forming new blood vessels with stem cells. Since none of these strategies have proved to be permanent fixes, ex vivo activated adult telomerase-positive stem cells (aTPSCs) were examined to restore the damaged myocardium and vasculature of the heart. Individuals with cardiac outputs >25% were treated with ex vivo activated aTPSCs. Following treatment, cardiac output increased from 20-45% for 12+ years in these individuals. These results suggest that ex vivo activated aTPSCs are a viable option for the treatment of individuals with cardiovascular disease. Unfortunately, some individuals with cardiac outputs at or below 10% are too fragile to undergo the ex vivo activated aTPSC procedures. Therefore, a nutraceutical formulation (CNSP) was developed to activate the aTPSCs in-situ for cardiac repair. In an individual with a cardiac output of less than 10%, cardiac output increased by 25% following six months ingestion of CNSP. And increased cardiac output of 10-15% occurred after an additional 12-36+ months of CNSP.