Detoxification and Activating Blood Circulation Decoction Promotes Reendothelialization of Damaged Blood Vessels via VEGF Signaling Pathway Activation by miRNA-126.

The occurrence of in-stent restenosis (ISR) poses a significant challenge for percutaneous coronary intervention (PCI). Thus, the promotion of vascular reendothelialization is essential to inhibit endothelial proliferation. In this study, we clarified the mechanism by which Detoxification and Activating Blood Circulation Decoction (DABCD) promotes vascular reendothelialization to avoid ISR by miRNA-126-mediated modulation of the vascular endothelial growth factor (VEGF) signaling pathway. A rat model of post-PCI restenosis was established by balloon injury. The injured aortic segment was collected 14 and 28 d after model establishment. Our findings indicate that on the 14th and 28th days following balloon injury, DABCD reduced intimal hyperplasia and inflammation and promoted vascular reendothelialization. Additionally, DABCD markedly increased NO expression and significantly decreased ET-1 production in rat serum. DABCD also increased the mRNA level of eNOS and the protein expression of VEGF, p-Akt, and p-ERK1/2 in vascular tissue. Unexpectedly, the expression of miR-126a-5p mRNA was significantly lower in the aortic tissue of balloon-injured rats than in the aortic tissue of control rats, and higher miR-126a-5p levels were observed in the DABCD groups. The results of this study indicated that the vascular reendothelialization effect of DABCD on arterial intimal injury is associated with the inhibition of neointimal formation and the enhancement of vascular endothelial activity. More specifically, the effects of DABCD were mediated, at least in part, through miR-126-mediated VEGF signaling pathway activation.

Considerations on static pressure gradients in closed circulatory systems.

Siphons are devices that transport liquids uphill between two containers. It has been proposed that a siphon principle operates in closed circulatory systems, as best exemplified by the circulation of blood in mammals. This principle is supposed to ensure that no additional work is necessary to pump blood above the level of the heart, and that there is no gravitational static pressure gradient in the column of blood. The first statement is correct, while we demonstrate that, ignoring hydraulic resistance to blood flow, the static pressure gradient is equal to the hydrostatic gradient in a siphon model of blood circulation, although the details of the proof do not depend on the geometry of the circulatory system and the proof can be trivially extended to other models such as a vascular waterfall. This implies that the controversy over the siphon principle has no implications for the description of blood circulation, and that mechanisms such as the "baffle," which some authors have appealed to in order to obtain the expected gradient, are not necessary. In our discussion, we also discuss empirical data that appear to provide additional verification of our results, as well as several everyday occurrences that provide additional support.

Supplementation with cassis polyphenol has no effect on menopausal symptoms in healthy middle-aged women: A randomized, double-blind, parallel-group, placebo-controlled trial.

Hormonal changes during the menopause transition may lead to vasomotor symptoms, including hot flashes (HFs) and neuropsychiatric symptoms such as anxiety and irritability. We hypothesized that the effects of cassis polyphenol (CaP) to improve microcirculation and vasorelaxation may alleviate menopausal symptoms. We performed a randomized, double-blind, parallel-group, placebo-controlled trial involving 59 healthy women (mean [standard deviation] age, 51.3 [4.3] years; body mass index, 20.8 [2.6] kg/m2). Participants experiencing subjective menopausal symptoms consumed CaP tablets (400 mg/d, CaP group) or placebo tablets (placebo group) for 4 weeks. Participants were evaluated using questionnaires at baseline, during the 4-week intervention period, and during a 2-week postinterventional observation period. The primary objective was to evaluate the effects of supplementation with CaP on HFs in healthy Japanese women with menopausal symptoms. Additional assessments included the modified Kupperman menopausal index, World Health Organization-5 Well-Being Index, World Health Organization quality-of-life 26-item index, State-Trait Anxiety Inventory (anxiety and trait components), and Oguri-Shirakawa-Azumi sleep inventory (middle-aged and elderly versions). During the 4-week intervention period, no significant between-group differences were detected in the HF frequency, HF score, sweating frequency, menopausal symptoms, quality of life, anxiety, or sleep. During the 2-week postintervention observational period, the HF score and sweating frequency were significantly decreased in the CaP group compared with the placebo group. These findings suggest that twice daily intake of CaP for 4 weeks does not alleviate menopause symptoms, but the improvement observed in the CaP intake group during the postintervention period warrants confirmation through further large-scale studies.

Nile Tilapia (Oreochromis niloticus) Patched1 Mutations Disrupt Cardiovascular Development and Vascular Integrity through Smoothened Signaling.

Hedgehog (Hh) signaling is crucial in cardiovascular development and maintenance. However, the biological role of Patched1 (Ptch1), an inhibitory receptor of the Hh signaling pathway, remains elusive. In this study, a Ptch1 ortholog was characterized in Nile tilapia (Oreochromis niloticus), and its function was investigated through CRISPR/Cas9 gene knockout. When one-cell embryos were injected with CRISPR/Cas9 targeting ptch1, the mutation efficiency exceeded 70%. During 0-3 days post fertilization (dpf), no significant differences were observed between the ptch1 mutant group and the control group; at 4 dpf (0 day after hatching), about 10% of the larvae showed an angiogenesis defect and absence of blood flow; from 5 dpf, most larvae exhibited an elongated heart, large pericardial cavity, and blood leakage and coagulation, ultimately dying during the 6-8 dpf period due to the lack of blood circulation. Consistently, multiple differentially expressed genes related to angiogenesis, blood coagulation, and heart development were enriched in the ptch1 mutants. Furthermore, Smoothened (Smo) antagonist (cyclopamine) treatment of the ptch1 mutants greatly rescued the cardiovascular disorders. Collectively, our study suggests that Ptch1 is required for cardiovascular development and vascular integrity via Smo signaling, and excessive Hh signaling is detrimental to cardiovascular development.

Treatment of diabetic retinopathy with herbs for tonifying kidney and activating blood circulation: A review of pharmacological studies.

ETHNOPHARMACOLOGICAL RELEVANCE: Diabetic retinopathy (DR) is a prevalent microvascular complication of diabetes. Chinese medicine believes that kidney deficiency and blood stasis are significant pathogenesis of DR. A characteristic therapeutic approach for this pathogenesis is the kidney-tonifying and blood-activating method. By literature retrieval from several databases, we methodically summarized the commonly used kidney-tonifying and blood-activating herbs for treating DR, including Lycii Fructus, Rehmanniane Radix Praeparata, and Corni Fructus with the function of nourishing kidney; Salvia Miltiorrhizae Radix et Rhizoma with the function of enhancing blood circulation; Rehmanniae Radix with the function of nourishing kidney yin; and Astragali Radix with the function of tonifying qi. It has been demonstrated that these Chinese herbs described above, by tonifying the kidney and activating blood circulation, significantly improve the course of DR. AIM OF THE STUDY: Through literature research, to gain a thorough comprehension of the pathogenesis of DR. Simultaneously, through the traditional application analysis, modern pharmacology research and network pharmacology analysis of kidney-tonifying and blood-activating herbs, to review the effectiveness and advantages of kidney-tonifying and blood-activating herbs in treating DR comprehensively. MATERIALS AND METHODS: PubMed, the China National Knowledge Infrastructure (CNKI), and Wanfang Data were used to filter the most popular herbs for tonifying kidney and activating blood in the treatment of DR. The search terms were "diabetic retinopathy" and "tonifying kidney and activating blood". Mostly from 2000 to 2023. Network pharmacology was applied to examine the key active components and forecast the mechanisms of kidney-tonifying and blood-activating herbs in the treatment of DR. RESULTS: Kidney deficiency and blood stasis are the pathogenesis of DR, and the pathogenesis is linked to oxidative stress, inflammation, hypoxia, and hyperglycemia. Scientific data and network pharmacology analysis have demonstrated the benefit of tonifying kidney and activating blood herbs in treating DR through several channels, multiple components, and multiple targets. CONCLUSIONS: This review first presents useful information for subsequent research into the material foundation and pharmacodynamics of herbs for tonifying kidney and activating blood, and offers fresh insights into the treatment of DR.

Endothelial-Specific Reduction in Arf6 Impairs Insulin-Stimulated Vasodilation and Skeletal Muscle Blood Flow Resulting in Systemic Insulin Resistance in Mice.

BACKGROUND: Much of what we know about insulin resistance is based on studies from metabolically active tissues such as the liver, adipose tissue, and skeletal muscle. Emerging evidence suggests that the vascular endothelium plays a crucial role in systemic insulin resistance; however, the underlying mechanisms remain incompletely understood. Arf6 (ADP ribosylation factor 6) is a small GTPase that plays a critical role in endothelial cell function. Here, we tested the hypothesis that the deletion of endothelial Arf6 will result in systemic insulin resistance. METHODS: We used mouse models of constitutive endothelial cell-specific Arf6 deletion (Arf6f/- Tie2Cre+) and tamoxifen-inducible Arf6 knockout (Arf6f/f Cdh5CreER+). Endothelium-dependent vasodilation was assessed using pressure myography. Metabolic function was assessed using a battery of metabolic assessments including glucose and insulin tolerance tests and hyperinsulinemic-euglycemic clamps. We used a fluorescence microsphere-based technique to measure tissue blood flow. Skeletal muscle capillary density was assessed using intravital microscopy. RESULTS: Endothelial Arf6 deletion impaired insulin-stimulated vasodilation in white adipose tissue and skeletal muscle feed arteries. The impairment in vasodilation was primarily due to attenuated insulin-stimulated nitric oxide bioavailability but independent of altered acetylcholine-mediated or sodium nitroprusside-mediated vasodilation. Endothelial cell-specific deletion of Arf6 also resulted in systematic insulin resistance in normal chow-fed mice and glucose intolerance in high-fat diet-fed obese mice. The underlying mechanisms of glucose intolerance were reductions in insulin-stimulated blood flow and glucose uptake in the skeletal muscle and were independent of changes in capillary density or vascular permeability. CONCLUSIONS: Results from this study support the conclusion that endothelial Arf6 signaling is essential for maintaining insulin sensitivity. Reduced expression of endothelial Arf6 impairs insulin-mediated vasodilation and results in systemic insulin resistance. These results have therapeutic implications for diseases that are associated with endothelial cell dysfunction and insulin resistance such as diabetes.

Simulating impaired left ventricular-arterial coupling in aging and disease: a systematic review.

Aortic stenosis, hypertension, and left ventricular hypertrophy often coexist in the elderly, causing a detrimental mismatch in coupling between the heart and vasculature known as ventricular-vascular (VA) coupling. Impaired left VA coupling, a critical aspect of cardiovascular dysfunction in aging and disease, poses significant challenges for optimal cardiovascular performance. This systematic review aims to assess the impact of simulating and studying this coupling through computational models. By conducting a comprehensive analysis of 34 relevant articles obtained from esteemed databases such as Web of Science, Scopus, and PubMed until July 14, 2022, we explore various modeling techniques and simulation approaches employed to unravel the complex mechanisms underlying this impairment. Our review highlights the essential role of computational models in providing detailed insights beyond clinical observations, enabling a deeper understanding of the cardiovascular system. By elucidating the existing models of the heart (3D, 2D, and 0D), cardiac valves, and blood vessels (3D, 1D, and 0D), as well as discussing mechanical boundary conditions, model parameterization and validation, coupling approaches, computer resources and diverse applications, we establish a comprehensive overview of the field. The descriptions as well as the pros and cons on the choices of different dimensionality in heart, valve, and circulation are provided. Crucially, we emphasize the significance of evaluating heart-vessel interaction in pathological conditions and propose future research directions, such as the development of fully coupled personalized multidimensional models, integration of deep learning techniques, and comprehensive assessment of confounding effects on biomarkers.

Small molecule conjugation reduces macrophage uptake and increases in vivo blood circulation of polystyrene nanoparticles.

Nanomedicine often failed clinically to show therapeutic efficacy due to reduced particle circulation and enhanced capture by the reticuloendothelial system (RES), including the liver. Developing novel immunomodulatory surface coating can prevent macrophage capture and increase the particle circulation of the nanomedicine, resulting in higher therapeutic efficiency. Herein, we demonstrate the development of immunomodulatory small molecule (RZA15) with triazole functionality using copper-catalyzed click chemistry to conjugate onto spherical polystyrene nanoparticles using amide coupling reactions, achieving higher blood circulation and lesser macrophage uptake of the nanoconjugates. In this work, we evaluated the effectiveness of RZA15 coating for the enhanced circulation of polystyrene nanoparticles of 100 nm size, which is commonly utilized for various drug delivery applications, and compared with poly(ethylene)glycol (PEG) coatings. Several polystyrene nanoconjugate formulations were analyzed in vitro in normal and macrophage cells for cell viability and cellular uptake studies. In vitro studies demonstrated lesser macrophage uptake of the nanoconjugates following RZA15 coating. Finally, in vivo, blood-circulation, pharmacokinetics, and biodistribution studies were performed in the C57BL/6J mouse model that endorsed the substantial role of RZA15 in preventing liver and spleen capture and results in extended circulation. Coating immunomodulatory small molecules to nanoparticles can severely enhance the potential therapeutic effects of nanomedicine at lower doses.

Exploring Modern Mechanism of Treating Diabetic Retinopathy and Coronary Heart Disease from Perspective of Blood Stasis Under Viewpoint of Treating Different Diseases with the Same Method / 中国实验方剂学杂志

Diabetic retinopathy（DR） and coronary heart disease（CHD） are both major chronic vascular complications that seriously jeopardize the health of the population and often occur together in clinical practice， it is of great clinical value to actively explore the association between the two in the process of disease development and methods of prevention and treatment of modern medicine and traditional Chinese medicine（TCM）. According to TCM， the heart and eyes physiologically communicate with each other by taking Qi， blood and veins as bridges， blood stasis obstructing collaterals is the common TCM etiology of DR and CHD， whose mechanism involves inflammation， oxidative stress and endothelial dysfunction. Promoting blood circulation and removing blood stasis plays an important role in the same treatment for different diseases and prevention and treatment of comorbidities， possibly by inhibiting the expression of interleukin-1β（IL-1β）， endothelin-1（ET-1） and hypoxia inducible factor-1α/vascular endothelial growth factor（HIF-1α/VEGF）， regulating phosphatidylinositol 3-kinases/protein kinase B/mammalian target of rapamycin（PI3K/Akt/mTOR） pathway， initiating adenosine monophosphate（AMP）-activated protein kinase/silent information regulator 1（AMPK/SIRT1） and nuclear transcription factor erythroid 2-related factor 2/heme oxygenase-1（Nrf2/HO-1） signaling pathways， inhibiting Hippo/Yes-associated protein（Hippo/YAP） signaling pathway， inhibiting mitochondrial permeability transition pore and anti-platelet agglutination for treating DR and CHD， which provides a multi-component， multi-pathway and multi-target selection strategies and ideas for the prevention and treatment of DR and CHD by TCM from a biological perspective. Based on this， subsequent studies should focus on constructing clinically relevant comorbidity models， conducting multicenter prospective studies， and fully utilizing artificial intelligence technology to gain a deeper understanding of the relationship between the two diseases， so as to elucidate the mechanism of promoting blood circulation and removing blood stasis in preventing and treating panvascular diseases.

Cardiac output and the pharmacology of general anesthetics: a narrative review

The relationship between cardiac output and anesthetic drugs is important to anesthesiologists, since cardiac output determines the speed with which a drug infused into the bloodstream reaches its target and the intensity of the drug's effect. But rather than focus on how anesthetic drugs affect cardiac output, this narrative review focuses on how changes in cardiac output affect the pharmacokinetics and pharmacodynamics of general anesthetics during the three phases of anesthesia. At induction, an increase in cardiac output shortens both the onset time of propofol for hypnosis and the neuromuscular blocking effect of rapid-acting neuromuscular blockers, favoring the conditions for rapid sequence intubation. During maintenance, changes in cardiac output are followed by opposite changes in the drug plasma concentration of anesthetic drugs. Thus, an increase in cardiac output followed by a decrease in the plasma concentration of the anesthetic could expose the patient to a real risk of intraoperative awakening, which can be avoided by increasing the dose of hypnotic drugs. At emergence, an increase in cardiac output secondary to an increase in pC02 allows for a more rapid recovery from anesthesia. The pC02 can be increased by adding CO2 to the respiratory circuit, lowering the ventilatory rate, or placing the patient on partial rebreathing. Finally, the reversal action of sugammadex for rocuronium-induced neuromuscular block can be shortened by increasing the cardiac output.

La relación entre el gasto cardíaco y los fármacos anestésicos es importante para los anestesiólogos puesto que el gasto cardíaco determina la velocidad con la cual un medicamento que se infunde al torrente sanguíneo llega a su diana y la intensidad del efecto del agente. Pero en lugar de concentrarnos en cómo los fármacos anestésicos afectan el gasto cardíaco, esta revisión narrativa se enfoca en cómo los cambios en el gasto cardíaco afectan la farmacocinética y la farmacodinámica de los agentes anestésicos generales durante las tres fases de la anestesia. En el momento de la inducción, un incremento en el gasto cardíaco acorta tanto el tiempo de inicio del efecto del propofol para la hipnosis como el efecto del bloqueo neuromuscular causado por los bloqueadores neuromusculares de acción rápida, favoreciendo las condiciones para la intubación de secuencia rápida. Durante la fase de mantenimiento, los cambios en el gasto cardíaco vienen seguidos de cambios opuestos en la concentración plasmática del medicamento de los agentes anestésicos. Por lo tanto, un aumento del gasto cardíaco, seguido de una reducción en la concentración plasmática del anestésico, podría exponer al paciente a un riesgo real de despertar intraoperatorio, lo cual puede evitarse aumentando la dosis de los fármacos hipnóticos. En la educción, un aumento en el gasto cardíaco secundario al incremento en el pCO2 permite una recuperación más rápida de la anestesia. El pCO2 puede aumentar agregando CO2 al circuito de la respiración, reduciendo la tasa ventilatoria, o colocando al paciente en re-inhalación parcial. Finalmente, la acción de reversión de sugammadex en caso de bloqueo neuromuscular inducido por rocuronio, puede acortarse aumentando el gasto cardíaco.

Active Contraction in the Stable Mechanical Environment of the Tunic of the Ascidian, Halocynthia roretzi, a Polysaccharide-Based Tissue with Blood Circulatory System.

Halocynthia roretzi, a member of Ascidiacea, is covered with its own tunic, which is composed of polysaccharides, such as cellulose Iß and sulfated chitin. H. roretzi has an open-vessel system, whose blood vessels and hemocytes are found in the tunic, so that the mechanical environment of the tunic could be carefully controlled because of its influence on hemocyte behaviors. While active deformation of the tunic and related phenomena have been previously reported, the mechanical environment in the tunic, which directly influences its deformation, has been rarely investigated. Meanwhile, the developments of actuators based on cellulose and chitin have been frequently reported. However, a cellulose-sulfated chitin actuator has not been proposed. In this study, the mechanical environment of the tunic, which has been rarely investigated despite its importance in the active deformation of the tunic, was evaluated using finite element analysis. A finite element model of the tunic, based on its histological characteristics as well as deformation patterns, was developed. The results showed that the shape of the tunic, the pattern of fiber distribution, and control of the water content influenced the mechanical environment.

Dark red tongue color formation caused by hyperglycemia is attributed to decreased blood flow of tongue tissue partially due to nuclear factor-kappa B pathway activation.

OBJECTIVE: To investigate the potential mechanisms underlying the dark red tongue color formation induced by hyperglycemia. METHODS: A high-fat diet and intraperitoneal injection of streptozotocin were used to establish a diabetes model. The color and blood flow of tongues were analyzed by the Tongue Diagnosis Analysis System and laser Doppler flowmetry, respectively. Inflammatory factors and adhesion factors were measured in the circulation and tongue tissue by an enzyme-linked immunosorbent assay. Western blotting was employed to evaluate nuclear factor-kappa B (NF-κB) p50 and inhibitor of kappa B kinase protein expression levels in the tongue. Then, the NF-κB inhibitor, pyrrolidine dithiocarbamic acid ammonium salt was utilized to repress NF-κB pathway activation to validate that the NF-κB pathway plays a key role in blood flow and dark red tongue color formation. RESULTS: The diabetic rats displayed a dark red tongue color that was accompanied by NF-κB pathway activation and decreased blood flow in the tongue. These effects could be reversed by the NF-κB inhibitor. CONCLUSIONS: Our investigation demonstrated that hyperglycemia led to dark red tongue color formation by decreasing blood flow in the tongue, which was partly due to NF-κB pathway activation.

[Rare diseases in anesthesia : Knowledge mining and core points of perioperative anesthesiological care]. / Seltene Erkrankungen in der Anästhesie : Wissensbeschaffung und Kernpunkte der perioperativen anästhesiologischen Versorgung.

Due to refined and new diagnostic possibilities and improved medical care, in the future anesthesiologists will be more frequently confronted with patients suffering from rare diseases. As the physicians providing perioperative care often have little or no experience with the diseases of such patients, the access to high-quality specific literature is essential. In this respect they must be able to assess and classify the quality of the information which is predominantly available online, especially as when evidence-based knowledge is available, it is only available to a very limited extent. Patients with rare diseases mostly present with recurring problem constellations. A systematic assignment to the most important problem areas (airway, circulation, metabolism, etc.) as well as a structured and interdisciplinary approach are decisive for a successful perioperative treatment of these patients. Due to low prevalence, lack of personal experience and lack of evidence-based data, anesthesia in patients with SE is an absolute challenge, especially in time-critical situations.

Brain blood flow pulse analysis may help to recognize individuals who suffer from hydrocephalus.

BACKGROUND: Normal pressure hydrocephalus (NPH) is often associated with altered cerebral blood flow. Recent research with the use of the ultrasonic method suggests specific changes in the shape of cardiac-related cerebral arterial blood volume (CaBV) pulses in NPH patients. Our study aims to provide a quantitative analysis of the shape of CaBV pulses, estimated based on transcranial Doppler ultrasonography (TCD) in NPH patients and healthy individuals. METHODS: The CaBV pulses were estimated using TCD cerebral blood flow velocity signals recorded from probable NPH adults and age-matched healthy individuals at rest. The shape of the CaBV pulses was compared to a triangular shape with 27 similarity parameters calculated for every reliable CaBV pulse and compared between patients and volunteers. The diagnostic accuracy of the most prominent parameter for NPH classification was evaluated using the area under the receiver operating characteristic curve (AUC). RESULTS: The similarity parameters were calculated for 31 probable NPH patients (age: 59 years (IQR: 47, 67 years), 14 females) and 23 healthy volunteers (age: 54 years (IQR: 43, 61 years), 18 females). Eighteen of 27 parameters were different between healthy individuals and NPH patients (p < 0.05). The most prominent differences were found for the ascending slope of the CaBV pulse with the AUC equal to 0.87 (95% confidence interval: 0.77, 0.97, p < 0.001). CONCLUSIONS: The findings suggest that in NPH, the ascending slope of the CaBV pulse had a slower rise, was more like a straight line, and generally was less convex than in volunteers. Prospective research is required to verify the clinical utility of these findings.

Super-small zwitterionic micelles enable the improvement of blood-brain barrier crossing for efficient orthotopic glioblastoma combinational therapy.

Glioblastoma multiforme (GBM) remains incurable in clinical, nanotechnology-based drug delivery strategies show promising perspective in alleviating GBM, while limited blood-brain-barrier (BBB) permeation, short blood half-live accompanied by the poor tumor accumulation and penetration, significantly restrict the therapeutic outcomes. Herein, a versatile super-small zwitterionic nano-system (MCB(S)) based on carboxybetaine (CB) zwitterion functionalized hyperbranched polycarbonate (HPCB) is developed to overcome the brain delivery challenges. After grafting with amino-functionalized IR780 (free IR780), the ultimate paclitaxel (PTX)-encapsulated micelles (MCB(S)-IR@PTX) are precisely activated by near-infrared (NIR) for accelerated drug release and effective combinational GBM therapy. Importantly, MCB(S)-IR@PTX with the crosslinked structure and CB zwitterion prolongs blood-circulation, and CB-zwitterion further facilitates BBB-traversing through betaine/γ-aminobutyric acid (GABA) transporter-1 (BGT-1) pathway. Combined with the benefit of super small-size, MCB(S)-IR@PTX highly accumulates at tumor sites and penetrates deeply, thus efficiently inhibiting tumor growth and strikingly improving survival time in U87MG orthotopic GBM-bearing mouse model. The ingenious nanoplatform furnishes a versatile strategy for delivering therapeutics into the brain and realizing efficient brain cancer therapy.

Blood Circulation Assessment by Steadily Fluorescent Near-Infrared-II Aggregation-Induced Emission Nano Contrast Agents.

The dysfunction of the blood circulation system typically induces acute or chronic ischemia in limbs and vital organs, with high disability and mortality. While conventional tomographic imaging modalities have shown good performance in the diagnosis of circulatory diseases, multiple limitations remain for real-time and precise hemodynamic evaluation. Recently, fluorescence imaging in the second region of the near-infrared (NIR-II, 1000-1700 nm) has garnered great attention in monitoring and tracing various biological processes in vivo due to its advantages of high spatial-temporal resolution and real-time feature. Herein, we employed NIR-II imaging to carry out a blood circulation assessment by aggregation-induced emission fluorescent aggregates (AIE nano contrast agent, AIE NPs). Thanks to the longer excited wavelength, enhanced absorptivity, higher brightness in the NIR-II region, and broader optimal imaging window of the AIE NPs, we have realized a multidirectional assessment for blood circulation in mice with a single NIR-II imaging modality. Thus, our work provides a fluorescence contrast agent platform for accurate hemodynamic assessment.

Polysarcosine-Coated liposomes attenuating immune response induction and prolonging blood circulation.

HYPOTHESIS: Liposomes coated with long polysarcosine (PSar) chains at a high density might enable long blood circulation and attenuate accelerated blood clearance (ABC) phenomenon. EXPERIMENTS: In this study, we controlled the length (23, 45, 68 mers) and density (5, 10, 15 mol%) of PSar on liposomal coatings and, furthermore, investigated the effects of PSar length and density on the blood circulation time, biodistribution, immune response, and ABC phenomenon induction. Length-controlled PSar-bound lipids (PSar-PEs) were synthesized using a click reaction and inserted into bare liposomes at different combinations of chain lengths and proportions. FINDINGS: Although all PSar-coated liposomes (PSar-lipos) had similar morphological, physical, and chemical properties, they had different blood circulation times and biodistribution, and exerted varied effects on the immune system. All PSar-lipos with different PSar length and density showed a similar anti-PSar IgM response. Liposomes modified with the longest PSar chain (68 mers) at a high density (15 mol%) showed the longest blood circulation time and, additionally, attenuated ABC phenomenon compared with PEG-lipo. The ex vivo analysis of the biodistribution of liposomes revealed that a thick PSar layer enhanced the blood circulation time of liposomes due to the reduction of the accumulation of liposomes in the liver and spleen. These findings provide new insights into the relationship between IgM expression and ABC phenomenon inhibition.

Comparative Study of Nanoparticle Blood Circulation after Forced Clearance of Own Erythrocytes (Mononuclear Phagocyte System-Cytoblockade) or Administration of Cytotoxic Doxorubicin- or Clodronate-Loaded Liposomes.

Recent developments in the field of nanomedicine have introduced a wide variety of nanomaterials that are capable of recognizing and killing tumor cells with increased specificity. A major limitation preventing the widespread introduction of nanomaterials into the clinical setting is their fast clearance from the bloodstream via the mononuclear phagocyte system (MPS). One of the most promising methods used to overcome this limitation is the MPS-cytoblockade, which forces the MPS to intensify the clearance of erythrocytes by injecting allogeneic anti-erythrocyte antibodies and, thus, significantly prolongs the circulation of nanoagents in the blood. However, on the way to the clinical application of this approach, the question arises whether the induced suppression of macrophage phagocytosis via the MPS-cytoblockade could pose health risks. Here, we show that highly cytotoxic doxorubicin- or clodronate-loaded liposomes, which are widely used for cancer therapy and biomedical research, induce a similar increase in the nanoparticle blood circulation half-life in mice as the MPS-cytoblockade, which only gently and temporarily saturates the macrophages with the organism's own erythrocytes. This result suggests that from the point of view of in vivo macrophage suppression, the MPS-cytoblockade should be less detrimental than the liposomal anti-cancer drugs that are already approved for clinical application while allowing for the substantial improvement in the nanoagent effectiveness.

Supplementingand activating blood circulation method to treat vertebrobasilar dolichoectasia with posterior circulatory watershed infarction: a case report of two patients.

Vertebrobasilar dolichoectasia (VBD), a rare posterior circulation vascular variant disease, is an important risk factor for many acute cerebrovascular diseases. An insufficient understanding of VBD often leads to misdiagnose. Two cases of VBD that were initially diagnosed as posterior circulation watershed infarction are reported here. Absence of common causes of stroke including hypoperfusion, blood system diseases, carotid and aortic dissection, and eosinophil elevation, the symptoms of the 2 patients met the diagnostic criteria of VBD. Both patients displayed symptoms that were in line with the Traditional Chinese Medicine (TCM) syndrome pattern of "deficiency and blood stasis". Accordingly, they were comprehensively treated with Supplementingand activating blood circulation method. The clinical manifestations of the 2 patients were remarkably improved and no recurrence of watershed infarction was found in a 1-year follow-up. A detailed medical history and laboratory examination are capable of improving diagnostic accuracy of VBD. TCM treatment based on syndrome identification might be a promising candidate for VBD management.

Bioactive components and molecular mechanisms of Salvia miltiorrhiza Bunge in promoting blood circulation to remove blood stasis.

ETHNOPHARMACOLOGICAL RELEVANCE: Salvia miltiorrhiza Bunge (SM) is an outstanding herbal medicine with various traditional effects, especially promoting blood circulation to remove blood stasis. It has been widely used for centuries to treat blood stasis syndrome (BSS)-related diseases. BSS is one of the basic pathological syndromes of diseases such as cardiovascular and cerebrovascular diseases in traditional East Asian medicine, which is characterized by disturbance of blood circulation. However, the bioactive components and mechanisms of SM in the treatment of BSS have not been systematically reviewed. Therefore, this article outlines the anti-BSS effects of bioactive components of SM, concentrating on the molecular mechanisms. AIM OF THE REVIEW: To summarize the bioactive components of SM against BSS and highlight its potential targets and signaling pathways, hoping to provide a modern biomedical perspective to understand the efficacy of SM on enhancing blood circulation to remove blood stasis. MATERIALS AND METHODS: A comprehensive literature search was performed to retrieve articles published in the last two decades on bioactive components of SM used for BSS treatment from the online electronic medical literature database (PubMed). RESULTS: Phenolic acids and tanshinones in SM are the main bioactive components in the treatment of BSS, including but not limited to salvianolic acid B, tanshinone IIA, salvianolic acid A, cryptotanshinone, Danshensu, dihydrotanshinone, rosmarinic acid, protocatechuic aldehyde, and caffeic acid. They protect vascular endothelial cells by alleviating oxidative stress and inflammatory damage and regulating of NO/ET-1 levels. They also enhance anticoagulant and fibrinolytic capacity, inhibit platelet activation and aggregation, and dilate blood vessels. Moreover, lowering blood lipids and improving blood rheological properties may be the underlying mechanisms of their anti-BSS. More notably, these compounds play an anti-BSS role by mediating multiple signaling pathways such as Nrf2/HO-1, TLR4/MyD88/NF-κB, PI3K/Akt/eNOS, MAPKs (p38, ERK, and JNK), and Ca2+/K+ channels. CONCLUSIONS: Both phenolic acids and tanshinones in SM may act synergistically to target different signaling pathways to achieve the effect of promoting blood circulation.