[Research progress on anti-tumor effects by traditional Chinese medicine based on "soothing" or "blockage" regulation of tumor vessels].

Regulation of tumor vessels has become one of the most common strategies for clinical anti-tumor therapy. In recent years, studies have found that the anti-tumor effect of limotherapy, which routinely inhibits tumor angiogenesis, is not ideal and may even deteriorate the tumor microenvironment, causing tumor resistance and distal metastasis and increasing the risk of tumor metastasis and recurrence. However, the proper use of anti-angiogenic drugs can promote the normalization of tumor vessels, improve the structure and function of tumor vessels, increase the number of functional vessels in the tumor, and reduce the number of ineffective vessels. It is beneficial to promote the penetration of anti-tumor drugs into the tumor, improve the microenvironment of tumor hypoxia and immunosuppression, and enhance the anti-tumor effect. Traditional Chinese medicine(TCM) has a long history of understanding the etiology and pathogenesis of tumors and has accumulated rich experience in tumor treatment, with significant clinical advantages and broad application prospects. In this study, from the perspective of bidirectional "soothing" or "blockage" regulation of tumor vessels, the commonly used molecular targets were sorted out, and the research status of anti-tumor regulation of tumor vessels by monomer-single herb-compound(herb pair) of TCM in recent years was summarized. The research on the anti-tumor effects of TCM compounds and active ingredients by regulating tumor vessels combined with other therapies was analyzed and sorted out, so as to provide ideas for the clinical application of TCM in regulating functions and anti-tumor effects of tumor vessels.

Heterogeneous vasomotor responses in segments from Göttingen Minipigs coronary, cerebral, and mesenteric artery: A comparative study.

Göttingen Minipigs (GM) are used as an important preclinical model for cardiovascular safety pharmacology and for evaluation of cardiovascular drug targets. To improve the translational value of the GM model, the current study represents a basic characterization of vascular responses to endothelial regulators and sympathetic, parasympathetic, and sensory neurotransmitters in different anatomical origins. The aim of the current comparative and descriptive study is to use myography to characterize the vasomotor responses of coronary artery isolated from GM and compare the responses to those obtained from parallel studies using cerebral and mesenteric arteries. The selected agonists for sympathetic (norepinephrine), parasympathetic (carbachol), sensory (calcitonin gene-related peptide, CGRP), and endothelial pathways (endothelin-1, ET-1, and bradykinin) were used for comparison. Further, the robust nature of the vasomotor responses was evaluated after 24 h of cold storage of vascular tissue mimicking the situation under which human biopsies are often kept before experiments or grafting is feasible. Results show that bradykinin and CGRP consistently dilated, and endothelin consistently contracted artery segments from coronary, cerebral, and mesenteric origin. By comparison, norepinephrine and carbachol, had responses that varied with the anatomical source of the tissues. To support the basic characterization of GM vasomotor responses, we demonstrated the presence of mRNA encoding selected vascular receptors (CGRP- and ETA-receptors) in fresh artery segments. In conclusion, the vasomotor responses of isolated coronary, cerebral, and mesenteric arteries to selected agonists of endothelial, sympathetic, parasympathetic, and sensory pathways are different and the phenotypes are similar to sporadic human findings.

GRGB rPPG: An Efficient Low-Complexity Remote Photoplethysmography-Based Algorithm for Heart Rate Estimation.

Remote photoplethysmography (rPPG) is a promising contactless technology that uses videos of faces to extract health parameters, such as heart rate. Several methods for transforming red, green, and blue (RGB) video signals into rPPG signals have been introduced in the existing literature. The RGB signals represent variations in the reflected luminance from the skin surface of an individual over a given period of time. These methods attempt to find the best combination of color channels to reconstruct an rPPG signal. Usually, rPPG methods use a combination of prepossessed color channels to convert the three RGB signals to one rPPG signal that is most influenced by blood volume changes. This study examined simple yet effective methods to convert the RGB to rPPG, relying only on RGB signals without applying complex mathematical models or machine learning algorithms. A new method, GRGB rPPG, was proposed that outperformed most machine-learning-based rPPG methods and was robust to indoor lighting and participant motion. Moreover, the proposed method estimated the heart rate better than well-established rPPG methods. This paper also discusses the results and provides recommendations for further research.

Research progress on anti-tumor effects by traditional Chinese medicine based on "soothing" or "blockage" regulation of tumor vessels / 中国中药杂志

Regulation of tumor vessels has become one of the most common strategies for clinical anti-tumor therapy. In recent years, studies have found that the anti-tumor effect of limotherapy, which routinely inhibits tumor angiogenesis, is not ideal and may even deteriorate the tumor microenvironment, causing tumor resistance and distal metastasis and increasing the risk of tumor metastasis and recurrence. However, the proper use of anti-angiogenic drugs can promote the normalization of tumor vessels, improve the structure and function of tumor vessels, increase the number of functional vessels in the tumor, and reduce the number of ineffective vessels. It is beneficial to promote the penetration of anti-tumor drugs into the tumor, improve the microenvironment of tumor hypoxia and immunosuppression, and enhance the anti-tumor effect. Traditional Chinese medicine(TCM) has a long history of understanding the etiology and pathogenesis of tumors and has accumulated rich experience in tumor treatment, with significant clinical advantages and broad application prospects. In this study, from the perspective of bidirectional "soothing" or "blockage" regulation of tumor vessels, the commonly used molecular targets were sorted out, and the research status of anti-tumor regulation of tumor vessels by monomer-single herb-compound(herb pair) of TCM in recent years was summarized. The research on the anti-tumor effects of TCM compounds and active ingredients by regulating tumor vessels combined with other therapies was analyzed and sorted out, so as to provide ideas for the clinical application of TCM in regulating functions and anti-tumor effects of tumor vessels.

How abundant are superoxide and hydrogen peroxide in the vasculature lumen, how far can they reach?

Paracrine superoxide (O2•-) and hydrogen peroxide (H2O2) signaling critically depends on these substances' concentrations, half-lives and transport ranges in extracellular media. Here we estimated these parameters for the lumen of human capillaries, arterioles and arteries using reaction-diffusion-advection models. These models considered O2•- and H2O2 production by endothelial cells and uptake by erythrocytes and endothelial cells, O2•- dismutation, O2•- and H2O2 diffusion and advection by the blood flow. Results show that in this environment O2•- and H2O2 have half-lives <60. ms and <40. ms, respectively, the former determined by the plasma SOD3 activity, the latter by clearance by endothelial cells and erythrocytes. H2O2 concentrations do not exceed the 10 nM scale. Maximal O2•- concentrations near vessel walls exceed H2O2's several-fold when the latter results solely from O2•- dismutation. Cytosolic dismutation of inflowing O2•- may thus significantly contribute to H2O2 delivery to cells. O2•- concentrations near vessel walls decay to 50% of maximum 12 µm downstream from O2•- production sites. H2O2 concentrations in capillaries decay to 50% of maximum 22 µm (6.0 µm) downstream from O2•- (H2O2) production sites. Near arterioles' (arteries') walls, they decay by 50% within 6.0 µm (4. µm) of H2O2 production sites. However, they reach maximal values 50 µm (24 µm) downstream from O2•- production sites and decrease by 50% over 650 µm (500 µm). Arterial/olar endothelial cells might thus signal over a mm downstream through O2•--derived H2O2, though this requires nM-sensitive H2O2 transduction mechanisms.

Effectiveness of Remote PPG Construction Methods: A Preliminary Analysis.

The contactless recording of a photoplethysmography (PPG) signal with a Red-Green-Blue (RGB) camera is known as remote photoplethysmography (rPPG). Studies have reported on the positive impact of using this technique, particularly in heart rate estimation, which has led to increased research on this topic among scientists. Therefore, converting from RGB signals to constructing an rPPG signal is an important step. Eight rPPG methods (plant-orthogonal-to-skin (POS), local group invariance (LGI), the chrominance-based method (CHROM), orthogonal matrix image transformation (OMIT), GREEN, independent component analysis (ICA), principal component analysis (PCA), and blood volume pulse (PBV) methods) were assessed using dynamic time warping, power spectrum analysis, and Pearson's correlation coefficient, with different activities (at rest, during exercising in the gym, during talking, and while head rotating) and four regions of interest (ROI): the forehead, the left cheek, the right cheek, and a combination of all three ROIs. The best performing rPPG methods in all categories were the POS, LGI, and OMI methods; each performed well in all activities. Recommendations for future work are provided.

Stromal Transcription Factor 21 Regulates Development of the Renal Stroma via Interaction with Wnt/ß-Catenin Signaling.

Background: Kidney formation requires coordinated interactions between multiple cell types. Input from the interstitial progenitor cells is implicated in multiple aspects of kidney development. We previously reported that transcription factor 21 (Tcf21) is required for ureteric bud branching. Here, we show that Tcf21 in Foxd1+ interstitial progenitors regulates stromal formation and differentiation via interaction with ß-catenin. Methods: We utilized the Foxd1Cre;Tcf21f/f murine kidney for morphologic analysis. We used the murine clonal mesenchymal cell lines MK3/M15 to study Tcf21 interaction with Wnt/ß-catenin. Results: Absence of Tcf21 from Foxd1+ stromal progenitors caused a decrease in stromal cell proliferation, leading to marked reduction of the medullary stromal space. Lack of Tcf21 in the Foxd1+ stromal cells also led to defective differentiation of interstitial cells to smooth-muscle cells, perivascular pericytes, and mesangial cells. Foxd1Cre;Tcf21f/f kidney showed an abnormal pattern of the renal vascular tree. The stroma of Foxd1Cre;Tcf21f/f kidney demonstrated marked reduction in ß-catenin protein expression compared with wild type. Tcf21 was bound to ß-catenin both upon ß-catenin stabilization and at basal state as demonstrated by immunoprecipitation in vitro. In MK3/M15 metanephric mesenchymal cells, Tcf21 enhanced TCF/LEF promoter activity upon ß-catenin stabilization, whereas DNA-binding deficient mutated Tcf21 did not enhance TCF/LEF promoter activity. Kidney explants of Foxd1Cre;Tcf21f/f showed low mRNA expression of stromal Wnt target genes. Treatment of the explants with CHIR, a Wnt ligand mimetic, restored Wnt target gene expression. Here, we also corroborated previous evidence that normal development of the kidney stroma is required for normal development of the Six2+ nephron progenitor cells, loop of Henle, and the collecting ducts. Conclusions: These findings suggest that stromal Tcf21 facilitates medullary stroma development by enhancing Wnt/ß-catenin signaling and promotes stromal cell proliferation and differentiation. Stromal Tcf21 is also required for the development of the adjacent nephron epithelia.

Optic nerve head astrocytes contribute to vascular associated effects.

Purpose: This study was conducted in order to test the expression of vasoactive substances within rat lamina cribrosa (LC) and optic nerve head (ONH) astrocytes, so as to investigate the role and potential mechanism of ONH astrocytes in vascular associated effects. Methods: LC tissue sections and primary cultured ONH astrocytes were obtained from adult Sprague-Dawley (SD) rats. Immunofluorescent staining was then used to detect the expression of vasoactive substances. Hyperoxia exposure was carried out both in vivo and in vitro, after which nitric oxide (NO) levels in LC tissue and cell supernatant were detected. The variations of protein and gene expression associated with vasoactive substances were subsequently tested. ONH astrocytes and vascular smooth muscle cells (VSMCs) were then incubated in a direct co-culture manner. Morphological parameters of VSMCs were finally analyzed in order to evaluate cell contraction. Results: Endothelin-1 (ET-1), nitric oxide synthase (NOS) and renin-angiotensin system (RAS) were detected in both LC tissue and ONH astrocytes. Retinal vessel diameter was found obviously decreased following hyperoxia exposure. Moreover, hyperoxia inhibited NO production both in vivo and in vitro. ET-1 and RAS elements were observed to be upregulated, whereas NOS was downregulated. In ONH astrocytes and VSMCs co-culture system, the length-to-width ratio of VSMCs was shown to significantly increase on days 3 and 7 in hyperoxia compared with normoxia. Conclusions: There is an abundance of expression of vasoactive substances within LC tissue and ONH astrocytes. The contractile response of VSMCs in the co-culture system provided direct evidence for the involvement of ONH astrocytes in vascular associated effects, which may signify a potentially novel direction for future research.

Microglia: Active participants in brain capillary function.

A recent study by Bisht, Okojie, and Sharma, et al. characterizes a population of capillary-associated microglia (CAM) whose cell bodies are positioned along small blood vessels in the healthy mouse brain. Through elegant, longitudinal intravital imaging of brain vasculature and CAMs, the authors have uncovered the significance of microglia in cerebral blood flow regulation. Further investigation into the functions of this CAM population and how they interact with surrounding cells within the neurovascular unit will improve our understanding of vascular regulation and cerebrovascular diseases.

Blood Flow Regulates Glomerular Capillary Formation in Zebrafish Pronephros.

Background: The renal glomerulus is a tuft of capillaries in Bowman's capsule and functions as a blood-filtration unit in the kidney. The unique glomerular capillary tuft structure is relatively conserved through vertebrate species. However, the morphogenetic mechanism governing glomerular capillary tuft formation remains elusive. Methods: To clarify how glomerular capillaries develop, we analyzed glomerular capillary formation in the zebrafish pronephros by exploiting fluorescence-based bio-imaging technology. Results: During glomerular capillary formation in the zebrafish pronephros, endothelial cells initially sprouted from the dorsal aorta and formed the capillaries surrounding the bilateral glomerular primordia in response to podocyte progenitor-derived vascular endothelial growth factor-A. After formation, blood flow immediately occurred in the glomerular primordia-associated capillaries, while in the absence of blood flow, they were transformed into sheet-like structures enveloping the glomerular primordia. Subsequently, blood flow induced formation of Bowman's space at the lateral sides of the bilateral glomerular primordia. Concomitantly, podocyte progenitors enveloped their surrounding capillaries while moving toward and coalescing at the midline. These capillaries then underwent extensive expansion and remodeling to establish a functional glomerular capillary tuft. However, stopping blood flow inhibited the remodeling of bilateral glomerular primordia, which therefore remained unvascularized but covered by the vascular sheets. Conclusions: We delineated the morphogenetic processes governing glomerular capillary tuft formation in the zebrafish pronephros and demonstrated crucial roles of blood flow in its formation. Blood flow maintains tubular structures of the capillaries surrounding the glomerular primordia and promotes glomerular incorporation of these vessels by inducing the remodeling of glomerular primordia.

Alpha Globin Gene Copy Number Is Associated with Prevalent Chronic Kidney Disease and Incident End-Stage Kidney Disease among Black Americans.

BACKGROUND: α-Globin is expressed in endothelial cells of resistance arteries, where it limits endothelial nitric oxide signaling and enhances α-adrenergic-mediated vasoconstriction. α-Globin gene (HBA) copy number is variable in people of African descent and other populations worldwide. Given the protective effect of nitric oxide in the kidney, we hypothesized that HBA copy number would be associated with kidney disease risk. METHODS: Community-dwelling Black Americans aged ≥45 years old were enrolled in a national longitudinal cohort from 2003 through 2007. HBA copy number was measured using droplet digital PCR. The prevalence ratio (PR) of CKD and the relative risk (RR) of incident reduced eGFR were calculated using modified Poisson multivariable regression. The hazard ratio (HR) of incident ESKD was calculated using Cox proportional hazards multivariable regression. RESULTS: Among 9908 participants, HBA copy number varied from 2 to 6. In analyses adjusted for demographic, clinical, and genetic risk factors, a one-copy increase in HBA was associated with 14% greater prevalence of CKD (PR, 1.14; 95% CI, 1.07 to 1.21; P<0.0001). While HBA copy number was not associated with incident reduced eGFR (RR, 1.06; 95% CI, 0.94 to 1.19; P=0.38), the hazard of incident ESKD was 32% higher for each additional copy of HBA (HR, 1.32; 95% CI, 1.09 to 1.61; P=0.005). CONCLUSIONS: Increasing HBA copy number was associated with a greater prevalence of CKD and incidence of ESKD in a national longitudinal cohort of Black Americans.

Non-Coding RNAs in COVID-19: Emerging Insights and Current Questions.

The highly infectious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged as the causative agent of coronavirus disease 2019 (COVID-19) in late 2019, igniting an unprecedented pandemic. A mechanistic picture characterising the acute immunopathological disease in severe COVID-19 is developing. Non-coding RNAs (ncRNAs) constitute the transcribed but un-translated portion of the genome and, until recent decades, have been undiscovered or overlooked. A growing body of research continues to demonstrate their interconnected involvement in the immune response to SARS-CoV-2 and COVID-19 development by regulating several of its pathological hallmarks: cytokine storm syndrome, haemostatic alterations, immune cell recruitment, and vascular dysregulation. There is also keen interest in exploring the possibility of host-virus RNA-RNA and RNA-RBP interactions. Here, we discuss and evaluate evidence demonstrating the involvement of short and long ncRNAs in COVID-19 and use this information to propose hypotheses for future mechanistic and clinical studies.

Nanodrug Delivery Systems Modulate Tumor Vessels to Increase the Enhanced Permeability and Retention Effect.

The use of nanomedicine for antitumor therapy has been extensively investigated for a long time. Enhanced permeability and retention (EPR) effect-mediated drug delivery is currently regarded as an effective way to bring drugs to tumors, especially macromolecular drugs and drug-loaded pharmaceutical nanocarriers. However, a disordered vessel network, and occluded or embolized tumor blood vessels seriously limit the EPR effect. To augment the EPR effect and improve curative effects, in this review, we focused on the perspective of tumor blood vessels, and analyzed the relationship among abnormal angiogenesis, abnormal vascular structure, irregular blood flow, extensive permeability of tumor vessels, and the EPR effect. In this commentary, nanoparticles including liposomes, micelles, and polymers extravasate through the tumor vasculature, which are based on modulating tumor vessels, to increase the EPR effect, thereby increasing their therapeutic effect.

Hypoxia response element-directed expression of bFGF in dental pulp stem cells improve the hypoxic environment by targeting pericytes in SCI rats.

Cell-based transplantation strategies possess great potential for spinal cord injury (SCI) repair. Basic fibroblast growth factor (bFGF) has been reported to have multiple neuro-promoting effects on developing and adult nervous system of mammals and considered a promising therapy for nerve injury following SCI. Human dental pulp stem cells (DPSCs) are abundant stem cells with low immune rejection, which can be considered for cell replacement therapy. The purpose of this study was to investigate the roles of DPSCs which express bFGF under the regulation of five hypoxia-responsive elements (5HRE) using an adeno-associated virus (AAV-5HRE-bFGF-DPSCs) in SCI repairing model. In this study, DPSCs were revealed to differentiate into CD13+ pericytes and up-regulate N-cadherin expression to promote the re-attachment of CD13+ pericytes to vascular endothelial cells. The re-attachment of CD13+ pericytes to vascular endothelial cells subsequently increased the flow rate of blood in microvessels via the contraction of protuberance. As a result, increased numbers of red blood cells carried more oxygen to the damaged area and the local hypoxia microenvironment in SCI was improved. Thus, this study represents a step forward towards the potential use of AAV-5HRE-bFGF-DPSCs in SCI treatment in clinic.

Comprehensive Assessment of Fluid Status by Point-of-Care Ultrasonography.

The management of complex fluid and electrolyte disorders is central to the practice of nephrologists. The sensitivity of physical examination alone to determine fluid status is limited, precluding accurate clinical decision making. Point-of-care ultrasonography (POCUS) is emerging as a valuable, noninvasive, bedside diagnostic tool for objective evaluation of physiologic and hemodynamic parameters related to fluid status, tolerance, and responsiveness. Rapid bedside sonographic evaluation can obtain qualitative data on cardiac function and quantitative data on pulmonary congestion. Advanced POCUS, including goal-directed Doppler echocardiography, provides additional quantitative information, including flow velocities and pressures across the cardiac structures. Recently, abnormal Doppler flow patterns in abdominal organs secondary to increased right atrial pressure have been linked to congestive organ damage, adding another component to the hemodynamic assessment. Integrating POCUS findings with clinical and laboratory data can further elucidate a patient's hemodynamic status. This drives decisions regarding crystalloid administration or, conversely, diuresis or ultrafiltration and allows tailored therapy for individual patients. In this article, we provide an overview of the focused assessment of cardiovascular function and pulmonary and venous congestion using POCUS and review relevant literature.

Distribution of Nogo in the heart and its role in cardiovascular disease / 解剖学报

As a member of the reticulin family, Nogo is mainly involved in processes such as tissue regeneration, apoptosis and tumor growth after tissue injury. Cardiovascular disease is one of the main diseases that threaten human health at present. In recent years, research on Nogo in the cardiovascular system has become increasingly extensive. Changes in the expression of Nogo during myocardial fibrosis, myocardial cell apoptosis and vascular remodeling suggest that it may play a certain role. This article reviews the distribution of Nogo in the heart and its role in cardiovascular disease, in order to reveal its possible role and mechanism in cardiovascular diseases.

Pulse Wave Analysis and Pulse Wave Velocity for Fistula Assessment.

BACKGROUND/AIMS: Pulse wave analysis (PWA) and pulse wave velocity (PWV) provide information about arterial stiffness and elasticity, which is mainly used for cardiovascular risk stratification. In the presented prospective observational pilot study, we examined the hypothesis that radiocephalic fistula (RCF)-related changes of haemodynamics and blood vessel morphology including high as well as low flow can be seen in specific changes of pulse wave (PW) morphology. METHODS: Fifty-six patients with RCF underwent local ambilateral peripheral PWA and PWV measurement with the SphygmoCor® device. Given that the output parameters of the SphygmoCor® are not relevant for the study objectives, we defined new suitable parameters for PWA in direct proximity to fistulas and established an appropriate analysing algorithm. Duplex sonography served as reference method. RESULTS: Marked changes of peripheral PW morphology when considering interarm differences of slope and areas between the fistula and non-fistula arms were observed in the Arteria radialis, A. brachialis and arterialized Vena cephalica. The sum of the slope differences was found to correlate with an increased flow, while in patients with fistula failure no changes in PW morphology were seen. Moreover, PWV was significantly reduced in the fistula arm. CONCLUSION: Beside duplex sonography, ambilateral peripheral PWA and PWV measurements are potential new clinical applications to characterize and monitor RCF function, especially in terms of high and low flow.

Using the prone position could help to combat the development of fast hypoxia in some patients with COVID-19.

The world is facing an explosive COVID-19 pandemic. Some cases rapidly develop deteriorating lung function, which causes deep hypoxaemia and requires urgent treatment. Many centres have started treating patients in the prone position, and oxygenation has improved considerably in some cases. Questions have been raised regarding the mechanisms behind this. The mini review provides some insights into the role of supine and prone body positions and summarises the latest understanding of the responsible mechanisms. The scope for discussion is outside the neonatal period and entirely based on experimental and clinical experiences related to adults. The human respiratory system is a complex interplay of many different variables. Therefore, this mini review has prioritised previous and ongoing research to find explanations based on three scientific areas: gravity, lung structure and fractal geometry and vascular regulation. It concludes that gravity is one of the variables responsible for ventilation/perfusion matching but in concert with lung structure and fractal geometry, ventilation and regulation of lung vascular tone. Since ventilation distribution does not change between supine and prone positions, the higher expression of nitric oxide in dorsal lung vessels than in ventral vessels is likely to be the most important mechanism behind enhanced oxygenation in the prone position.