Structure Of Blood Vessels Research Articles

The microfluidic artificial lung: Mimicking nature's blood path design to solve the biocompatibility paradox.

The increasing prevalence of chronic lung disease worldwide, combined with the emergence of multiple pandemics arising from respiratory viruses over the past century, highlights the need for safer and efficacious means for providing artificial lung support. Mechanical ventilation is currently used for the vast majority of patients suffering from acute and chronic lung failure, but risks further injury or infection to the patient's already compromised lung function. Extracorporeal membrane oxygenation (ECMO) has emerged as a means of providing direct gas exchange with the blood, but limited access to the technology and the complexity of the blood circuit have prevented the broader expansion of its use. A promising avenue toward simplifying and minimizing complications arising from the blood circuit, microfluidics-based artificial organ support, has emerged over the past decade as an opportunity to overcome many of the fundamental limitations of the current standard for ECMO cartridges, hollow fiber membrane oxygenators. The power of microfluidics technology for this application stems from its ability to recapitulate key aspects of physiological microcirculation, including the small dimensions of blood vessel structures and gas transfer membranes. An even greater advantage of microfluidics, the ability to configure blood flow patterns that mimic the smooth, branching nature of vascular networks, holds the potential to reduce the incidence of clotting and bleeding and to minimize reliance on anticoagulants. Here, we summarize recent progress and address future directions and goals for this potentially transformative approach to artificial lung support.

Analysis of Heat Dissipation Performance of Battery Liquid Cooling Plate Based on Bionic Structure

To provide a favorable temperature for a power battery liquid cooling system, a bionic blood vessel structure of the power battery liquid cooling plate is designed based on the knowledge of bionics and the human blood vessel model. For three different discharge rates of 1C, 2C, and 3C, FLUENT is used to simulate and analyze the heat dissipation performance of the liquid cooling plate with a bionic vascular structure. The influence of the pipe distance (A1 and A2) at the coolant outlet, the thickness of the liquid cooling plate, the inner pipe turning radius R of the pipe in the channel, and the mass flow of coolant on the heat dissipation performance are studied. The results show that the pipe distance (A1 and A2), plate thickness, and inner pipe turning radius R have significant effects on the heat dissipation of the liquid cooling plate, especially under a 3C discharge. In addition, the channel area at the coolant outlet also has great influence on the heat dissipation performance of the liquid cooling plate, and the variable width optimization of the channel area at the outlet greatly improves the heat dissipation performance of the liquid cooling plate. Increasing the inlet mass flow rate can improve the heat dissipation capacity, but at the expense of a pressure drop. A verification experiment is designed for 3C discharge. The results show that the error between the experiment and simulation results is within 9.8%; therefore, the simulation is accurate, and the liquid cooling plate has a significant heat dissipation effect.

Gelatin/sodium alginate hydrogel-coated decellularized porcine coronary artery to construct bilayer tissue engineered blood vessels

Cardiovascular diseases and vascular trauma can be commonly found in the population. Scholars worldwide hope to develop small-diameter vascular grafts that can replace autologous vessels for clinical use. Decellularized blood vessels can retain the original morphology, structure, and physical properties of blood vessels, which is conducive to cell growth, proliferation, and differentiation. In this study, porcine coronary arteries (PCAs) were decellularized to prepare decellularized porcine coronary artery (DPCA), and bilayer hybrid scaffolds were prepared by coating gelatin and sodium alginate mixed hydrogel of seven different proportions and combined with mouse fibroblasts (L929 cells) to study the construction of tissue engineering vessels in vitro. The obtained bilayer hybrid scaffolds were 3–7 cm in length, 5 mm in external diameter, and 1 mm in average wall thickness. All seven bilayer hybrid scaffolds showed good biocompatibility after cell inoculation. Compared with 2D culture, cells on 3D scaffolds grew relatively slowly in the first 4 days, and the number of cells proliferated rapidly at 7 days. In the same culture days, different concentrations of hydrogel also had an impact on cell proliferation. With the increase of hydrogel content, cells on the 3D scaffold formed cell colonies faster. The results showed that the scaffold had good biocompatibility and could meet the needs of artificial blood vessel construction.

Retinal Blood Vessel Segmentation Using a Generalized Gamma Probability Distribution Function (PDF) of Matched Filtered

Retinal images contain information about the retina's blood vessel structure to predict retinal diseases such as diabetics, obesity, glaucoma, etc. Segmentation of accurate retinal blood vessels is a challenging task in the low background of retinal images. Therefore, we proposed a Generalized Gamma Distribution probability distribution function (pdf) to extract the accurate vascular structure on the retinal images. The proposed approach is divided into processing steps, the Generalized Gamma distribution kernel, and the postprocessing step. In pre-processing, the conversion of a color retinal image into a grayscale image using PCA followed by the CLAHE method and the Toggle Contrast method enhances the grayscale images of the retina. The proposed matched filter of Generalized Gamma distribution generates the MFR images. The postprocessing step extracts the thick vessels and thin retinal blood vessels using the optimal thresholding technique. The results obtained on DIRVE database average accuracy 95.00% and the STARE database 93.85%, respectively.

Notch signaling regulates vessel structure and function via Hspg2

The abnormal structure of tumor blood vessels is an important reason for the low efficacy of anti-tumor drugs. Notch signaling is an evolutionarily highly conserved signaling pathway that plays an important role in vessel development. However, the role and mechanism of Notch signaling in the formation of vascular structure is not fully understood. In this study, we demonstrated that blocking Notch signaling in endothelial cells (ECs) leads to obstructed tumor blood vessel basement membrane formation and the reduction of blood perfusion, as well as blood-retinal barrier (BRB) and blood-brain barrier (BBB) destruction in healthy mice. Endothelial Notch overactivation exacerbates the increases in tumor blood vessel basement membrane and blood perfusion ratio, and promotes recruitment of retinal vascular smooth muscle cells in neonatal mice. Notch signaling also regulates the formation of adhesion junctions (AJs) in ECs. In addition, we confirmed that Notch signaling regulates the AJs of ECs by regulating the expression of downstream gene Hspg2. This research is of great theoretical and practical significance for understanding the mechanism of tumor vascular structure formation as well as the search for new targets for vascular-targeted therapy.

Bioinspired poly (ionic liquid) membrane for efficient salinity gradient energy harvesting: Electrostatic crosslinking induced hierarchical nanoporous network

The development and utilization of salinity gradient energy are of great significance to the carbon-neutral strategic demand for clean energy in the new era. Conventional ion-exchange membranes have been employed to recover this wide-distributed energy by reverse electrodialysis membrane processes, however, the dense membrane structure and chemical instability limit the ionic transport in various working environments. Here, inspired by the rapid mass transport caused by the hierarchical structure of blood vessels, we employ two types of polyelectrolytes to fabricate a bioinspired three-dimensional interconnect porous membrane by simply casting-soaking, and this membrane shows great chemical stability due to the ionic crossing enhancement. The interconnected nanoporous structure and the enriched surface functional groups of the membrane render the high-performance osmotic energy conversion from different resources, including the Gibbs free energy between seawater and riverwater, commonly used organic solvents, and also in the solution treatment process of spent batteries. We believe this chemical-stable, nanoporous and freestanding membrane might take one more step towards practical applications and membrane technology.

Pathogenetic Mechanisms of Hypertension-Brain-Induced Complications: Focus on Molecular Mediators.

There is growing evidence that hypertension is the most important vascular risk factor for the development and progression of cardiovascular and cerebrovascular diseases. The brain is an early target of hypertension-induced organ damage and may manifest as stroke, subclinical cerebrovascular abnormalities and cognitive decline. The pathophysiological mechanisms of these harmful effects remain to be completely clarified. Hypertension is well known to alter the structure and function of cerebral blood vessels not only through its haemodynamics effects but also for its relationships with endothelial dysfunction, oxidative stress and inflammation. In the last several years, new possible mechanisms have been suggested to recognize the molecular basis of these pathological events. Accordingly, this review summarizes the factors involved in hypertension-induced brain complications, such as haemodynamic factors, endothelial dysfunction and oxidative stress, inflammation and intervention of innate immune system, with particular regard to the role of Toll-like receptors that have to be considered dominant components of the innate immune system. The complete definition of their prognostic role in the development and progression of hypertensive brain damage will be of great help in the identification of new markers of vascular damage and the implementation of innovative targeted therapeutic strategies.

Abstract P5-18-12: Cardioprotective effects of walnuts against aromatase inhibitor: Pilot study in a zebrafish model

Abstract BACKGROUND: Breast cancer patients on aromatase inhibitor (AI) are at a significantly higher risk of heart failure and cardiovascular disease (CVD) compared with patients on tamoxifen, and trend toward increased risks of myocardial infarction and ischemic stroke. In a clinical setting, AI has been shown to induce endothelial dysfunction that is a predictor of CVD. Further, patients on extended AI therapy exhibit significantly higher number of cardiovascular events when compared with patients who took AI for no longer than 5 years. AI effects on cardiovascular health may reflect the expression of functional estrogen receptors (ERs) in vascular endothelial and smooth muscle cells and cardiomyocytes, especially the membrane bound G-protein coupled ER (GPER). Activation of nuclear ER causes enhanced vasorelaxation and re-endovascularization, whilst GPER has been identified as a mediator of estrogen-induced vasodilation, either acting through nitric oxide (NO) or independent of it. GPER activation also protects against cholesterol-induced endothelial changes and endothelial inflammation. Since walnuts and walnut oil have many cardioprotective properties, we investigated if walnuts might prevent adverse effects of AI on a zebrafish model. Walnuts are rich in plant-derived n-3 PUFA alpha-linolenic acid (ALA).METHODS: Zebrafish embryos are used in cardiotoxicity studies (reduction of heartbeat) to model various human diseases. It has been shown that at 72 hours post fertilization (hpf) the primary and sprout vessels in the zebrafish embryo heart become active, and the blood vessel structure closely resembles of that in the human body. In our study, zebrafish embryos were treated with 4 mL of corn oil, soybean oil, docosahexaenoic acid (DHA) added to soybean oil, walnut oil or walnut powder added to walnut oil when they were 24 hpf. Oils were administered to yolk sac. 10-500 mM letrozole was added to water when fish were 48 hpf, and finally heart beat was measured from 72 hpf embryos. For the heart beat measurements, zebrafish embryos were anesthetized, and recorded to calculate the heart rate. After zebrafish was euthanized, RNA and protein were collected to assess changes in Esr2a, Esr2b, Gper1, Nos1, Nos2a, and Nos2b (shares properties with Nos3/eNOS). RESULTS: Administration of 500 mM letrozole significantly (p<0.001) reduced the heartbeat in zebrafish, indicating that it impaired cardiac function. None of the oils significantly altered the heartbeat, compared with controls. However, both walnut oil (p<0.006) and walnut powder enriched walnut oil (p<0.001) increased heartbeat in letrozole treated zebrafish, compared with zebrafish only given letrozole. Thus, walnuts prevented letrozole induced reduction in heartbeat. RT-qPCR analysis indicated that letrozole significantly reduced Gper (p<0.001) levels. Walnut oil prevented this change. Walnut oil also caused a significant reduction in Nos1 (p=0.014) levels during letrozole treatment. The effect of walnut powder on gene expression has not yet been studied.CONCLUSIONS: Although preliminary, our data suggest that walnuts might be cardioprotective during letrozole treatment. The protective effect may be mediated by prevention of letrozole-induced inhibition of GPER which acts as a vasodilator in the vasculature and cardiomyocytes. Future studies are planned to investigate if feeding adult zebrafish walnut powder and/or walnut oil has cardioprotective effects against chronic letrozole administration, whether GPER is the mediator of these effects, and if GPER acts through activating pathways such as EGFR, ERK, PI3K/Akt and cAMP/PKA. Further, the possibility that walnuts might either adversely or beneficially affect AIs’ effects on breast cancer will be studied. Citation Format: Leena Hilakivi-Clarke, Joas Lucas Da Silva, Anne Blaes, Luke Hoeppner. Cardioprotective effects of walnuts against aromatase inhibitor: Pilot study in a zebrafish model [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P5-18-12.

Facial Injections and Blindness: A Review on Anatomy.

With the sudden emergence of new medical aesthetic fillers, the number of fillers injected worldwide has exploded, but there are also worrying risks in the pursuit of beauty. At present, many cases of blindness caused by injection of aesthetic fillers have been reported. Most of the cases are caused by irreversible vascular embolism. This is a rare yet greatly feared complication of using facial cosmetic fillers. This article reviewed and analyzed the literature and summarized the changes in the anatomical structure of facial blood vessels related to blindness during facial injection.

Dioscin Reduces Vascular Damage in the Retina of db/db Mice by Inhibiting the VEGFA Signaling Pathway.

Diabetic retinopathy (DR) is a complication of diabetes that has a serious impact on the quality of life of patients. VEGFA is necessary in the physiological state to maintain endothelial activity and physical properties of blood vessels. VEGFA plays an important role in the promotion of neovascularization; therefore, inhibition of VEGFA can degrade the structure of blood vessels and reduce neovascularization. In the present study, HERB, a high-throughput experimental and reference-oriented database of herbal medicines, was used for compound mining targeting VEGFA. The compounds most likely to interact with VEGFA were screened by molecular docking. Next, the compounds were used to verify whether it could inhibit the activity of the VEGF signaling pathway in vitro and neovascularization in vivo. In vitro, we found that dioscin could inhibit the activation of the VEGFA–VEGFR2 signaling pathway and cell proliferation of human retinal microvascular endothelial cells in a high-glucose (HG) environment. A more important dioscin intervention inhibits the expression of pro-angiogenic factors in the retinas of db/db mice. In conclusion, our study indicates that dioscin reduces the vascular damage and the expression of pro-angiogenic factors in the retina of db/db mice and implies an important and potential application of dioscin for treatment of DR in clinics.

Establishment of Standard Human Blood Vessel Model Based on Image Registration and Fitting Technology

PurposeThe blood vessel gives key information for pathological changes in a variety of diseases. In view of the crucial role of blood vessel structure, the present study aims to establish a digital human blood vessel standard model for diagnosing blood vessel-related diseases.MethodsThe present study recruited eight healthy volunteers, and reconstructed their bilateral upper extremity arteries according to CTA. The reconstructed vessels were segmented, registered, and merged into a bunch. After being cut by continuous cut planes, the dispersion of the blood vessel bunches on each cut plane were calculated.ResultsThe results demonstrated that the middle segment of the brachial artery, the proximal segment of the ulnar artery, and the middle and distal segments of the radial artery had a low degree of dispersion. A standard blood vessel model was finally established by the integral method using the low-dispersion segments above. The accuracy of the standard blood vessel model was also verified by an actual contralateral vessel, which revealed that the deviation between the model and the actual normal contralateral brachial artery was relatively small.ConclusionThe structure of the model was highly accordant with the real ones, which can be of great help in evaluating the blood vessel changes in blood vessel-related diseases, bone and soft-tissue tumors, and creating accurate surgical plans.

Blood vessel tail artifacts suppression in optical coherence tomography angiography.

.SignificanceA long-standing challenge of the blood vessel tail artifacts along the axial direction prevents optical coherence tomography angiography (OCTA) for a comprehensive three-dimensional (3D) vascular mapping. Addressing the blood vessel tail artifacts issue will make OCTA to be a real 3D blood vessel structural imaging technique, which in combination with OCT-based blood flow velocity measurements will pave the way for a simpler and robust 3D imaging of the capillary transit time, one important parameter for the evaluation of micro circulation.ApproachWe first described the basic principles of OCTA imaging, discussed the origin of blood vessel tail artifacts in an OCTA image, then reviewed the existing OCTA techniques for tail artifacts suppression, and at last we envisioned the potential solutions for effective OCTA tail artifacts suppression.ResultsThe origin of blood vessel tail artifacts is due to the multiple scattering of photons with flowing red blood cells, which elongates the light path of the dynamic signal from vessel lumen to the tail regions. High numerical aperture implementation, subtraction-based post-data processing, Hessian filtering, and high acquisition rate-based dynamic analysis methods have been proposed to address the blood vessel tail artifacts issue in OCTA.ConclusionsHigh acquisition rate-based dynamic analysis in combination with Hessian filtering have the potential to effectively suppress the blood vessel tail artifacts and in the meantime preserve flows in small vessels within the tail region, providing real 3D OCTA imaging of blood vessel structures.

The Two-Pore Domain Potassium Channel TREK-1 Promotes Blood-Brain Barrier Breakdown and Exacerbates Neuronal Death After Focal Cerebral Ischemia in Mice.

Earlier studies have shown the neuroprotective role of TWIK-related K+ channel 1 (TREK-1) in global cerebral and spinal cord ischemia, while its function in focal cerebral ischemia has long been debated. This study used TREK-1-deficient mice to directly investigate the role of TREK-1 after focal cerebral ischemia. First, immunofluorescence assays in the mouse cerebral cortex indicated that TREK-1 expression was mostly abundant in astrocytes, neurons, and oligodendrocyte precursor cells but was low in myelinating oligodendrocytes, microglia, or endothelial cells. TREK-1 deficiency did not affect brain weight and morphology or the number of neurons, astrocytes, or microglia but did increase glial fibrillary acidic protein (GFAP) expression in astrocytes of the cerebral cortex. The anatomy of the major cerebral vasculature, number and structure of brain micro blood vessels, and blood-brain barrier integrity were unaltered. Next, mice underwent 60min of focal cerebral ischemia and 72h of reperfusion induced by the intraluminal suture method. TREK-1-deficient mice showed less neuronal death, smaller infarction size, milder blood-brain barrier (BBB) breakdown, reduced immune cell invasion, and better neurological function. Finally, the specific pharmacological inhibition of TREK-1 also decreased infarction size and improved neurological function. These results demonstrated that TREK-1 might play a detrimental rather than beneficial role in focal cerebral ischemia, and inhibition of TREK-1 would be a strategy to treat ischemic stroke in the clinic.

Analysis of Cardiovascular Disease Angiography Process Based on Rough Set and Internet of Things.

The angiography image enhancement technology has the potential to enhance the vascular structure in the image while suppressing the background and nonvascular structures simultaneously. This technology has the ability to enhance the result as close to the real structure of blood vessels as possible. Angiographic image processing is one of the essential contents in the field of medical image processing and analysis. However, the existing cardiovascular angiography schemes suffer from various issues. In this paper, the detection process of cardiovascular angiography is studied by combining the Internet of Things and rough set technology. Firstly, this paper designs the architecture design of the cardiovascular angiography process combined with the Internet of Things technology. Secondly, this paper uses a rough set algorithm to optimize the background noise and boundary shrinkage because of the sensitivity of the contrast background noise and boundary shrinkage. Simulation results verified the applicability and efficiency of the proposed model in the cardiovascular angiography scheme. The model has been optimized during implementation. Compared with the traditional algorithm, the same image data processing speed is significantly improved to ensure the enhancement effect.

Microscopic retinal blood vessels detection and segmentation using support vector machine and K-nearest neighbors.

The retina is the deepest layer of texture covering the rear of the eye, recorded by fundus images. Vessel detection and segmentation are useful in disease diagnosis. The retina's blood vessels could help diagnose maladies such as glaucoma, diabetic retinopathy, and blood pressure. A mix of supervised and unsupervised strategies exists for the detection and segmentation of blood vessels images. The tree structure of retinal blood vessels, their random area, and different thickness have caused vessel detection difficulties at machine learning calculations. Since the green band of retinal images conveys more information about the vessels, they are utilized for microscopic vessels detection. The current research proposes an administered calculation for segmentation of retinal vessels, where two upgrading stages depending on filtering and comparative histogram were applied after pre-processing and image quality improvement. At that point, statistical features of vessel tracking, maximum curvature and curvelet coefficient are extracted for each pixel. The extracted features are classified by support vector machine and the k-nearest neighbors. The morphological operators then enhance the classified image at the final stage to segment with higher accuracy. The dice coefficient is utilized for the evaluation of the proposed method. The proposed approach is concluded to be better than different strategies with a normal of 92%.

Mechanoregulation of Vascular Endothelial Growth Factor Receptor 2 in Angiogenesis.

The endothelial cells that compose the vascular system in the body display a wide range of mechanotransductive behaviors and responses to biomechanical stimuli, which act in concert to control overall blood vessel structure and function. Such mechanosensitive activities allow blood vessels to constrict, dilate, grow, or remodel as needed during development as well as normal physiological functions, and the same processes can be dysregulated in various disease states. Mechanotransduction represents cellular responses to mechanical forces, translating such factors into chemical or electrical signals which alter the activation of various cell signaling pathways. Understanding how biomechanical forces drive vascular growth in healthy and diseased tissues could create new therapeutic strategies that would either enhance or halt these processes to assist with treatments of different diseases. In the cardiovascular system, new blood vessel formation from preexisting vasculature, in a process known as angiogenesis, is driven by vascular endothelial growth factor (VEGF) binding to VEGF receptor 2 (VEGFR-2) which promotes blood vessel development. However, physical forces such as shear stress, matrix stiffness, and interstitial flow are also major drivers and effectors of angiogenesis, and new research suggests that mechanical forces may regulate VEGFR-2 phosphorylation. In fact, VEGFR-2 activation has been linked to known mechanobiological agents including ERK/MAPK, c-Src, Rho/ROCK, and YAP/TAZ. In vascular disease states, endothelial cells can be subjected to altered mechanical stimuli which affect the pathways that control angiogenesis. Both normalizing and arresting angiogenesis associated with tumor growth have been strategies for anti-cancer treatments. In the field of regenerative medicine, harnessing biomechanical regulation of angiogenesis could enhance vascularization strategies for treating a variety of cardiovascular diseases, including ischemia or permit development of novel tissue engineering scaffolds. This review will focus on the impact of VEGFR-2 mechanosignaling in endothelial cells (ECs) and its interaction with other mechanotransductive pathways, as well as presenting a discussion on the relationship between VEGFR-2 activation and biomechanical forces in the extracellular matrix (ECM) that can help treat diseases with dysfunctional vascular growth.

Combination Therapy of Placenta-Derived Mesenchymal Stem Cells with WKYMVm Promotes Hepatic Function in a Rat Model with Hepatic Disease via Vascular Remodeling.

Changes in the structure and function of blood vessels are important factors that play a primary role in regeneration of injured organs. WKYMVm has been reported as a therapeutic factor that promotes the migration and proliferation of angiogenic cells. Additionally, we previously demonstrated that placenta-derived mesenchymal stem cells (PD-MSCs) induce hepatic regeneration in hepatic failure via antifibrotic effects. Therefore, our objectives were to analyze the combination effect of PD-MSCs and WKYMVm in a rat model with bile duct ligation (BDL) and evaluate their therapeutic mechanism. To analyze the anti-fibrotic and angiogenic effects on liver regeneration, it was analyzed using ELISA, qRT-PCR, Western blot, immunofluorescence, and immunohistochemistry. Collagen accumulation was significantly decreased in PD-MSCs with the WKYMVm combination (Tx+WK) group compared with the nontransplantation (NTx) and PD-MSC-transplanted (Tx) group (p < 0.05). Furthermore, the combination of PD-MSCs with WKYMVm significantly promoted hepatic function by increasing hepatocyte proliferation and albumin as well as angiogenesis by activated FPR2 signaling (p < 0.05). The combination therapy of PD-MSCs with WKYMVm could be an efficient treatment in hepatic diseases via vascular remodeling. Therefore, the combination therapy of PD-MSCs with WKYMVm could be a new therapeutic strategy in degenerative medicine.

Sulfur Dioxide: Endogenous Generation, Biological Effects, Detection, and Therapeutic Potential.

Significance: Previously, sulfur dioxide (SO2) was recognized as an air pollutant. However, it is found to be endogenously produced in mammalian tissues. As a new gasotransmitter, SO2 is involved in regulating the structure and function of blood vessels, heart, lung, gastrointestinal tract, nervous system, etc.Recent Advances: Increasing evidence showed that endogenous SO2 regulates cardiovascular physiological processes, such as blood pressure control, vasodilation, maintenance of the normal vascular structure, and cardiac negative inotropy. Under pathological conditions including hypertension, atherosclerosis, vascular calcification, aging endothelial dysfunction, myocardial injury, myocardial hypertrophy, diabetic myocardial fibrosis, sepsis-induced cardiac dysfunction, pulmonary hypertension, acute lung injury, colitis, epilepsy-related brain injury, depression and anxiety, and addictive drug reward memory consolidation, endogenous SO2 protects against the pathological changes via different molecular mechanisms and the disturbed SO2/aspartate aminotransferase pathway is likely involved in the mechanisms for the earlier mentioned pathologic processes. Critical Issues: A comprehensive understanding of the biological effects of endogenous SO2 is extremely important for the development of novel SO2 therapy. In this review, we summarized the biological effects, mechanism of action, SO2 detection methods, and its related prodrugs. Future Directions: Further studies should be conducted to understand the effects of endogenous SO2 in various physiological and pathophysiological processes and clarify its underlying mechanisms. More efficient and accurate SO2 detection methods, as well as specific and effective SO2-releasing systems should be designed for the treatment and prevention of clinical related diseases. The translation from SO2 basic medical research to its clinical application is also worthy of further study. Antioxid. Redox Signal. 36, 256-274.

Tianma Gouteng Decoction regulates oxidative stress and inflammation in AngII-induced hypertensive mice via transcription factor EB to exert anti-hypertension effect

Hypertension is one of the important causes of cardiovascular diseases, and the imbalance of vascular homeostasis caused by oxidative stress and endothelial inflammation occurs throughout hypertension pathogenesis. Therefore, inhibiting oxidative stress and endothelial inflammation is important for treating hypertension. Tianma Gouteng Decoction (TGD) is a Chinese herbal medicine that is commonly used to treat hypertension in China, and demonstrates clinically effective antihypertensive effects. However, its blood pressure reduction mechanism remains unclear. In this study, we further determined the antihypertensive effects of TGD and revealed its underlying mechanism. We established an AngII-induced hypertension mice model, which was treated with TGD for six weeks. We monitored blood pressure, heart rate, and body weight every week. After six weeks, we detected changes in the structure and function of the heart, the structure of blood vessels, and vasomotor factors. We also detected the expression of oxidative stress and inflammation-related genes. We found that TGD can significantly reduce blood pressure, improve cardiac structure and function, and reverse vascular remodeling, which could be due to the inhibition of oxidative stress and inflammation. We also found that the effect of inhibiting oxidative stress and inflammation could be related to the up-regulation of transcription factor EB (TFEB) expression by TGD. Therefore, we used AAV9 to knock down TFEB and observe the role of TFEB in TGD's antihypertensive and cardiovascular protection properties. We found that after TFEB knockdown, the protective effect of TGD on blood pressure and cardiovascular remodeling in AngII-induced hypertensive mice was inhibited, and that it was unable to inhibit oxidative stress and inflammation. Therefore, our study demonstrated for the first time that TGD could exert anti-oxidative stress and anti-inflammatory effects through TFEB and reverse the cardiovascular remodeling caused by hypertension.

Effect of hypoxia-inducible factors in tumor infiltrating macrophage on tumor growth

Tumor blood vessel structure is different from normal blood vessel features in terms of short lumen diameter, serpentine course and poor tight junction formation. These phenomena lead to form specific tissue environment, so called tumor microenvironments (TME). The TME polarizes tumor-infiltrating macrophages towards tumor supportive phenotype. We have previously reported that prolyl-hydroxylase inhibitor (PHDi) improved blood flow, hypoxia and TME in tumor tissues. The PHDi action mechanism is PHD inhibition, resulting in increasing hypoxia-inducing factors (HIFs) expression level. But the detail of its mechanism is unclear. In this study, we investigated the effect of HIFs in tumor infiltrating macrophage on tumor growth of PHD inhibitors on tumor progression.