Vascular Endothelial Response Research Articles

Regulation of the HMGA2-SNAI2/CXCR4 axis in atherosclerosis and retinal neovascularization: new therapeutic insights.

Atherosclerosis (AS) is a vascular disease associated with endothelial damage, plaque formation, and retinal neovascularization (RNV), leading to visual impairment. Research indicates that vascular endothelial dysfunction, lipid deposition, and inflammatory responses contribute to the formation of plaques and atherosclerotic lesions. Among the common complications, studies have shown that RNV and the molecular mechanisms of AS hold significant clinical importance. In this study, we identified the overexpression of the gene heat shock protein 90 (HSP90) through transcriptome sequencing. Subsequent protein expression analysis and inhibition experiments in corresponding animal models confirmed the crucial role of HSP90 in the modulation of this disease. Research findings revealed an increase in the expression of HSP90, HMGA2, Snail family transcriptional repressor 2 gene (SNAI2), CXC chemokine receptor 4 (CXCR4), and vascular endothelial growth factor (VEGF) in atherosclerotic mouse tissues. Inhibition of HSP90 expression reduced vascular neovascularization and downregulated the expression of HMGA2 and VEGF. Given that HSP90 can promote HMGA2 expression, which, in turn, facilitates angiogenesis, we conducted lentiviral infection experiments on primary retinal endothelial cells obtained from atherosclerotic mice, confirming the regulatory role of HSP90 in modulating HMGA2 expression through the SNAI2/CXCR4 signaling pathway and its involvement in retinal endothelial neovascularization. In conclusion, our study highlights the significant regulatory role of HSP90 in AS-induced RNV, providing a new target for disease treatment. Furthermore, this research extensively explores the mechanism of HSP90 in regulating RNV and associated signaling pathways, offering novel insights and laying a solid foundation for future studies in this disease domain.

The mineralocorticoid receptor in diabetic kidney disease.

Diabetes mellitus is one of the leading causes of chronic kidney disease and its progression to end-stage kidney disease (ESKD). Diabetic kidney disease (DKD) is characterized by glomerular hypertrophy, hyperfiltration, inflammation, and the onset of albuminuria, together with a progressive reduction in glomerular filtration rate. This progression is further accompanied by tubulointerstitial inflammation and fibrosis. Factors such as genetic predisposition, epigenetic modifications, metabolic derangements, hemodynamic alterations, inflammation, and inappropriate renin-angiotensin-aldosterone system (RAAS) activity contribute to the onset and progression of DKD. In this context, decades of work have focused on glycemic and blood pressure reduction strategies, especially targeting the RAAS to slow disease progression. Although much of the work has focused on targeting angiotensin II, emerging data support that the mineralocorticoid receptor (MR) is integral in the development and progression of DKD. Molecular mechanisms linked to the underlying pathophysiological changes derived from MR activation include vascular endothelial and epithelial cell responses to oxidative stress and inflammation. These responses lead to alterations in the microcirculatory environment, the abnormal release of extracellular vesicles, gut dysbiosis, epithelial-mesenchymal transition, and kidney fibrosis. Herein, we present recent experimental and clinical evidence on the MR in DKD onset and progress along with new MR-based strategies for the treatment and prevention of DKD.

Promotes M1-polarization and diabetic wound healing using Prussian blue nanozymes

Long-term inflammation and impaired angiogenesis are the main reasons for the difficulty of diabetic wound healing. What to do to effectively promote vascular endothelial cell response and immune cell reprogramming is the key to diabetic skin healing. However, contemporary therapies cannot simultaneously coordinate the promotion of vascular endothelial cells and macrophage polarization, which leads to an increased rate of disability in patients with chronic diabetes. Therefore, we developed a method of repair composed of self-assembling Prussian blue nanoenzymes, which achieved synergistic support for the immune microenvironment, and also contributed to macrophage polarization in the tissue regeneration cycle, and enhanced vascular endothelial cell activity. The template hydrothermal synthesis PB-Zr nanoplatform was prepared and locally applied to wounds to accelerate wound healing through the synergistic effect of reactive oxygen species (ROS). PB-Zr significantly normalized the wound microenvironment, thereby inhibiting ROS production and inflammatory response, which may be because it inhibited the M1 polarization of macrophages in a rat model of wound. PB-Zr treatment significantly promoted the activity of vascular endothelial cells, which better promoted the growth and regeneration of other tissues in the body. The results confirmed the disease microenvironment of PB-Zr-mediated wound therapy and indicated its application in other inflammation-related diseases.

Vascular endothelial effects of dibutyl phthalate: In vitro and in vivo evidence

Dibutyl phthalate (DBP) is widely used in many consumer and personal care products. Here, we report vascular endothelial response to DBP in three different exposure scenarios: after short-term exposure (24 h) of human endothelial cells (ECs) EA.hy926 to 10−6, 10−5, and 10−4 M DBP, long-term exposure (12 weeks) of EA.hy926 cells to 10−9, 10−8, and 10−7 M DBP, and exposure of rats (28 and 90 days) to 100, 500, and 5000 mg DBP/kg food. We examined different vascular functions such as migration of ECs, adhesion of ECs to the extracellular matrix, tube formation, the morphology of rat aorta, as well as several signaling pathways involved in controlling endothelial function. Short-term in vitro exposure to DBP increased migration of ECs through G protein-coupled estrogen receptor, extracellular signal-regulated kinase 1/2, and nitric oxide (NO) signaling and decreased adhesion to gelatin. Long-term in vitro exposure to DBP transiently increased EC migration and had a bidirectional effect on EC adhesion to gelatin and tube formation. These effects were accompanied by a sustained increase in NO production and endothelial NO synthase (eNOS) and Akt activity. In vivo, exposure to DBP for 90 days decreased the aortic wall-to-lumen ratio and increased eNOS and Akt phosphorylation in ECs of rat aorta. This comparative investigation has shown that exposure to DBP may affect vascular function by altering EC migration, adhesion to gelatin, and tube formation after short- and long-term in vitro exposure and by decreasing the aortic wall-to-lumen ratio in vivo. The eNOS-NO and Akt signaling could be important in mediating the effects of DBP in long-term exposure scenarios.

CircLZIC regulates ox-LDL-induced HUVEC cell proliferation and apoptosis via Micro-330-5p/NOTCH2 axis in atherosclerosis.

Atherosclerosis (AS) is a major chronic non-communicable disease and a primary cause of cardiovascular disease. Recent studies have shown that circRNAs are potential epigenetic factors that regulate vascular endothelial inflammatory responses and AS progression. Therefore, identification of the circRNAs that regulate ox-LDL levels is a critical step to understanding the pathology of AS. Our study is aim to investigate how circLZIC regulates atherosclerosis (AS) via the Micro-330-5p/NOTCH2 regulatory axis. The results showed that CircLZIC and NOTCH2 are highly expressed in human AS clinical samples, while Micro-330-5p is expressed locally. The CCK-8 experiment results showed that circLZIC promotes the proliferation of HUVECS cells. Flow cytometry analysis showed that circLZIC act as an inhibitor of HUVEC cell apoptosis. The expression level of Micro-330-5p can be up-regulated by transfection of small interfering RNA against circLZIC. Further, Starbase predicted that Micro-330-5p could target and regulate NOTCH2. Next, we confirmed that overexpression of Micro-330-5p could significantly reduce the expression of fluorescein using the double Luciferase reporter assay. RIP-qRT-PCR experiment showed that Micro-330-5p and NOTCH2 mRNAs are effectively enriched by ago2 protein. Further, we found that knocking down circLZIC increases the expression of Micro-330-5p and promotes cell apoptosis, while inhibiting the expression of NOTCH2 and cell activity. On the other hand, co-transfection of Micro-330-5p inhibitor decreases Micro-330-5p expression and inhibit cell apoptosis, while increasing NOTCH2 expression and cell activity. In conclusion, CircLZIC regulates HUVEC cell activity by the Micro-330-5p/NOTCH2 signaling pathway, suggesting that circLZIC plays a key role in atherosclerosis development.

Phototuning of Hyaluronic-Acid-Based Hydrogel Properties to Control Network Formation in Human Vascular Endothelial Cells.

In vitro network formation by endothelial cells serves as a fundamental model for studies aimed at understanding angiogenesis. The morphogenesis of these cells to form a network is intricately regulated by the mechanical and biochemical properties of the extracellular matrix. Here the effects of modulating these properties in hydrogels derived from phenolated hyaluronic acid (HA-Ph) and phenolated gelatin (Gelatin-Ph) are presented. Visible-light irradiation in the presence of tris(2,2'-bipyridyl)ruthenium(II) chloride hexahydrate and sodium persulfate induces the crosslinking of these polymers, thereby forming a hydrogel and degrading HA-Ph. Human vascular endothelial cells form networks on the hydrogel prepared by visible-light irradiation for 45min (42W cm-2 at 450nm) but not on the hydrogels prepared by irradiation for 15, 30, or 60min. The irradiation time-dependent degradation of HA-Ph and the changes in the mechanical stiffness of the hydrogels, coupled with the expressions of RhoA and β-actin genes and CD44 receptors in the cells, reveal that the network formation is synergistically influenced by the hydrogel stiffness and HA-Ph degradation. These findings highlight the potential of tailoring HA-based hydrogel properties to modulate human vascular endothelial cell responses, which is critical for advancing their application in vascular tissue engineering.

방과 후 라틴댄스 활동이 비만 아동의 혈관내피세포 기능 및 혈류 반응에 미치는 영향

방과 후 라틴댄스 활동이 비만 아동의 혈관내피세포 기능 및 혈류 반응에 미치는 영향

Baculovirus-mediated endostatin and angiostatin activation of autophagy through the AMPK/AKT/mTOR pathway inhibits angiogenesis in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a highly vascularized carcinoma, and targeting its neovascularization represents an effective therapeutic approach. Our previous study demonstrated that the baculovirus-mediated endostatin and angiostatin fusion protein (BDS-hEA) effectively inhibits the angiogenesis of vascular endothelial cells and the growth of HCC tumors. However, the mechanism underlying its anti-angiogenic effect remains unclear. Increasing evidence suggests that autophagy has a significant impact on the function of vascular endothelial cells and response to cancer therapy. Hence, the objective of this research was to investigate the correlation between BDS-hEA-induced angiogenesis inhibition and autophagy, along with potential regulatory mechanisms. Our results demonstrated that BDS-hEA induced autophagy in EA.hy926 cells, as evidenced by the increasing number of autophagosomes and reactive oxygen species, accompanied by an upregulation of Beclin-1, LC3-II/LC3-I, and p62 protein expression. Suppression of autophagy using 3-methyladenine attenuated the functions of BDS-hEA-induced EA.hy926 cells, including the viability, proliferation, invasion, migration, and angiogenesis. Moreover, BDS-hEA induced autophagy by downregulating the expression of CD31, VEGF, and VEGFR2, as well as phosphorylated protein kinase B (p-AKT) and phosphorylated mammalian target of rapamycin (p-mTOR), while concurrently upregulating phosphorylated AMP-activated protein kinase (p-AMPK). The in vivo results further indicated that inhibition of autophagy by chloroquine significantly impeded the ability of BDS-hEA to suppress HCC tumor growth in mice. Mechanistically, BDS-hEA prominently facilitated autophagic apoptosis in tumor tissues and decreased the levels of ki67, CD31, VEGF, MMP-9, p-AKT, and p-mTOR while simultaneously enhancing the p-AMPK expression. In conclusion, our findings suggest that BDS-hEA induces autophagy as a cytotoxic response by modulating the AMPK/AKT/mTOR signaling pathway, thereby exerting anti-angiogenic effects against HCC.

Relationship between Serum Vascular Endothelial Growth Factor-A Levels and Response to Chemotherapy in Cervical Cancer

Introduction: cervical cancer ranks second in gynecological cancer worldwide. 62-82 % of cervical cancer patients present at an advanced stage and respond poorly to treatment. Assessment of chemotherapy response requires examination of the biomarker Vascular endothelial growth factor-A (VEGF-A), which is the main regulator of the abnormal angiogenesis process. Objectives: this study aims to analyze the relationship between serum VEGF-A levels and the response to neoadjuvant chemotherapy in cervical cancer patients. Methods: this research is Quasi-Experimental, pretest and posttest without control. Total sample: 30 stages IIIB cervical cancer patients underwent a pretest before cisplatin chemotherapy by measuring cervical lesions using ultrasound and serum VEGF-A levels using ELISA. 3 weeks after the third cycle of chemotherapy, a posttest examination is carried out like the pretest examination. Results: the results showed a significant reduction in serum VEGF-A levels and cervical lesion diameter after chemotherapy (p=0,032), (p=0,000). In response to neoadjuvant chemotherapy, 21 patients responded negatively, and 9 responded positively. High levels of VEGF-A before chemotherapy gave a negative response (p=0,042) and low levels of VEGF-A after chemotherapy gave a positive response (p=0,049). Conclusions: this study concludes that there is a relationship between high serum VEGF-A levels before chemotherapy with a negative response and low serum VEGF-A levels after chemotherapy with a positive response in cervical cancer patients

Effect of mild moxibustion at 45 ℃ with different durations at "Zusanli" （ST36） on the inflammatory factors in the abdominal aorta of hyperlipidemia rats

To investigate the effects of mild moxibustion at 45°C on the chronic inflammatory response of the abdominal aorta in rats with hyperlipidemia and the effects of different moxibustion durations. Thirty-six SD rats were randomly divided into the following groups： blank control group (2 weeks), model group (2 weeks), moxibustion group (2 weeks), blank group (4 weeks), model group (4 weeks), and moxibustion group (4 weeks). A model of hyperlipidemia with chronic inflammation was established through high-fat diet feeding for 8 weeks. Rats in the moxibustion groups received mild moxibustion treatment at bilateral "Zusanli"(ST36) at 45 °C, 10 min every time, once a day, for consecutive 2 or 4 weeks. The morphology of the abdominal aorta in each group was observed by using HE staining. Contents of serum total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), oxidized low-density lipoprotein (ox-LDL), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), endothelin-1 (ET-1) and the contents of nitric oxide (NO), ox-LDL, and ET-1 in the abdominal aorta were measured by using ELISA. Protein and mRNA expressions of IL-6 and TNF-α in the abdominal aorta of rats in each group were detected by using Western blot and real-time fluorescence quantitative PCR respectively. The positive expression of IL-6 in the abdominal aorta of rats was detected by Immunofluorescence. Compared to the blank control group, rats in the model group had increased contents of LDL, TC, TG, ox-LDL, VCAM-1, ICAM-1, IL-6, TNF-α, and ET-1 in the serum, increased contents of ox-LDL and ET-1 in the abdominal aorta, increased protein and mRNA expressions of IL-6 and TNF-α in the abdominal aorta(P<0.01, P<0.05, P<0.001), with decreased HDL content in the serum, decreased NO content in the abdominal aorta (P<0.01, P<0.05), as well as dark pink abdominal aorta, rough textures in the adventitia, media, and intima, and rough endothelial layer. Compared to the model group(2 weeks), LDL, ICAM-1, ET-1 contents in the serum, ox-LDL content in the abdominal aorta were decreased(P<0.05), while serum IL-6 and TNF-α contents, and NO content in the abdominal aorta were significantly increased(P<0.01, P<0.05), with smoother vascular walls, and relatively clear nucleus and surrounding tissue structures of abdominal aorta in the moxibustion group(2 weeks). Compared to the model group(4 weeks), contents of LDL, TC, TG, VCAM-1, ICAM-1, IL-6, TNF-α, ox-LDL, and ET-1 in the serum, ox-LDL and ET-1 contents in abdominal aorta, protein and mRNA expressions of IL-6 and TNF-α in the abdominal aorta were significantly decreased(P<0.05, P<0.01), while HDL content in the serum and NO content in the abdominal aorta were significantly increased(P<0.05, P<0.01), with smoother vascular walls, and relatively clear nucleus and surrounding tissue structures of abdominal aorta in the moxibustion group(4 weeks). In addition, content of HDL in the serum were significantly increased(P<0.05), while TNF-α content in the serum, protein expression of IL-6 in the abdominal aorta were significantly decreased (P<0.001, P<0.05), with smoother vascular walls, and clearer nucleus and surrounding tissue structures of abdominal aorta in the moxibustion group(4 weeks), in comparison with the moxibustion group(2 weeks). Mild moxibustion of 45 °C at ST36 can improve vascular endothelial damage and inflammatory response induced by high-fat diet by regulating serum lipids, vascular tone, adhesion molecules, and inflammatory factors, of which the effect of moxibustion intervention for 4 weeks is more significant.

RNA-binding protein HuR controls vascular endothelial cell inflammatory responses to tumor necrosis factor-A and is associated with atherosclerosis progression in humans

RNA-binding protein HuR controls vascular endothelial cell inflammatory responses to tumor necrosis factor-A and is associated with atherosclerosis progression in humans

Circular RNA RSU1 promotes retinal vascular dysfunction by regulating miR-345-3p/TAZ

Diabetic mellitus-induced diabetic retinopathy is a significant cause of visual impairment and blindness in adults. Circular RNAs (circRNAs) have been shown to play initial roles in vascular progression. However, the mechanism underlying diabetes mellitus-induced vascular complications remains largely unknown. In circRNA chip experiments, circRSU1 was found to be generally overexpressed in diabetic retinopathy patients. Human retina endothelial cells were stably transfected with lentiviruses carrying a circRSU1 interference plasmid. CircRSU1 downregulation alleviated diabetes mellitus induced retina vascular dysfunction, resulting in decreased vascular endothelial growth factor levels, inflammatory responses and oxidative stress. Mechanistically, we showed that elevated circRSU1 expression upregulated the TAZ levels by sponging miR-345-3p. Downregulation of TAZ reversed the vascular dysfunction that was caused by increased circRSU1 expression under hyperglycaemic conditions. In conclusion, overexpression of circRSU1 promotes vascular dysfunction by sponging miR-345-3p to increase the TAZ levels under diabetic conditions. We provide evidence that circRSU1 is a potential therapeutic target for treating diabetes mellitus-induced vascular dysfunction.

Nanoplastic-induced vascular endothelial injury and coagulation dysfunction in mice

Nanoplastics are the persistent pollutants in a variety of environments, representing a potential threat to human health. Notably, plastic particles have been detected in sample of human bloodstream. It is thus significant to investigate the effects of nanoplastics on the cardiovascular system owing to its ease transfer through the bloodstream to other organs. However, few studies have been performed to evaluate the cardiovascular toxicity of nanoplastics. Herein, we pursued to investigate the adverse cardiovascular impacts of polystyrene (PS), PS-NH2 and PS-COOH nanoplastics on mice. Experimental results demonstrated that the exposure to these nanoplastics could result in structural damage of vascular endothelial cells and inflammatory response. Moreover, it was found out that the dysfunctions of coagulation and prethrombotic state were caused by nanoplastics, which could be ascribed to the activation of JAK1/STAT3/TF signaling pathway. In summary, results clearly indicated that nanoplastic exposure lead to vascular toxicity to mice, which serves as a basis for future studies about the potential physiological threat of nanoplastics to humans.

Soybean-Derived Tripeptide Leu-Ser-Trp (LSW) Protects Human Vascular Endothelial Cells from TNFα-Induced Oxidative Stress and Inflammation via Modulating TNFα Receptors and SIRT1.

Soybean is a rich source of high-quality proteins and an excellent food source of bioactive peptides. A tripeptide, Leu-Ser-Trp (LSW), was previously identified from soybean as an angiotensin-converting enzyme inhibitory peptide. In the present work, we further studied its antioxidant and anti-inflammatory activities in human vascular endothelial cells (EA.hy926) and elucidated the mechanisms underlying these biological activities. In tumor necrosis factor alpha (TNFα)-stimulated EA.hy926 cells, LSW significantly inhibited oxidative stress, both reduced superoxide and malondialdehyde levels (p &lt; 0.001), owing to its free-radical-scavenging ability. LSW treatment also mitigated the elevated protein expression of vascular adhesion molecule-1 (p &lt; 0.001) and cyclooxygenase 2 (p &lt; 0.01) via inhibition of NF-κB and p38/JNK signaling, respectively. Additionally, LSW also inhibited the endogenous formation of TNFα and attenuated the expression of its two receptors in EA.hy926 cells. Furthermore, LSW upregulated sirtuin-1 level, which partially contributed to its anti-inflammatory activity. These results demonstrate the multiple roles of LSW in ameliorating vascular endothelial oxidative stress and inflammatory responses, which support its uses as a nutraceutical or functional food ingredient for combating endothelial dysfunction and cardiovascular diseases.

Modulation of vascular endothelial inflammatory response by proprotein convertase subtilisin-kexin type 9

Background and AimsEndotoxins carried within LDL are cleared from the circulation via hepatic LDL receptor (LDLR)-mediated endocytosis. Proprotein convertase subtilisin-kexin type 9 (PCSK9) reduces this clearance by down-regulating LDLR density on hepatocytes. In addition to hepatocytes, vascular endothelial cells also express receptor targets of PCSK9, including LDLR. Therefore, we hypothesized that PCSK9 may regulate vascular endothelial cell uptake of lipopolysaccharide (LPS) and alter the vascular endothelial cell inflammatory response. Methods and resultsWe found that LPS is internalized by human umbilical vein vascular endothelial cells (HUVECs) and LPS uptake dose-dependently increased with increasing LDL concentration. Intracellular LPS co-localized with LDL. PCSK9 and, separately, blocking antibodies against LDLR, dose-dependently decreased the vascular endothelial cell uptake of LPS and, furthermore, inhibition of endocytosis using Dynasore blocked LPS uptake. In contrast, blocking antibodies against TLR4 did not alter LPS uptake. PCSK9 decreased the LPS-induced proinflammatory response (IL-6 and IL-8 gene expression and protein secretion, and VCAM-1/ICAM-1 expression) in vascular endothelial cells. In addition, a decrease in PCSK9 and increase in LDLR, mediated by triciribine or siPCSK9, increased LPS uptake and the LPS-induced proinflammatory response. Similar results were also found in aortic vascular tissue from Pcsk9−/− mice after LPS injection. ConclusionsOur data suggest that, similar to PCSK9 treatment in hepatocytes, PCSK9 reduces vascular endothelial cell uptake of LPS via LDLR-mediated endocytosis. Consequently, PCSK9 decreases the LPS-induced proinflammatory response in vascular endothelial cells. These results raise the possibility that PCSK9 inhibition may have additional effects on vascular endothelial inflammation via this alternative pathway, beyond the known effects of PCSK9 inhibition on LDL lowering and hepatic endotoxin clearance.

Dysregulated Sulfide Metabolism in Multiple Sclerosis: Serum and Vascular Endothelial Inflammatory Responses.

Multiple sclerosis (MS) is a leading cause of neurodegenerative disability in younger individuals. When diagnosed early, MS can be managed more effectively, stabilizing clinical symptoms and delaying disease progression. The identification of specific serum biomarkers for early-stage MS could facilitate more successful treatment of this condition. Because MS is an inflammatory disease, we assessed changes in enzymes of the endothelial hydrogen sulfide (H2S) pathway in response to inflammatory cytokines. Blotting analysis was conducted to detect Cystathionine γ-lyase (CSE), Cystathionine beta synthase (CBS), and 3-mercaptopyruvate sulfurtransferase (MST) in human brain microvascular endothelial apical and basolateral microparticles (MPs) and cells following exposure to tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ). CSE was increased in MPs and cells by exposure to TNF-α/IFN-γ; CBS was elevated in apical MPs but not in cells or basolateral MPs; MST was not significantly affected by cytokine exposure. To test how our findings relate to MS patients, we evaluated levels of CSE, CBS, and MST in serum samples from healthy control and MS patients. We found significantly decreased levels of CBS and MST (p = 0.0004, 0.009) in MS serum samples, whereas serum levels of CSE were marginally increased (p = 0.06). These observations support increased CSE and lower CBS and MST expression being associated with the vascular inflammation in MS. These changes in endothelial-derived sulfide enzymes at sites of inflammation in the brain may help to explain sulfide-dependent changes in vascular dysfunction/neuroinflammation underlying MS. These findings further support the use of serum samples to assess enzymatic biomarkers derived from circulating MPs. For example, “liquid biopsy” can be an important tool for allowing early diagnosis of MS, prior to the advanced progression of neurodegeneration associated with this disease.

Astrocytes regulate vascular endothelial responses to simulated deep space radiation in a human organ-on-a-chip model.

Central nervous system (CNS) damage by galactic cosmic ray radiation is a major health risk for human deep space exploration. Simulated galactic cosmic rays or their components, especially high Z-high energy particles such as 56Fe ions, cause neurodegeneration and neuroinflammation in rodent models. CNS damage can be partially mediated by the blood-brain barrier, which regulates systemic interactions between CNS and the rest of the body. Astrocytes are major cellular regulators of blood-brain barrier permeability that also modulate neuroinflammation and neuronal health. However, astrocyte roles in regulating CNS and blood-brain barrier responses to space radiation remain little understood, especially in human tissue analogs. In this work, we used a novel high-throughput human organ-on-a-chip system to evaluate blood-brain barrier impairments and astrocyte functions 1-7 days after exposure to 600 MeV/n 56Fe particles and simplified simulated galactic cosmic rays. We show that simulated deep space radiation causes vascular permeability, oxidative stress, inflammation and delayed astrocyte activation in a pattern resembling CNS responses to brain injury. Furthermore, our results indicate that astrocytes have a dual role in regulating radiation responses: they exacerbate blood-brain barrier permeability acutely after irradiation, followed by switching to a more protective phenotype by reducing oxidative stress and pro-inflammatory cytokine and chemokine secretion during the subacute stage.

Aberrant endothelial expression of hnRNPC1/C2 and VDR and reduced maternal vitamin D levels in women with preeclampsia

Vitamin D deficiency is a widespread health problem globally and vitamin D deficiency/ insufficiency in pregnancy is a risk factor for preeclampsia, a hypertensive disorder in human pregnancy. Vitamin D elicits its biological effects through binding to its receptor VDR. In the present study, we determined maternal vascular expression of VDR and hnRNPC1/C2, a native repressor of VDR, in subcutaneous adipose tissue from women with normal pregnancy and preeclampsia. Maternal antenatal and postnatal vitamin D levels were measured. We found that hnRNPC1/C2 expression was markedly increased, while VDR expression was markedly reduced, in maternal vessel endothelium and smooth muscle cells from women with preeclampsia compared to that from normal pregnant controls. Reduced VDR expression was relevant to low maternal antenatal and postnatal vitamin D levels in women with preeclampsia.Using human umbilical vein endothelial cells (HUVECs) as an endothelial model, we further investigated the role of hnRNPC1/C2-mediated VDR expression in endothelial cells, and tested effect of hnRNPC1/C2 inhibition on endothelial response to bioactive vitamin D, 1,25(OH)2D3. Our results showed that inhibition of hnRNPC1/C2 by hnRNPC1/C2 siRNA resulted in not only an increase in endothelial VDR expression, but further improved endothelial response to 1,25(OH)2D3. These findings indicate that aberrant hnRNPC1/C2 expression may contribute to reduced vascular expression of VDR in women with preeclampsia and suggest that hnRNPC1/C2 could be a target for improving vascular endothelial cell response to vitamin D.

On the use of laser therapy in dentistry

The aim of the research: to optimize the prevention of dental complications by using electromagnetic low-intensity laser radiation (LILR) techniques on dental and periodontal tissues. Research methods. In 138 dental patients, a clinical and functional assessment of the dental apparatus was carried out, dental indices were studied, the results of vascular endothelial parameters (VEGF-A, sVEGF-R1, sVEGF-R2) and immune parameters (FNF, TNF, IFN-γ, neutrophils) of blood serum (solid-phase enzyme immunoassay with a standard set), as well as VAS pain syndrome parameters were analyzed before/after laser therapy of different wavelength, mode and range (red, infrared). Results. The study made it possible to assess the effectiveness of treatment with LILR with one wavelength and in combination of different lengths of laser radiation as independent factors of preventive exposure in dentistry patients. After applying the techniques of transcanal treatment, dental periapical tissues were treated with laser radiation, including root canals (difficult teeth roots), using the C11 attachment from the «Lazmik-01» device. The study used a modulated red spectrum of LILR in continuous and pulsed mode (l = 635 nm) and an infrared pulsed spectrum (l = 904 nm) in a continuous mode with a sequential exposure to red (l = 635 nm) pulsed and infrared continuous laser radiation (l = 904 nm). Emphasis was placed on pain syndrome, vascular endothelial and immune shifts in dental and periodontal tissues before/after using laser therapy in dental patients. Conclusion. The combination of the red spectrum of LILR in pulsed mode (l = 635 nm) with a sequential exposure to infrared laser radiation (l = 904 nm) in continuous mode provides high vascular endothelial responses in the dental and periodontal tissues of the dental apparatus, and the use of red-spectrum laser radiation in continuous mode (l = 635 nm) in dental patients provides antimicrobial and sanitizing effects, including at the level of the root canals, which is more significant than after the use of infrared laser radiation in pulsed mode, when analgesic results are higher.

Exosomal miRNA-223-3p as potential biomarkers in patients with cerebral small vessel disease cognitive impairment.

BackgroundCerebrovascular disease is a common clinical illness. Many patients with cerebrovascular disease can be accompanied by cognitive impairment. The exosomal microRNA (miRNA)-223-3p is related to vascular endothelial injury, synaptic function, inflammatory response, and other mechanisms. In this study, we investigated the levels of plasma exosomal miRNA-223-3p in patients with cerebral small vessel disease (CSVD), in order to determine whether it could be used as a more accessible potential biomarker for the early diagnosis and treatment of CSVD. This study aimed to explore whether the development of cognitive impairment can be explained by differentially expressed miRNA-223-3p by detecting the level of miRNA-223-3p, which is abundant in peripheral blood exosomes related to cognitive impairment in CSVD.MethodsThe three groups of participants included 40 patients with CSVD cognitive impairment (CSVDCI), 38 patients with CSVD, and 35 normal controls (NC). The real-time polymerase chain reaction (RT-PCR) was used to detect the expression level of blood exosomal miRNA-223-3p. In addition, we also studied the relationship between exosomal miRNA-223-3p and blood Hcy and C-reactive protein (CRP). Receiver-operating characteristic (ROC) curve analysis was used to evaluate the diagnostic efficacy of plasma exosomal miRNA-223-3p.ResultsThe expression of exosomal miRNA-223-3p in CSVD increased, and the expression of miRNA-223-3p increased significantly with the occurrence of cognitive impairment. Exosomal miRNA-223-3p was positively correlated with the expression levels of Hcy and CRP in the blood.ConclusionsThe expression of plasma exosomal miRNA-223-3p is associated with the development of cognitive impairment in patients with CSVD. It may be involved in the pathogenesis of CSVD and cognitive impairment, and can be used as a sensitive predictive biomarker.