Expression of mucosal addressin cell adhesion molecule 1 on vascular endothelium of gastric mucosa in patients with nodular gastritis

AIM:The interaction of mucosal addressin cell adhesion molecule 1 (MAdCAM-1) with integrin α4β7 mediates lymphocyte recruitment into mucosa-associated lymphoid tissue (MALT).Nodular gastritis is characterized by a unique military pattern on endoscopy representing increased numbers of lymphoid follicles with germinal center,strongly associated with H pylori infection.The purpose of this study was to address the implication of the MAdCAM-1/integrin β7 pathway in NG. METHODS:We studied 17 patients with NG and H pylori infection and 19 H pylori-positive and 14 H pylori-negative controls.A biopsy sample was taken from the antrum and snap-frozen for immunohistochemical analysis of MAdCAM- 1 and integrin β7.In simultaneous viewing of serial sections, the percentage of MAdCAM-1-positive to von Willebrand factor-positive vessels was calculated.We also performed immunostaining with anti-CD20,CD4,CD8 and CD68 antibodies to determine the lymphocyte subsets co- expressing integrin β7. RESULTS:Vascular endothelial MAdCAM-1 expression was more enhanced in gastric mucosa with than without H pylori infection.Of note,the percentages of MAdCAM-1-positive vessels were significantly higher in the lamina propria of NG patients than in H pylori-positive controls.Strong expression of MAdCAM-1 was identified adjacent to lymphoid follicles and dense lymphoid aggregates.Integrin β7-expressing mononuclear cells,mainly composed of CD20 and CD4 lymphocytes,were associated with vessels lined with MAdCAM-1-expressing endothelium.CONCLUSION: Our results suggest that the MAdCAM一1/ integrin a4p7 homing system may participate in gastric inflammation in response to H py/o}i-infection and contributes to MALT formation, typically leading to the development of NG.

The Role of Endoplasmic Reticulum Stress-related Apoptosis in Vascular Endothelium Pathogenesis

Vascular endothelium refers to a single layer of endothelial cells that line the inner surface of blood vessels,serving as barriers and transducers between the circulating blood in the lumen and the rest of the vessel wall.Endothelial cells play essential roles in many aspects of vascular biology,such as barrier functions,thrombosis/fibrinolysis,inflammation,angiogenesis,vasoconstriction and vasodilation.

Relationship between vascular endothelium and periodontal disease in atherosclerotic lesions: Review article

Inflammation and endothelial dysfunction are linked to the pathogenesis of atherosclerotic disease. Recent studies suggest that periodontal infection and the ensuing increase in the levels of inflammatory markers may be associated with myocardial infarction, peripheral vascular disease and cerebrovascular disease. The present article aimed at reviewing contemporary data on the pathophysiology of vascular endothelium and its association with periodontitis in the scenario of cardiovascular disease.

Scutellarin Reduces Cerebral Ischemia Reperfusion Injury Involving in Vascular Endothelium Protection and PKG Signal

Flavonoid glycoside scutellarin(SCU)has been widely applied in the treatment of cerebral ischemic diseases in China.In this article,we conducted research on the working mechanisms of SCU in hypoxia reoxygenation(HR)injury of isolated cerebral basilar artery(BA)and erebral ischemia reperfusion(CIR)injury in rat models.In isolated rat BA rings,HR causes endothelial dysfunction(ED)and acetylcholine(ACh)induces endothelium-dependent vasodilation.The myography result showed that SCU(100μM)was able to significantly improve the endothelium-dependent vasodilation induced by Ach.However,SCU did not affect the ACh-induced relaxation in normal BA.Further studies suggested that SCU(10-1000μM)dose-dependently induced relaxation in isolated BA rings which were significantly blocked by the cGMP dependent protein kinase(PKG)inhibitor Rp-8-Br-cGMPs(PKGI-rp,4μM).Pre-incubation with SCU(500μM)reversed the impairment of endothelium-dependent vasodilation induced by HR,but the reversing effect was blocked if PKGI-rp(4μM)was added.The brain slice staining test in rats’model of middle cerebral artery occlusion(MCAO)induced CIR proved that the administration of SCU(45,90 mg/kg,iv)significantly reduced the area of cerebral infarction.The Western blot assay result showed that SCU(45 mg/kg,iv)increased brain PKG activity and PKG protein level after CIR surgery.In conclusion,our findings suggested that SCU possesses the ability of protecting brain cells against CIR injury through vascular endothelium protection and PKG signal.

Study on Effect of Zhixinkang Capsule(脂欣康胶囊)in TreatingUnstable Effort Angina and Hyperlipidemia and Its Function in Vascular Endothelium Protection

Objective:To observe the clinical effect and protection of vascular endothelium of Zhixin-kang Capsule (ZXKC) in middle-aged and old people with unstable effort angina and hyperlipidemia. Methods: Sixty-five patients with unstable effort angina were randomly divided into ZXKC group (34 cases) and control group (31 cases). Conventional western medical therapy was given to both groups, with ZXKC group receiving additional ZXKC treatment. Data of 20 healthy persons were taken as normal group. Forty-eight patients with hyperlipidemia were divided into ZXKC group treated with ZXKC (31 cases) and control group treated with Yixintong (17 cases). The changes of clinical symptoms and laboratory indexes in all the patients were observed before and after treatment. Results: In patients with unstable effort angina, the efficacy of treatment of ZXKC, the withdrawal rate of nitroglycerin, the relieving of symptoms, the improvement of the electrocardiogram, the counts of circulating endothelial cells, the content of platelet P-selectin, the content of plasma endothelin (ET), the activity of superoxide dismutase (SOD) and the activity of malonyldialdehyde (MDA) were all better than those in the control group. In patients with hyperlipidemia, there was no significant difference in lipids reduction between ZXKC group and the control group. In both groups, the total cholesterol (TC), triglyceride (TG), low density lipo-protein-cholesterol (LDL-C), lipoprotein(a) [Lp(a)] , ET, oxidized low density lipoprotein, MDA, arte-riosclerotic index (AI) all lowered obviously, while the SOD, HDL-C and calcitonin gene-related peptide (CGRP) were all elevated markedly. In the ZXKC group, the nitric oxide(NO) increased significantly whereas the ET/CGRP and ET/NO decreased markedly. The total effective rate in symptom relieving, the markedly effective rate, the reduction of TC, ET and ET/CGRP, and the elevation of SOD in ZXKC group were all superior to those in the control group. Conclusion: ZXKC could effectively resist myocardial ischemia, relieve angina, reduce blood lipids, protect vascular endothelial cells, inhibit the activation of platelets, and resist lipid peroxidation.

Clinical effect of Calcium Dobesilate combinated with Alprostadil in the vascular endothelium of patients with diabetic nephropathy

Objective: To research the effect of calcium dobesilate combinated with alprostadil on the changes of vascular endothelium function in patients with t diabetic nephropathy (DN), and assess the clinical effect and record the untoward effect. Method: A totoal of 120 patients with DN, then they were randomly divided into control group (n=60) and observation group(n=60). Two groups were given hypoglycemic (melbinum)+improving circulatory (calcium dobesilate), and observation group were given alprostadil on the basic, they were treated 30 days. After treatment, we observed the changes of fasting plasma glucose (FBG), 2-hour postprandial blood glucose (2hPBG), the factot of vasomotion angiokinesis (nitrogen oxide (NO), endothelin-1 (ET-1), vascular endothelial growth factor (VEGF)), diastolic function of vascular endothelium (flow mediated dilation (FMD), nitroglycerin mediated dilation (NMD)), renal function index (glomerular filtration rate (GFR), creatinine (Cr), blood urea nitrogen (BUN), albumin excrete rate (AER), urinary albumin creatinine ratio (UACR), urinary albumin evacuate ratio (UAER)), and record the untoward effect. Results: After treatment, the FBG, 2hPBG were both lower than before treatment in both groups, the difference had statistical significance (P<0.05), and the FBG, 2hPBG in the observation group were lower than the control group, and the difference had statistical significance (P<0.05). After treatment, the ET-1, VEGF were both lower than before treatment in both groups, the difference had statistical significance (P<0.05), and the ET-1, VEGF in the observation group were lower than the control group, and the difference had statistical significance (P<0.05). After treatment, the NO, FDM, NDM were higher than before treatment in both groups, the difference had statistical significance (P<0.05), and the NO, FDM, NDM in the observation group were higher than the control group, and the difference had statistical significance (P<0.05). After treatment, the GFR, Cr, BUN, AER, UACR, and UAER were both lower than before treatment in both groups, the difference had statistical significance (P<0.05), and the GFR, Cr, BUN, UACR, and UAER in the observation group were lower than the control group, and the difference had statistical significance (P<0.05). Conclusions: Treatment of the patients with DN before improving the cardiovascular system and hypoglycemic, giving the alprostadil can improve the function of vascular endothelium, rasing the clinical effect and safety.

Effects of α-lipoic acid on oxidative stress, vascular endothelium function and renal function in patients with diabetic nephropathy

Objective:To investigate the effects ofα-lipoic acid on oxidative stress, vascular endothelium function and renal function in diabetic nephropathy patients.Methods: According to random data table method, a total of 80 patients with diabetic nephropathy from September 2016 to August 2017 were divided into observation group and control group (n=40). The patients of control group were treated with routine therapy while the patients of observation group were given intravenous infusion ofα-lipoic acid on the basis of conventional therapy. The levels of oxidative stress, vascular endothelium function and renal function changes were compared between the two groups before and after the treatment.Results:The levels of SOD, MDA, NO, ET-1, RBP and CysC in the two groups before treatment were not statistically significant. Compared with the levels before treatment, the level of SOD in the observation group was significantly increased and the level of MDA was significantly decreased;the level of SOD in the observation group was significantly higher than that in the control group, and the level of MDA was significantly lower than that of the control group;the above differences were statistically significant. The levels of SOD and MDA had no significant changes in the control group before and after treatment. After treatment, the levels of ET-1, RBP and CysC in the two groups were significantly lower than those in the same group before treatment, and the observation group levels were significantly lower than those in the control group;the levels of NO in the two groups after treatment were significantly higher than those in the same group before treatment, and the observation group was significantly higher than that of the control group;the above differences were statistically significant.Conclusions: On the basis of conventional treatment, combining withα-lipoic acid can better reduce the level of oxidative stress, improve vascular endothelial function, renal function in patients with diabetic nephropathy, which has an important clinical value.

Effect of Huangqi Xiaoke Recipe combined with alprostadil on qi and yin deficiency type diabetic nephropathy and its effect on vascular endothelium and oxidative stress

Objective: To observe the clinical efficacy of Huangqi Xiaoke Decoction combined with alprostadil on qi and yin deficiency type diabetic nephropathy (DN) and its effect on vascular endothelium and oxidative stress. Methods: A total of 72 patients with qi and yin deficiency type DN who were admitted to the diabetes specialist ward and outpatient department of Baoan District Hospital of Shenzhen from January 2017 to July 2018 were enrolled. The patients were divided into the control group and the observation group according to the random number method. 36 cases in each group. Both groups were treated with conventional treatments such as hypoglycemic, hypotensive, lipid-lowering and anti-platelet aggregation. The control group was treated with alprostadil on the basis of conventional treatment. The observation group was given orally on the basis of the control group. Both groups were treated once a day for a total of 4 weeks. Compare the clinical syndrome scores and clinical efficacy of the two groups before and after treatment;fasting blood glucose (FPG), glycosylated hemoglobin (HbA1C), blood lipids (TC, TG, LDL, HDL), serum creatinine (SCr), blood urea nitrogen (BUN Endothelin-1 (ET-1), nitric oxide (NO), von Willebrand factor (vWF);glutathione peroxidase (GSH-Px), superoxide disproportionation The level of enzyme (SOD), malondialdehyde (MDA). Results:The total effective rate of TCM syndromes in observation group was 94.44%, which was significantly different from 72.22% in the control group. The scores of TCM syndromes in the observation group were significantly lower than those in the control group;Compared with the control group, the HDL-C of the observation group did not change much, there was no statistical difference;FBG, HbA1C, SCr, BUN, TC, TG, LDL-C, ET-1, vWF, MDA Significantly decreased, NO, GSH-Px, SOD increased significantly, with significant difference. Conclusion: Huangqi Xiaoke Decoction combined with alprostadil in the treatment of qi and yin deficiency type DN has significant curative effect, which can not only lower blood sugar, regulate blood lipids, improve renal function and clinical symptoms, but also inhibit oxidative stress and protect endothelial function.

Role of endothelium on the abnormal Angiotensin-mediated vascular functions in epileptic rats

Epidemiological studies have found that the risk for cardiovascular disease is increased in patients with epilepsy. The Renin Angiontensin System (RAS), an important player in vascular tone control, is also involved in many neurological disorders, including seizures and epilepsy. Although it has been reported that Angiotensin II (Ang II) release and Angiotensin receptors expression are altered in many cerebral areas in patients/animal models with neurological disorders, there are no data on the vascular function. We evaluated Ang I and Ang II-mediated vascular responses and to correlate their contractile responses to the pres- ence of endothelium and the protein levels of components of the RAS (AT1, AT2, Mas and ACE) in aorta isolated from genetically epileptic rats (WAR strain). The major finding was that the vascular contractile response induced by Ang I and Ang II is endothelium-dependent. Ang II induced contractions in aortas from Wistar rats either with intact endothelium (E+) (1.16 ± 0.04 g, n = 6) and endothelium-denuded (E-) (1.24 ± 0.04 g, n = 6). Maximum contractile response (ME) induced by Ang I was lower in Wistar E+ (0.45 ± 0.03 g, n = 6) compared with Wistar E- (1.13 ± 0.08 g, n = 6). Ang I and Ang II failed to induce contraction in WAR E+, whereas the ME induced by Ang I in WAR E- was lower (0.52 ± 0.04 g, n = 11) than in the Wistar. ME induced by Ang II in aortas from WAR was also lower (0.40 ± 0.03 g, n = 11) compared with Wistar. AT1 receptor expression in both E+ WAR and Wistar was lower than in both E- WAR and Wistar. AT2 and Mas receptor expression was higher in Wistar E- and E+ as compared to WAR E- and E+. ACE expression was higher in both E+ WAR and Wistar, but it was lower in both E- WAR and Wistar. Endothelium impairs the contractile response induced by Angiotensin in WAR, suggesting that endothelial relaxing factors play important role on the aorta contraction.

Differential diagnosis of uterine vascular anomalies:Uterine pseudoaneurysm as a cause of massive hemorrhage

In this article,we comment on the paper by Kakinuma et al published recently.We focus specifically on the diagnosis of uterine pseudoaneurysm,but we also review other uterine vascular anomalies that may be the cause of life-threating hemorrhage and the different causes of uterine pseudoaneurysms.Uterine artery pseudoaneurysm is a complication of both surgical gynecological and nontraumatic procedures.Massive hemorrhage is the consequence of the rupture of the pseudoaneurysm.Uterine artery pseudoaneurysm can develop after obstetric or gynecological procedures,being the most frequent after cesarean or vaginal deliveries,curettage and even during pregnancy.However,there are several cases described unrelated to pregnancy,such as after conization,hysteroscopic surgery or laparoscopic myomectomy.Hemorrhage is the clinical manifestation and it can be life-threatening so suspicion of this vascular lesion is essential for early diagnosis and treatment.However,there are other uterine vascular anomalies that may be the cause of severe hemorrhage,which must be taken into account in the differential diagnosis.Computed tomography angiography and embolization is supposed to be the first therapeutic option in most of them.

Understanding and controlling the variables for stromal vascular fraction therapy

In regenerative medicine,the isolation of mesenchymal stromal cells(MSCs)from the adipose tissue’s stromal vascular fraction(SVF)is a critical area of study.Our review meticulously examines the isolation process of MSCs,starting with the extraction of adipose tissue.The choice of liposuction technique,anatomical site,and immediate processing are essential to maintain cell functionality.We delve into the intricacies of enzymatic digestion,emphasizing the fine-tuning of enzyme concentrations to maximize cell yield while preventing harm.The review then outlines the filtration and centrifugation techniques necessary for isolating a purified SVF,alongside cell viability assessments like flow cytometry,which are vital for confirming the efficacy of the isolated MSCs.We discuss the advantages and drawbacks of using autologous vs allogeneic SVF sources,touching upon immunocompatibility and logistical considerations,as well as the variability inherent in donor-derived cells.Anesthesia choices,the selection between hypo-dermic needles vs liposuction cannulas,and the role of adipose tissue lysers in achieving cellular dissociation are evaluated for their impact on SVF isolation.Centrifugation protocols are also analyzed for their part in ensuring the integrity of the SVF.The necessity for standardized MSC isolation protocols is highlighted,promoting reproducibility and successful clinical application.We encourage ongoing research to deepen the understanding of MSC biology and therapeutic action,aiming to further the field of regenerative medicine.The review concludes with a call for rigorous research,interdisciplinary collaboration,and strict adherence to ethical and regulatory standards to safeguard patient safety and optimize treatment outcomes with MSCs.

Telencephalic stab wound injury induces regenerative angiogenesis and neurogenesis in zebrafish:unveiling the role of vascular endothelial growth factor signaling and microglia

After brain damage,regenerative angiogenesis and neurogenesis have been shown to occur simultaneously in mammals,suggesting a close link between these processes.However,the mechanisms by which these processes interact are not well understood.In this work,we aimed to study the correlation between angiogenesis and neurogenesis after a telencephalic stab wound injury.To this end,we used zebrafish as a relevant model of neuroplasticity and brain repair mechanisms.First,using the Tg(fli1:EGFP×mpeg1.1:mCherry)zebrafish line,which enables visualization of blood vessels and microglia respectively,we analyzed regenerative angiogenesis from 1 to 21 days post-lesion.In parallel,we monitored brain cell proliferation in neurogenic niches localized in the ventricular zone by using immunohistochemistry.We found that after brain damage,the blood vessel area and width as well as expression of the fli1 transgene and vascular endothelial growth factor(vegfaa and vegfbb)were increased.At the same time,neural stem cell proliferation was also increased,peaking between 3 and 5 days post-lesion in a manner similar to angiogenesis,along with the recruitment of microglia.Then,through pharmacological manipulation by injecting an anti-angiogenic drug(Tivozanib)or Vegf at the lesion site,we demonstrated that blocking or activating Vegf signaling modulated both angiogenic and neurogenic processes,as well as microglial recruitment.Finally,we showed that inhibition of microglia by clodronate-containing liposome injection or dexamethasone treatment impairs regenerative neurogenesis,as previously described,as well as injury-induced angiogenesis.In conclusion,we have described regenerative angiogenesis in zebrafish for the first time and have highlighted the role of inflammation in this process.In addition,we have shown that both angiogenesis and neurogenesis are involved in brain repair and that microglia and inflammation-dependent mechanisms activated by Vegf signaling are important contributors to these processes.This study paves the way for a better understanding of the effect of Vegf on microglia and for studies aimed at promoting angiogenesis to improve brain plasticity after brain injury.

The emerging role of nitric oxide in the synaptic dysfunction of vascular dementia

With an increase in global aging,the number of people affected by cerebrovascular diseases is also increasing,and the incidence of vascular dementia-closely related to cerebrovascular risk-is increasing at an epidemic rate.However,few therapeutic options exist that can markedly improve the cognitive impairment and prognosis of vascular dementia patients.Similarly in Alzheimer’s disease and other neurological disorders,synaptic dysfunction is recognized as the main reason for cognitive decline.Nitric oxide is one of the ubiquitous gaseous cellular messengers involved in multiple physiological and pathological processes of the central nervous system.Recently,nitric oxide has been implicated in regulating synaptic plasticity and plays an important role in the pathogenesis of vascular dementia.This review introduces in detail the emerging role of nitric oxide in physiological and pathological states of vascular dementia and summarizes the diverse effects of nitric oxide on different aspects of synaptic dysfunction,neuroinflammation,oxidative stress,and blood-brain barrier dysfunction that underlie the progress of vascular dementia.Additionally,we propose that targeting the nitric oxide-sGC-cGMP pathway using certain specific approaches may provide a novel therapeutic strategy for vascular dementia.

Silk-based nerve guidance conduits with macroscopic holes modulate the vascularization of regenerating rat sciatic nerve

Peripheral nerve injuries induce a severe motor and sensory deficit. Since the availability of autologous nerve transplants for nerve repair is very limited, alternative treatment strategies are sought, including the use of tubular nerve guidance conduits(tNGCs). However, the use of tNGCs results in poor functional recovery and central necrosis of the regenerating tissue, which limits their application to short nerve lesion defects(typically shorter than 3 cm). Given the importance of vascularization in nerve regeneration, we hypothesized that enabling the growth of blood vessels from the surrounding tissue into the regenerating nerve within the tNGC would help eliminate necrotic processes and lead to improved regeneration. In this study, we reported the application of macroscopic holes into the tubular walls of silk-based tNGCs and compared the various features of these improved silk^(+) tNGCs with the tubes without holes(silk^(–) tNGCs) and autologous nerve transplants in an 8-mm sciatic nerve defect in rats. Using a combination of micro-computed tomography and histological analyses, we were able to prove that the use of silk^(+) tNGCs induced the growth of blood vessels from the adjacent tissue to the intraluminal neovascular formation. A significantly higher number of blood vessels in the silk^(+) group was found compared with autologous nerve transplants and silk^(–), accompanied by improved axon regeneration at the distal coaptation point compared with the silk^(–) tNGCs at 7 weeks postoperatively. In the 15-mm(critical size) sciatic nerve defect model, we again observed a distinct ingrowth of blood vessels through the tubular walls of silk^(+) tNGCs, but without improved functional recovery at 12 weeks postoperatively. Our data proves that macroporous tNGCs increase the vascular supply of regenerating nerves and facilitate improved axonal regeneration in a short-defect model but not in a critical-size defect model. This study suggests that further optimization of the macroscopic holes silk^(+) tNGC approach containing macroscopic holes might result in improved grafting technology suitable for future clinical use.

Androgen actions on endothelium functions and cardiovascular diseases

The roles of androgens on cardiovascular physiology and pathophysiology are controversial as both beneficial and detrimental effects have been reported. Although the reasons for this discrepancy are unclear, multiple factors such as genetic and epigenetic variation, sex-specificity, hormone interactions, drug preparation and route of administration may contribute. Recently, growing evidence suggests that androgens exhibit beneficial effects on cardiovascular function though the mechanism remains to be elucidated. Endothelial cells （ECs） which line the interior surface of blood vessels are distributed throughout the circulatory system, and play a crucial role in cardiovascular function. Endothelial progenitor cells （EPCs） are considered an indispensable element for the reconstitution and maintenance of an intact endothelial layer. Endothelial dysfunction is regarded as an initiating step in development of atherosclerosis and cardiovascular diseases. The modulation of endothelial functions by androgens through either genornic or nongenomic signal pathways is one possible mechanism by which androgens act on the cardiovascular system. Obtaining insight into the mechanisms by which androgens affect EC and EPC functions will allow us to determine whether androgens possess beneficial effects on the cardiovascular system. This in turn may be critical in the prevention and therapy of cardiovascular diseases. This article seeks to review recent progress in androgen regulation of endothelial function, the sex-specificity of androgen actions, and its clinical applications in the cardiovascular system.

Effects of PAF and PAF antagonist WEB 2170 on relaxation of vascular endothelium after brief deoxygenation and reoxygenation

By means of the tension determination of rat thoracic aortic ring. it was found that PAF depressed the acetylcholine (Ach)-induced relaxation of the rings, having undergone 20 min of deoxygenation followed by 30 min of reoxygenation, to 36. 1% of norepinephine(NE) precontraction. PAF receptor antagonist WEB 2170 markedly improved the Ach-induced relaxation of the brief deoxygenated and reoxygenated rings to 86. 7 % of NE precontraction. The results indicated that PAF may be one of the mediators involved in the endothelium relaxation dysfunction related to brief deoxygenation and reoxygenation, and that PAF antagonist WEB 2170 has the protective effect on endothelium relaxation function.

RBC aggregation,deformation and adhesion to endothelium:Role of nitric oxide derived from L-Arginine and sodium nitroprusside

Red blood cells(RBCs)are the most abundant human blood cells.RBC aggregation and deformation strongly determine blood viscosity which impacts hemorheology and microcirculation.In turn,RBC properties depend on di®erent endogenous and exogenous factors.One such factor is nitric oxide(NO),which is mainly produced by endothelial cells(EC)from L-arginine amino acid in the circulatory system.Since the mechanisms of the RBC-endothelium interplay are not clear up to date and considering its possible clinical importance,the aims of this study are to investigate in vitro:(1)The effect of L-arginine induced NO on RBC aggregation and adhesion to endothelium;(2)the NO e®ect on RBC aggregation and deformation induced by L-arginine and sodium nitroprusside without the presence of endothelium in the samples.The RBC aggregation and adhesion to a monolayer of EC were studied using optical tweezers(OT).The RBC deformability and aggregation without endothelium in the samples were studied using the flow chamber method and Myrenne aggregometer.We confirmed that NO increases deformability and decreases aggregation of RBCs.We showed that the soluble guanylate cyclase pathway appears to be the only NO signaling pathway involved.In the samples with the endothelium,the "bell-shaped"dependence of RBC aggregation force on L-arginine concentration was observed,which improves our knowledge about the process of NO production by endothelium.Additionally,data related to L-arginine accumulation by endothelium were obtained:Necessity of the presence of extracellular L-arginine stated by other authors was put under question.In our study,NO decreased the RBC-endothelium adhesion,however,the tendency appeared to be weak and was not confirmed in another set of experiments.To our knowledge,this is the first attempt to measure the forces of RBC adhesion to endothelium monolayer with OT.

Efficacy of stromal vascular fraction for knee osteoarthritis:A prospective,single-centre,non-randomized study with 2 years follow-up

BACKGROUND Current osteoarthritis(OA)treatments focus on symptom relief without addressing the underlying disease process.In regenerative medicine,current treatments have limitations.In regenerative medicine,more research is needed for intra-articular stromal vascular fraction(SVF)injections in OA,including dosage optimization,long-term efficacy,safety,comparisons with other treatments,and mechanism exploration.AIM To compare the efficacy of intra-articular SVF with corticosteroid(ICS)injections in patients with primary knee OA.METHODS The study included 50 patients with Kellgren-Lawrence grades II and III OA.Patients were randomly assigned(1:1)to receive either a single intra-articular SVF injection(group A)or a single intra-articular ICS(triamcinolone)(group B)injection.Patients were followed up at 1,3,6,12,and 24 months.Visual analog score(VAS)and International Knee Documentation Committee(IKDC)scores were administered before the procedure and at all followups.The safety of SVF in terms of adverse and severe adverse events was recorded.Statistical analysis was performed with SPSS Version 26.0,IBM Corp,Chicago,IL,United States.RESULTS Both groups had similar demographics and baseline clinical characteristics.Follow-up showed minor patient loss,resulting in 23 and 24 in groups A and B respectively.Group A experienced a notable reduction in pain,with VAS scores decreasing from 7.7 to 2.4 over 24 months,compared to a minor reduction from 7.8 to 6.2 in Group B.This difference in pain reduction in group A was statistically significant from the third month onwards.Additionally,Group A showed significant improvements in knee functionality,with IKDC scores rising from 33.4 to 83.10,whereas Group B saw a modest increase from 36.7 to 45.16.The improvement in Group A was statistically significant from 6 months and maintained through 24 months.CONCLUSION Our study demonstrated that intra-articular administration of SVF can lead to reduced pain and improved knee function in patients with primary knee OA.More adequately powered,multi-center,double-blinded,randomised clinical trials with longer follow-ups are needed to further establish safety and justify its clinical use.

Three-dimensional choroidal vascularity index and choroidal thickness in fellow eyes of acute and chronic primary angle-closure using swept-source optical coherence tomography

AIM:To compare the three-dimensional choroidal vascularity index(CVI)and choroidal thickness between fellow eyes of acute primary angle-closure(F-APAC)and chronic primary angle-closure glaucoma(F-CPACG)and the eyes of normal controls.METHODS:This study included 37 patients with unilateral APAC,37 with asymmetric CPACG without prior treatment,and 36 healthy participants.Using swept-source optical coherence tomography(SS-OCT),the macular and peripapillary choroidal thickness and three-dimensional CVI were measured and compared globally and sectorally.Pearson’s correlation analysis and multivariate regression models were used to evaluate choroidal thickness or CVI with related factors.RESULTS:The mean subfoveal CVIs were 0.35±0.10,0.33±0.09,and 0.29±0.04,and the mean subfoveal choroidal thickness were 315.62±52.92,306.22±59.29,and 262.69±45.55μm in the F-APAC,F-CPACG,and normal groups,respectively.All macular sectors showed significantly higher CVIs and choroidal thickness in the F-APAC and F-CPACG eyes than in the normal eyes(P<0.05),while there were no significant differences between the F-APAC and F-CPACG eyes.In the peripapillary region,the mean overall CVIs were 0.21±0.08,0.20±0.08,and 0.19±0.05,and the mean overall choroidal thickness were 180.45±54.18,174.82±50.67,and 176.18±37.94μm in the F-APAC,F-CPACG,and normal groups,respectively.There were no significant differences between any of the two groups in all peripapillary sectors.Younger age,shorter axial length,and the F-APAC or F-CPACG diagnosis were significantly associated with higher subfoveal CVI and thicker subfoveal choroidal thickness(P<0.05).CONCLUSION:The fellow eyes of unilateral APAC or asymmetric CPACG have higher macular CVI and choroidal thickness than those of the normal controls.Neither CVI nor choroidal thickness can distinguish between eyes predisposed to APAC or CPACG.A thicker choroid with a higher vascular volume may play a role in the pathogenesis of primary angle-closure glaucoma.

Schnurri-3 inhibition rescues skeletal fragility and vascular skeletal stem cell niche pathology in the OIM model of osteogenesis imperfecta

Osteogenesis imperfecta(OI)is a disorder of low bone mass and increased fracture risk due to a range of genetic variants that prominently include mutations in genes encoding typeⅠcollagen.While it is well known that OI reflects defects in the activity of bone-forming osteoblasts,it is currently unclear whether OI also reflects defects in the many other cell types comprising bone,including defects in skeletal vascular endothelium or the skeletal stem cell populations that give rise to osteoblasts and whether correcting these broader defects could have therapeutic utility.