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.

The interaction of stem cells and vascularity in peripheral nerve regeneration

The degree of nerve regeneration after peripheral nerve injury can be altered by the microenvironment at the site of injury. Stem cells and vascularity are postulated to be a part of a complex pathway that enhances peripheral nerve regeneration;however, their interaction remains unexplored. This review aims to summarize current knowledge on this interaction, including various mechanisms through which trophic factors are promoted by stem cells and angiogenesis. Angiogenesis after nerve injury is stimulated by hypoxia, mediated by vascular endothelial growth factor, resulting in the growth of preexisting vessels into new areas. Modulation of distinct signaling pathways in stem cells can promote angiogenesis by the secretion of various angiogenic factors. Simultaneously, the importance of stem cells in peripheral nerve regeneration relies on their ability to promote myelin formation and their capacity to be influenced by the microenvironment to differentiate into Schwann-like cells. Stem cells can be acquired through various sources that correlate to their differentiation potential, including embryonic stem cells, neural stem cells, and mesenchymal stem cells. Each source of stem cells serves its particular differentiation potential and properties associated with the promotion of revascularization and nerve regeneration. Exosomes are a subtype of extracellular vesicles released from cell types and play an important role in cell-to-cell communication. Exosomes hold promise for future transplantation applications, as these vesicles contain fewer membrane-bound proteins, resulting in lower immunogenicity. This review presents pre-clinical and clinical studies that focus on selecting the ideal type of stem cell and optimizing stem cell delivery methods for potential translation to clinical practice. Future studies integrating stem cell-based therapies with the promotion of angiogenesis may elucidate the synergistic pathways and ultimately enhance nerve regeneration.

Radiographic evaluation of vascularity in scaphoid nonunions:A review

Scaphoid fractures,particularly those that occur more proximally,are unreliable in achieving union due to the retrograde blood supply of the scaphoid bone.Vascular compromise is associated with the development of nonunions and avascular necrosis of the proximal pole.Due to the tenuous blood supply of the scaphoid,it is imperative that the vascularity be assessed when creating diagnostic and treatment strategies.Early detection of vascular compromise via imaging may signal impending nonunion and allow clinicians to perform interventions that aid in restoring perfusion to the scaphoid.Vascular compromise in the scaphoid presents a diagnostic challenge,in part due to the non-specific findings on plain radiographs and computed tomography.Magnetic resonance imaging techniques have dramatically improved our ability to assess the blood supply to the scaphoid and improve time to intervention.This review aims to summarize these advances and highlights the importance of imaging in assessing vascular compromise in scaphoid nonunion and in reperfusion following surgical intervention.

Correlation between Perifollicular Vascularity and Outcome in Stimulated Intrauterine Insemination Treatment Cycles: A Study Using Two-Dimensional Transvaginal Power Doppler Ultrasound

Objective:?The aim of this study is to assess any potential relationship between perifollicular vascularity and occurrence of pregnancy in cases of stimulated IUI cycles using the subjective grading system by 2D transvaginal power Doppler ultrasonography.?Design: A prospective cross sectional cohort study. Method: This is a prospective cross-sectional cohort study of 90 stimulated IUI treatment cycles. Selected women were prescribed clomiphene citrate combined with highly purified urinary follicle stimulating hormone. All patients underwent serial transvaginal ultrasound scans starting from day 6 to 7 of the cycle. Perifollicular Doppler blood flows were assessed in dominant follicles ≥18 mm. The patients then were categorized into 3 groups (high vascularity group {G3 & G4}, low vascularity group {G1 & G2} and mixed grades group). Other parameters measured included number of follicles ≥ 18 mm in both ovaries, endometrial thickness and estradiol (E2) level . Human chorionic gonadotropin (hCG) injection 10,000 IU IM was given to the patient when the dominant follicle reached 18 mm in diameter. At that time, the endometrium was evaluated as regards endometrial thickness. IUI was carried out using prepared/“washed” semen (husband). All patients received luteal support in the form of progesterone from day of IUI for 14 days. Serum Β-hCG was estimated 2 weeks after insemination. Results: In this study, from all 90 cases only 8 cases got pregnant with pregnancy rate of 8.88% (6 cases got pregnant in high grade vascularity group;2 cases in mixed grades group and no cases got pregnant?in low grade group). There was statistically significant difference among the 3 groups as regarding?the pregnancy rate (P value = 0.02). There is statistically significant difference in perifollicular resistance index (RI) and pulsatility index (PI) between pregnant and non pregnant cases (P value = 0.016 and 0.047 respectively). In this study, there is no statistically significant difference between pregnant and non pregnant cases as regarding endometrial thickness and E2 level at the day of hCG administration (P value = 0.39 and 0.76 respectively). Conclusion: Perifollicular blood-flow assessment by 2D transvaginal power Doppler is a good predictive for the outcome of stimulated IUI cycles.

Choroidal vascularity index in thyroidassociated ophthalmopathy:a crosssectional study

Background:Hemodynamic changes have been observed in patients with Graves'disease.The aim of our study was to evaluate choroidal vascular change using the choroidal vascularity index(CVi)in patients with thyroid-associated ophthalmopathy(TAO).Methods:In this cross-sectional observational study,40 patients affected by TAO were recruited.Forty healthy individuals,matched for age and sex,served as controls.Foveal enhanced-depth imaging optical coherence tomography scans were obtained from all participants.Images were binarized using the ImageJ software and luminal area(LA)and total choroidal area(TCA)were measured.CVI was calculated as the proportion of LA to TCA.The relation between CVI or subfoveal choroidal thickness(SFCT)and clinical activity score,exophthalmometric value,diplopia status,gender,and age was evaluated.Results:CVI was significantly higher in patients with TAO(P=0.004).No significant difference was observed in SFCT(P=0.200)and TCA(P=0.153)comparing TAO patients and healthy controls.LA was significantly higher in TAO group(P=0.045).On multiple regression analysis,CVI was associated with TCA(P=0.043).No association Was found between SFCT or CVI and TCA,clinical activity score,exophthalmometric value,Inami value,diplopia status,genderorage(P>0.05).Conclusions:This is the first study that has demonstrated an increase in CVI in eyes with TAO compared with healthy controls and has assessed its association with clinical features.

Pericytes protect rats and mice from sepsis-induced injuries by maintaining vascular reactivity and barrier function:implication of miRNAs and microvesicles

Background Vascular hyporeactivity and leakage are key pathophysiologic features that produce multi-organ damage upon sepsis.We hypothesized that pericytes,a group of pluripotent cells that maintain vascular integrity and tension,are protective against sepsis via regulating vascular reactivity and permeability.Methods We conducted a series of in vivo experiments using wild-type(WT),platelet-derived growth factor receptor-β(PDGFR-β)-Cre+mT/mG transgenic mice and Tie2-Cre+Cx43^(flox/flox)mice to examine the relative contribution of pericytes in sepsis,either induced by cecal ligation and puncture(CLP)or lipopolysaccharide(LPS)challenge.In a separate set of experiments with Sprague-Dawley(SD)rats,pericytes were depleted using CP-673451,a selective PDGFR-βinhibitor,at a dosage of 40 mg/(kg·d)for 7 consecutive days.Cultured pericytes,vascular endothelial cells(VECs)and vascular smooth muscle cells(VSMCs)were used for mechanistic investigations.The effects of pericytes and pericyte-derived microvesicles(PCMVs)and candidate miRNAs on vascular reactivity and barrier function were also examined.Results CLP and LPS induced severe injury/loss of pericytes,vascular hyporeactivity and leakage(P<0.05).Transplantation with exogenous pericytes protected vascular reactivity and barrier function via microvessel colonization(P<0.05).Cx43 knockout in either pericytes or VECs reduced pericyte colonization in microvessels(P<0.05).Additionally,PCMVs transferred miR-145 and miR-132 to VSMCs and VECs,respectively,exerting a protective effect on vascular reactivity and barrier function after sepsis(P<0.05).miR-145 primarily improved the contractile response of VSMCs by activating the sphingosine kinase 2(Sphk2)/sphingosine-1-phosphate receptor(S1PR)1/phosphorylation of myosin light chain 20 pathway,whereas miR-132 effectively improved the barrier function of VECs by activating the Sphk2/S1PR2/zonula occludens-1 and vascular endothelial-cadherin pathways.Conclusions Pericytes are protective against sepsis through regulating vascular reactivity and barrier function.Possible mechanisms include both direct colonization of microvasculature and secretion of PCMVs.

Ink-structing the future of vascular tissue engineering:a review of the physiological bioink design

Three-dimensional(3D)printing and bioprinting have come into view for a plannable and standardizable generation of implantable tissue-engineered constructs that can substitute native tissues and organs.These tissue-engineered structures are intended to integrate with the patient’s body.Vascular tissue engineering(TE)is relevant in TE because it supports the sustained oxygenization and nutrition of all tissue-engineered constructs.Bioinks have a specific role,representingthenecessarymedium for printability and vascular cell growth.This review aims to understand the requirements for the design of vascular bioinks.First,an in-depth analysis of vascular cell interaction with their native environment must be gained.A physiological bioink suitable for a tissue-engineered vascular graft(TEVG)must not only ensure good printability but also induce cells to behave like in a native vascular vessel,including self-regenerative and growth functions.This review describes the general structure of vascular walls with wall-specific cell and extracellular matrix(ECM)components and biomechanical properties and functions.Furthermore,the physiological role of vascular ECM components for their interaction with vascular cells and the mode of interaction is introduced.Diverse currently available or imaginable bioinks are described from physiological matrix proteins to nonphysiologically occurring but natural chemical compounds useful for vascular bioprinting.The physiological performance of these bioinks is evaluated with regard to biomechanical properties postprinting,with a view to current animal studies of 3D printed vascular structures.Finally,the main challenges for further bioink development,suitable bioink components to create a self-assembly bioink concept,and future bioprinting strategies are outlined.These concepts are discussed in terms of their suitability to be part of a TEVG with a high potential for later clinical use.

Dissolvable temporary barrier:a novel paradigm for flexible hydrogel patterning in organ-on-a-chip models

A combination of hydrogels and microfluidics allows the construction of biomimetic three-dimensional(3D)tissue models in vitro,which are also known as organ-on-a-chipmodels.The hydrogel patterningwith awell-controlled spatial distribution is typically achieved by embedding sophisticated microstructures to act as a boundary.However,these physical barriers inevitably expose cells/tissues to a less physiologically relevant microenvironment than in vivo conditions.Herein,we present a novel dissolvable temporary barrier(DTB)strategy that allows robust and flexible hydrogel patterning with great freedom of design and desirable flow stimuli for cellular hydrogels.The key aspect of this approach is the patterning of a water-soluble rigid barrier as a guiding path for the hydrogel using stencil printing technology,followed by a barrier-free medium perfusion after the dissolution of the DTB.Single and multiple tissue compartments with different geometries can be established using either straight or curved DTB structures.The effectiveness of this strategy is further validated by generating a 3D vascular network through vasculogenesis and angiogenesis using a vascularized microtumor model.As a new proof-of-concept in vasculature-on-a-chip,DTB enables seamless contact between the hydrogel and the culture medium in closed microdevices,which is an improved protocol for the fabrication ofmultiorgan chips.Therefore,we expect it to serve as a promising paradigm for organ-on-a-chip devices for the development of tumor vascularization and drug evaluation in the future preclinical studies.

In situ forming injectable MSC-loaded GelMA hydrogels combined with PD for vascularized sweat gland regeneration

Dear Editor,Three dimensional(3D)bioprinted extracellular matrix(ECM)can be used to provide both biochemical and biophysical cues to direct mesenchymal stem cells(MSCs)differentiation,and then differentiated cells were isolated for implantation in vivo using surgical procedures.However,the reduced cell activity after cell isolation from 3D constructs and low cell retention in injured sites limit its application[1].Methacrylated gelatin(GelMA)hydrogel has the advantage of fast crosslinking,which could resemble complex architectures of tissue construct in vivo[2].Here,we adopted a noninvasive bioprinting procedure to imitate the regenerative microenvironment that could simultaneously direct the sweat gland(SG)and vascular differentiation from MSCs and ultimately promote the replacement of glandular tissue in situ(Fig.1a).

Progress in the generation of spinal cord organoids over the past decade and future perspectives

Spinal cord organoids are three-dimensional tissues derived from stem cells that recapitulate the primary morphological and functional characteristics of the spinal cord in vivo.As emerging bioengineering methods have led to the optimization of cell culture protocols,spinal cord organoids technology has made remarkable advancements in the past decade.Our literature search found that current spinal cord organoids do not only dynamically simulate neural tube formation but also exhibit diverse cytoarchitecture along the dorsal-ventral and rostral-caudal axes.Moreover,fused organoids that integrate motor neurons and other regionally specific organoids exhibit intricate neural circuits that allows for functional assessment.These qualities make spinal cord organoids valuable tools for disease modeling,drug screening,and tissue regeneration.By utilizing this emergent technology,researchers have made significant progress in investigating the pathogenesis and potential therapeutic targets of spinal cord diseases.However,at present,spinal cord organoid technology remains in its infancy and has not been widely applied in translational medicine.Establishment of the next generation of spinal cord organoids will depend on good manufacturing practice standards and needs to focus on diverse cell phenotypes and electrophysiological functionality evaluation.

Advances in the differentiation of pluripotent stem cells into vascular cells

Blood vessels constitute a closed pipe system distributed throughout the body,transporting blood from the heart to other organs and delivering metabolic waste products back to the lungs and kidneys.Changes in blood vessels are related to many disorders like stroke,myocardial infarction,aneurysm,and diabetes,which are important causes of death worldwide.Translational research for new appro-aches to disease modeling and effective treatment is needed due to the huge socio-economic burden on healthcare systems.Although mice or rats have been widely used,applying data from animal studies to human-specific vascular physiology and pathology is difficult.The rise of induced pluripotent stem cells(iPSCs)provides a reliable in vitro resource for disease modeling,regenerative medicine,and drug discovery because they carry all human genetic information and have the ability to directionally differentiate into any type of human cells.This review summarizes the latest progress from the establishment of iPSCs,the strategies for differentiating iPSCs into vascular cells,and the in vivo trans-plantation of these vascular derivatives.It also introduces the application of these technologies in disease modeling,drug screening,and regenerative medicine.Additionally,the application of high-tech tools,such as omics analysis and high-throughput sequencing,in this field is reviewed.

Xuebijing improves intestinal microcirculation dysfunction in septic rats by regulating the VEGF-A/PI3K/Akt signaling pathway

BACKGROUND:This study aims to explore whether Xuebijing(XBJ) can improve intestinal microcirculation dysfunction in sepsis and its mechanism.METHODS:A rat model of sepsis was established by cecal ligation and puncture(CLP).A total of 30 male SD rats were divided into four groups:sham group,CLP group,XBJ + axitinib group,and XBJ group.XBJ was intraperitoneally injected 2 h before CLP.Hemodynamic data(blood pressure and heart rate) were recorded.The intestinal microcirculation data of the rats were analyzed via microcirculation imaging.Enzyme-linked immunosorbent assay(ELISA) kits were used to detect the serum levels of interleukin-6(IL-6),C-reactive protein(CRP),and tumor necrosis factor-α(TNF-α) in the rats.Histological analysis and transmission electron microscopy were used to analyze the injury of small intestinal microvascular endothelial cells and small intestinal mucosa in rats.The expression of vascular endothelial growth factor A(VEGF-A),phosphoinositide 3-kinase(PI3K),phosphorylated PI3K(p-PI3K),protein kinase B(Akt),and phosphorylated Akt(p-Akt) in the small intestine was analyzed via Western blotting.RESULTS:XBJ improved intestinal microcirculation dysfunction in septic rats,alleviated the injury of small intestinal microvascular endothelial cells and small intestinal mucosa,and reduced the systemic inflammatory response.Moreover,XBJ upregulated the expression of VEGF-A,p-PI3K/total PI3K,and p-Akt/total Akt in the rat small intestine.CONCLUSION:XBJ may improve intestinal microcirculation dysfunction in septic rats possibly through the VEGF-A/PI3K/Akt signaling pathway.

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.

Effect of remimazolam vs. propofol on hemodynamics during general anesthesia induction in elderly patients: Single-center, randomized controlled trial

The current study aimed to compare the effects between remimazolam and propofol on hemodynamic stability during the induction of general anesthesia in elderly patients.We used propofol at a rate of 60 mg/(kg·h)in the propofol group(group P)or remimazolam at a rate of 6 mg/(kg·h)in the remimazolam group(group R)for the induction.A processed electroencephalogram was used to determine whether the induction was successful and when to stop the infusion of the study drug.We measured when patients entered the operating room(T_(0)),when the induction was successful(T_(1)),and when before(T_(2))and 5 min after successful endotracheal intubation(T_(3)).We found that mean arterial pressure(MAP)was lower at T_(1–3),compared with T_(0) in both groups,but higher at T_(2) in the group R,whileΔMAP_(T0–T2) andΔMAP_(max) were smaller in the group R(ΔMAP_(T0–T2):the difference between MAP at time point T_(0) and T_(2),ΔMAP_(max):the difference between MAP at time point T_(0) and the lowest value from T_(0) to T_(3)).Cardiac index and stroke volume index did not differ between groups,whereas systemic vascular resistance index was higher at T_(1–3) in the group R.These findings show that remimazolam,compared with propofol,better maintains hemodynamic stability during the induction,which may be attributed to its ability to better maintain systemic vascular resistance levels.

Irrigation regimes modulate non-structural carbohydrate remobilization and improve grain filling in rice(Oryza sativa L.)by regulating starch metabolism

Recently developed ‘super’ rice cultivars with greater yield potentials often suffer from the problem of poor grain filling, especially in inferior spikelets. Here, we studied the activities of enzymes related to starch metabolism in rice stems and grains, and the microstructures related to carbohydrate accumulation and transportation to investigate the effects of different water regimes on grain filling. Two ‘super’ rice cultivars were grown under two irrigation regimes of well-watered(WW) and alternate wetting and moderate soil drying(AWMD). Compared with the WW treatment,the activities of ADP glucose pyrophosphorylase(AGPase), starch synthase(StSase) and starch branching enzyme(SBE), and the accumulation of non-structural carbohydrates(NSCs) in the stems before heading were significantly improved, and more starch granules were stored in the stems in the AWMD treatment. After heading, the activities of α-amylase, β-amylase, sucrose phosphate synthase(SPS) and sucrose synthase in the synthetic direction(SSs)were increased in the stems to promote the remobilization of NSCs for grain filling under AWMD. During grain filling, the enzymatic activities of sucrose synthase in the cleavage direction(SSc), AGPase, StSase and SBE in the inferior spikelets were increased, which promoted grain filling, especially for the inferior spikelets under AWMD.However, there were no significant differences in vascular microstructures. The grain yield and grain weight could be improved by 13.1 and 7.5%, respectively, by optimizing of the irrigation regime. We concluded that the low activities of key enzymes in carbon metabolism is the key limitation for the poor grain filling, as opposed to the vascular microstructures, and AWMD can increase the amount of NSC accumulation in the stems before heading, improve the utilization rate of NSCs after heading, and increase the grain filling, especially in the inferior spikelets, by altering the activities of key enzymes in carbon metabolism.

Impact of umbelliprenin-containing niosome nanoparticles on VEGF-A and CTGF genes expression in retinal pigment epithelium cells

AIM:To investigate the impact of niosome nanoparticles carrying umbelliprenin(UMB),an anti-angiogenic and anti-inflammatory plant compound,on the expression of vascular endothelial growth factor(VEGF-A)and connective tissue growth factor(CTGF)genes in a human retinal pigment epithelium(RPE)-like retina-derived cell line.METHODS:UMB-containing niosomes were created,optimized,and characterized.RPE-like cells were treated with free UMB and UMB-containing niosomes.The IC_(50)values of the treatments were determined using an MTT assay.Gene expression of VEGF-A and CTGF was evaluated using real-time polymerase chain reaction after RNA extraction and cDNA synthesis.Niosomes’characteristics,including drug entrapment efficiency,size,dispersion index,and zeta potential were assessed.Free UMB had an IC_(50)of 96.2μg/mL,while UMB-containing niosomes had an IC_(50)of 25μg/mL.RESULTS:Treatment with UMB-containing niosomes and free UMB resulted in a significant reduction in VEGF-A expression compared to control cells(P=0.001).Additionally,UMB-containing niosomes demonstrated a significant reduction in CTGF expression compared to control cells(P=0.05).However,there was no significant reduction in the expression of both genes in cells treated with free UMB.CONCLUSION:Both free UMB and niosome-encapsulated UMB inhibits VEGF-A and CTGF genes expression.However,the latter demonstrates significantly greater efficacy,potentially due to the lower UMB dosage and gradual delivery.These findings have implications for anti-angiogenesis therapeutic approaches targeting age-related macular degeneration.

Human pluripotent stem cell-derived kidney organoids:Current progress and challenges

Human pluripotent stem cell(hPSC)-derived kidney organoids share similarities with the fetal kidney.However,the current hPSC-derived kidney organoids have some limitations,including the inability to perform nephrogenesis and lack of a corticomedullary definition,uniform vascular system,and coordinated exit path-way for urinary filtrate.Therefore,further studies are required to produce hPSC-derived kidney organoids that accurately mimic human kidneys to facilitate research on kidney development,regeneration,disease modeling,and drug screening.In this review,we discussed recent advances in the generation of hPSC-derived kidney organoids,how these organoids contribute to the understanding of human kidney development and research in disease modeling.Additionally,the limitations,future research focus,and applications of hPSC-derived kidney organoids were highlighted.

Mufangji tang ameliorates pulmonary arterial hypertension through improving vascular remodeling,inhibiting inflammatory response and oxidative stress,and inducing apoptosis

Background:Mufangji tang(MFJT)is composed of Ramulus Cinnamomi,Radix Ginseng,Cocculus orbiculatus(Linn.)DC.,and Gypsum.In clinical settings,MFJT has been effectively employed in addressing a range of respiratory disorders,notably including pulmonary arterial hypertension(PAH).However,the mechanism of action of MFJT on PAH remains unknown.Methods:In this study,a monocrotaline-induced PAH rat model was established and treated with MFJT.The therapeutic effects of MFJT on PAH rat model were evaluated.Network pharmacology was conducted to screen the possible targets for MFJT on PAH,and the molecular docking between the main active components and the core targets was carried out.The key targets identified from network pharmacology were tested.Results:Results showed significant therapeutic effects of MFJT on PAH rat model.Analysis of network pharmacology revealed several potential targets related to apoptosis,inflammation,oxidative stress,and vascular remodeling.Molecular docking showed that the key components were well docked with the core targets.Further experimental validation results that MFJT treatment induced apoptosis(downregulated Bcl-2 levels and upregulated Bax levels in lung tissue),inhibited inflammatory response and oxdative stress(decreased the levels of IL-1β,TNF-α,inducible NOS,and malondialdehyde,and increased the levels of endothelial nitric oxide synthase,nitric oxide,glutathione and superoxide dismutase),reduced the proliferation of pulmonary arterial smooth muscle cells(downregulated ET-1 andβ-catenin levels and ERK1/2 phosphorylation,increased GSK3βlevels).Conclusion:Our study revealed MFJT treatment could alleviate PAH in rats via induction of apoptosis,inhibition of inflammation and oxidative stress,and the prevention of vascular remodeling.

Application of ultrasonography-elastography score to suspect porto-sinusoidal vascular disease in patients with portal vein thrombosis

Background:Porto-sinusoidal vascular disease(PSVD)and portal vein thrombosis(PVT)are causes of portal hypertension characterized respectively by an intrahepatic and a pre-hepatic obstacle to the flow in the portal system.As PVT may be a consequence of PSVD,in PVT patients at presentation,a pre-existing PSVD should be suspected.In these patients the identification of an underlying PSVD would have relevant implication regarding follow-up and therapeutic management,but it could be challenging.In this setting ultrasonography may be valuable in differential diagnosis.The aim of the study was to use ultrasonography to identify parameters to discriminate between PSVD and“pure”PVT and then to suspect PVT secondary to a pre-existing PSVD.Methods:Fifty-three patients with histologically proven PSVD and forty-eight patients affected by chronic PVT were enrolled and submitted to abdominal ultrasonography with elastography by acoustic radiation force impulse(ARFI).Results:ARFI was higher and superior mesenteric vein(SMV)diameter was wider in PSVD patients than in PVT patients.Thus,a prognostic score was obtained as linear combinations of the two parameters with a good discrimination capacity between PSVD and PVT(the area under the curve=0.780;95%confidence interval:0.690-0.869).Conclusions:A score based on ARFI and SMV diameter may be useful to suspect an underlying PSVD in patients with PVT and to identify a subgroup of patients to be submitted to liver biopsy.

Ascophyllum nodosum and Fucus vesiculosus ameliorate restenosis via improving inflammation and regulating the PTEN/PI3K/AKT signaling pathway

Restenosis is a common complication following coronary angioplasty.The traditional use of seaweeds for health benefits has increasingly been explored,however few studies exist reporting its protective effects on the development of restenosis and gut dysbiosis.The aim of this study was to investigate the potential of seaweed extracts(SE) of Ascophyllum nodosum and Fucus vesiculosus in inhibiting intimal hyperplasia in a rat model of restenosis and its underlying mechanisms in macrophages and vascular smooth muscle cells(vSMCs).16S rRNA sequencing was done to investigate the regulatory effect of SE on the gut microbiome of injured rats.As indicated by the results,SE significantly inhibited the progression of intimal hyperplasia in vivo,attenuated inflammation in macrophages and could inhibit the proliferation,dedifferentiation and migration of vSMCs.It was observed through immunoblotting assays that treatment with SE significantly upregulated PTEN expression in macrophages and inhibited the upregulation of PI3K and AKT expression in vSMCs.Meanwhile,according to the 16S rRNA gene sequencing analysis,supplementation with SE modulated gut microbiota composition in injured rats.In conclusion,SE could ameliorate intimal hyperplasia by inhibiting inflammation and vSMCs proliferation through the regulation of the PTEN/PI3K/AKT pathway and modulating the gut microbiome.