Fluid Shear Research Articles

Controversy in mechanotransduction - the role of endothelial cell-cell junctions in fluid shear stress sensing.

Fluid shear stress (FSS) from blood flow, sensed by the vascular endothelial cells (ECs) that line all blood vessels, regulates vascular development during embryogenesis, controls adult vascular physiology and determines the location of atherosclerotic plaque formation. Although a number of papers have reported a crucial role for cell-cell adhesions or adhesion receptors in these processes, a recent publication has challenged this paradigm, presenting evidence that ECs can very rapidly align in fluid flow as single cells without cell-cell contacts. To address this controversy, four independent laboratories assessed EC alignment in fluid flow across a range of EC cell types. These studies demonstrate a strict requirement for cell-cell contact in shear stress sensing over timescales consistent with previous literature and inconsistent with the newly published data.

In silico investigation of the reliable models of drug delivery from blood vessels to tumor using tumor spheroid-on-chip models

Due to the limitations of two-dimensional models in mimicking intratumoral drug delivery, three-dimensional tumor spheroid-on-chip models have been considered recently. Even though various models have been proposed in this field, many unknowns still exist about their reliability in imitating in vivo conditions. In addition, most of these models neglect the replication of drug transport from the bloodstream. In the current research, considering the interface of tumor and blood vessels, new designs of microfluidic devices are developed to resemble the in vivo conditions more closely. Then, drug transport in the proposed models is studied numerically using porous media theory under dynamic conditions. The simulation results of drug concentration, cell viability, fluid shear stress, and pressure distributions are compared with those of a solid tumor. As the results demonstrate, our proposed models can well mimic the in vivo conditions, including drug delivery through blood vessels. Therefore, in addition to developing tumor spheroid-on-chip models resembling tumor-vessel interaction, the present study provides a strong strategy to evaluate the reliability of in vitro models in replicating intratumoral drug delivery.

H(div)-conforming and discontinuous Galerkin approach for Herschel–Bulkley flow with density-dependent viscosity and yield stress

This paper presents a comprehensive study on Herschel–Bulkley flow, where the flow parameters are dependent on the density. The Herschel–Bulkley model is a generalized power-law model used to simulate viscoplastic fluids defined by a plasticity threshold. We consider the case where the plasticity threshold and the viscosity depend on the shear rate and fluid density. To analyze this model, we use a Huber regularization of the stress and propose an H(div)-conforming and discontinuous Galerkin (DG) numerical approximation for the coupled equations governing the flow. We discuss the stability and existence of discrete solutions and propose a semismooth Newton linearization for the numerical solution of the discretized system. Our numerical scheme is validated through several experiments that explore the behavior of Herschel–Bulkley flow under different conditions. The results demonstrate the robustness of our numerical method.

PpIX-enabled fluorescence-based detection and photodynamic priming of platinum-resistant ovarian cancer cells under fluid shear stress.

Over 75% percent of ovarian cancer patients are diagnosed with advanced-stage disease characterized by unresectable intraperitoneal dissemination and the presence of ascites, or excessive fluid build-up within the abdomen. Conventional treatments include cytoreductive surgery followed by multi-line platinum and taxane chemotherapy regimens. Despite an initial response to treatment, over 75% of patients with advanced-stage ovarian cancer will relapse and succumb to platinum-resistant disease. Recent evidence suggests that fluid shear stress (FSS), which results from the movement of fluid such as ascites, induces epithelial-to-mesenchymal transition and confers resistance to carboplatin in ovarian cancer cells. This study demonstrates, for the first time, that FSS-induced platinum resistance correlates with increased cellular protoporphyrin IX (PpIX), the penultimate downstream product of heme biosynthesis, the production of which can be enhanced using the clinically approved pro-drug aminolevulinic acid (ALA). These data suggest that, with further investigation, PpIX could serve as a fluorescence-based biomarker of FSS-induced platinum resistance. Additionally, this study investigates the efficacy of PpIX-enabled photodynamic therapy (PDT) and the secretion of extracellular vesicles under static and FSS conditions in Caov-3 and NIH:OVCAR-3 cells, two representative cell lines for high-grade serous ovarian carcinoma (HGSOC), the most lethal form of the disease. FSS induces resistance to ALA-PpIX-mediated PDT, along with a significant increase in the number of EVs. Finally, the ability of PpIX-mediated photodynamic priming (PDP) to enhance carboplatin efficacy under FSS conditions is quantified. These preliminary findings in monolayer cultures necessitate additional studies to determine the feasibility of PpIX as a fluorescence-based indicator, and mediator of PDP, to target chemoresistance in the context of FSS.

Influence of micromixing and shear on precipitation process in the jet-flow high shear reactors

Micromixing and fluid shear stress significantly affect the nucleation and growth of crystals during the precipitation process. The jet-flow high shear reactor (JFHSR) has strong shear rate and high localized energy dissipation rate, making it promising for applications where the size and the morphology of crystals need to be modified. In this paper, the micromixing properties of JFHSR were first investigated using Villermaux/Dushman method, and the intrinsic correlation among micromixing, shear, and BaSO4 crystals was explored. The results show that the stator, the increased Re and θ, the reduced feed tube diameter and the closer the feed position to the rotor promote micromixing. Excellent micromixing promotes burst nucleation by generating uniform supersaturation, while shear is more likely to provide an environment dominated by the secondary nucleation of fluid shear stress. The correlations of XS, tm (about 10−4 s) and d43,P are obtained, providing guidelines for JFHSR design and application

Suturing of the Archean Bastar craton with the Eastern Ghats Province to form the Greater Indian Landmass: Insights from geochemistry, U-Pb geochronology and phase equilibria modelling

The contact between the Archean Bastar craton (BC) and Proterozoic Eastern Ghats Province (EGP), central India, is marked by a suture zone termed Terrane Boundary Shear Zone (TBSZ). BC in this area is largely composed of hornblende-biotite granite with some mafic dykes. Rocks in the TBSZ include quartzofeldspathic (leptynite) gneiss, garnet-orthopyroxene-bearing granitoid, mafic granulites (Group A of cratonic affinity, and Group B of EGP affinity), Mg-Al granulite and an isolated exposure of orthopyroxene-bearing gneiss. Detailed geochemical analysis shows remarkable similarity between Hbl-Bt granite and Grt-Opx-bearing granitoid, with A-type affinity, and between mafic dykes and Group A mafic granulites. However, the Opx-bearing gneiss is geochemically distinct having I-type affinity, similar to TTG gneisses described from BC. Metamorphic phase equilibria analysis and trace element modelling shows that (i) melting of Opx-bearing gneiss would produce a ferroan granitic melt resembling the Hbl-Bt granite, (ii) metamorphism at appropriate P-T conditions would convert the granite to Grt-Opx-bearing granitoid and the mafic dyke to Group A mafic granulite. U-Pb geochronology of zircon constrains emplacement ages of the magmatic precursors of Opx-bearing gneiss and Grt-Opx-bearing granitoid as ca. 2.73 and ca. 2.5 Ga, respectively. These rocks were subjected to an early granulite facies metamorphism, followed by an amphibolite facies metamorphism, shearing and hydrous fluid flux. Geochronological data shows that the latter event took place at ca. 0.52 Ga, while the earlier granulite facies event can only be tentatively suggested to be of late Stenian/Tonian age. Collating all the evidence (including published geophysical and geochronological data), we suggest that the initial collision between BC and EGP took place during late Stenian/Tonian time as a consequence of formation of the Greater Indian Landmass, a part of Rodinia supercontinent. The TBSZ, probably initiated due to the late Stenian/Tonian collision, was reactivated and reworked tectonothermally at ca. 0.52 Ga, caused by far field stress effect of the Kuunga orogeny, which was strong enough to obliterate most of the imprints of the late Stenian/Tonian orogeny.

Effects of fluid shear stress on oral biofilm formation and composition and the transcriptional response of Streptococcus gordonii.

Biofilms are subjected to many environmental pressures that can influence community structure and physiology. In the oral cavity, and many other environments, biofilms are exposed to forces generated by fluid flow; however, our understanding of how oral biofilms respond to these forces remains limited. In this study, we developed a linear rocker model of fluid flow to study the impact of shear forces on Streptococcus gordonii and dental plaque-derived multispecies biofilms. We observed that as shear forces increased, S. gordonii biofilm biomass decreased. Reduced biomass was largely independent of overall bacterial growth. Transcriptome analysis of S. gordonii biofilms exposed to moderate levels of shear stress uncovered numerous genes with differential expression under shear. We also evaluated an ex vivo plaque biofilm exposed to fluid shear forces. Like S. gordonii, the plaque biofilm displayed decreased biomass as shear forces increased. Examination of plaque community composition revealed decreased diversity and compositional changes in the plaque biofilm exposed to shear. These studies help to elucidate the impact of fluid shear on oral bacteria and may be extended to other bacterial biofilm systems.

Effect of biofilm physical characteristics on their susceptibility to antibiotics: impacts of low-frequency ultrasound

Biofilms are highly resistant to antimicrobials, often causing chronic infections. Combining antimicrobials with low-frequency ultrasound (LFU) enhances antimicrobial efficiency, but little is known about the underlying mechanisms. Biofilm physical characteristics, which depend on factors such as growth conditions and age, can have significant effects on inactivation efficiency. In this study, we investigated the susceptibility of Pseudomonas aeruginosa biofilms to tobramycin, with and without LFU treatment. The biofilms were grown under low and high fluid shear to provide different characteristics. Low-shear biofilms exhibited greater thickness, roughness, and porosity and lower density, compared to high-shear biofilms. The biofilm matrix of the high-shear biofilms had a three times higher protein-to-polysaccharide ratio, suggesting greater biofilm stiffness. This was supported by microrheology measurements of biofilm creep compliance. For the low-shear biofilms without LFU, the viability of the biofilms in their inner regions was largely unaffected by the antibiotic after a 2-hour treatment. However, when tobramycin was combined with LFU, the inactivation for the entire biofilm increased to 80% after 2 h. For the high-shear biofilms without LFU, higher LFU intensities were needed to achieve similar inactivation results. Microrheology measurements revealed that changes in biofilm inactivation profiles were closely related to changes in biofilm mechanical properties. Modeling suggests that LFU changes antibiotic diffusivity within the biofilm, probably due to a “decohesion” effect. Overall, this research suggests that biofilm physical characteristics (e.g., compliance, morphology) are linked to antimicrobial efficiency. LFU weakens the biofilm while increasing its diffusivity for antibiotics.

Microbiology of human spaceflight: microbial responses to mechanical forces that impact health and habitat sustainability.

SUMMARYUnderstanding the dynamic adaptive plasticity of microorganisms has been advanced by studying their responses to extreme environments. Spaceflight research platforms provide a unique opportunity to study microbial characteristics in new extreme adaptational modes, including sustained exposure to reduced forces of gravity and associated low fluid shear force conditions. Under these conditions, unexpected microbial responses occur, including alterations in virulence, antibiotic and stress resistance, biofilm formation, metabolism, motility, and gene expression, which are not observed using conventional experimental approaches. Here, we review biological and physical mechanisms that regulate microbial responses to spaceflight and spaceflight analog environments from both the microbe and host-microbe perspective that are relevant to human health and habitat sustainability. We highlight instrumentation and technology used in spaceflight microbiology experiments, their limitations, and advances necessary to enable next-generation research. As spaceflight experiments are relatively rare, we discuss ground-based analogs that mimic aspects of microbial responses to reduced gravity in spaceflight, including those that reduce mechanical forces of fluid flow over cell surfaces which also simulate conditions encountered by microorganisms during their terrestrial lifecycles. As spaceflight mission durations increase with traditional astronauts and commercial space programs send civilian crews with underlying health conditions, microorganisms will continue to play increasingly critical roles in health and habitat sustainability, thus defining a new dimension of occupational health. The ability of microorganisms to adapt, survive, and evolve in the spaceflight environment is important for future human space endeavors and provides opportunities for innovative biological and technological advances to benefit life on Earth.

Определение вязкости и диэлектрической проницаемости жидкости методом эквивалентных схем с помощью резонатора с поперечным электрическим полем

The paper presents a method for determining the viscosity and permittivity of a liquid using the equivalent circuit method. The parameters of the Mason equivalent circuit were found for a piezoelectric resonator with a lateral electric field made of PZT-19 ceramics. The frequency dependences of the real and imaginary parts of the electrical impedance of a resonator loaded with liquid samples with different viscosity and permittivity were measured. The fitting of the theoretical frequency dependences of the real and imaginary parts of the electrical impedance of a resonator loaded with mixtures of “water - isopropyl alcohol” and “water - glycerin” to the measured dependences was carried out. As the result the dependence of the permittivity of the liquid on the additional capacitance (determined from the Mason scheme) and the dependence of the shear fluid viscosity on the imaginary part of the mechanical impedance of the fluid load (determined from the Mason scheme) were built. These dependences can be used as calibration curves to determine dielectric constant and viscosity.

Emergence of lobed wakes during the sedimentation of spheres in viscoelastic fluids

The motion of rigid particles in complex fluids is ubiquitous in natural and industrial processes. The most popular toy model for understanding the physics of such systems is the settling of a solid sphere in a viscoelastic fluid. There is general agreement that an elastic wake develops downstream of the sphere, causing the breakage of fore-and-aft symmetry, while the flow remains axisymmetric, independent of fluid viscoelasticity and flow conditions. Using a continuum mechanics model, we reveal that axisymmetry holds only for weak viscoelastic flows. Beyond a critical value of the settling velocity, steady, non-axisymmetric disturbances develop peripherally of the rear pole of the sphere, giving rise to a four-lobed fingering instability. The transition from axisymmetric to non-axisymmetric flow fields is characterized by a regular bifurcation and depends solely on the interplay between shear and extensional properties of the viscoelastic fluid under different flow regimes. At higher settling velocities, each lobe tip is split into two new lobes, resembling fractal fingering in interfacial flows. For the first time, we capture an elastic fingering instability under steady-state conditions, and provide the missing information for understanding and predicting such instabilities in the response of viscoelastic fluids and soft media.

Clinical Significance of MicroRNA-299-3p in Coronary Artery Disease Based on Bioinformatics Analysis.

The purpose of the research was to evaluate the diagnostic performance of microRNA-299-3p (miR-299-3p) in patients with coronary artery disease (CAD). The relative abundance of miR-299-3p in patients with CAD was verified by quantitative real time polymerase chain reaction (qRT-PCR) assay. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used for analysis, and target genes were predicted and enriched by DAVID software. The protein-protein interaction (PPI) network was drawn by STRING database. Receiver operating characteristic (ROC) was adopted to appraise the diagnostic value of miR-299-3p in CAD. Bioinformatics analysis showed that the GO function of miR-299-3p target genes of miR-299-3p mainly focuses on specific granular membrane, regulation of apoptotic signaling pathway, growth factor binding and so on. KEGG analysis showed that the most abundant pathways involve fluid shear stress and atherosclerosis, as well as Notch signaling pathways. PPI network showed the seven predictive genes encoding the proteins play pivotal roles in maintaining the stability and interaction of the network, especially matrix metallopeptidase 2 (MMP2) and intercellular cell adhesion molecule-1 (ICAM1). Compared with the control group, serum miR-299-3p in the CAD group was distinctly up-regulated via qRT-PCR (p < 0.001). ROC analysis showed that miR-299-3p was an important index for detecting CAD patients and major adverse cardiovascular events (MACE) patients with an AUC of 0.931 and 0.758, respectively. MiR-299-3p is involved in the development of CAD, and might become a potential biomarker for monitoring CAD.

Investigation of the dynamic and thermal performance of kinetic-static mixers: a numerical simulation study

In this paper, a numerical simulation was carried out to investigate the dynamic and thermal behaviors of various shapes of a kinetic static mixer. Three-dimensional model of the static mixer was designed using commercial Computational Fluid Dynamics (CFD) software, CFX 18.2. To examine the mixer's performance, five parameters have been considered including Re, Shear stress rate, Nu, fluid temperature and pressure drop. The fluid velocity was characterized by Reynolds numbers varying from 10 to 100, pressure drop, and shear rate has been considered for evaluating dynamic performance. Furthermore, fluid temperature and the Nusselt number was examinate to gain insights into thermal characteristics. In this study, the effectiveness of four different mixer shapes was evaluated. The outcomes underlined the significant impact changes in mixing geometry can have on the fluid's dynamic behavior, which in turn affects thermal performance. Notably, among the suggested mixer shapes, case three shows best mixing performance. This study offers significant knowledge about the dynamic and thermal behavior of kinetic static mixers, emphasizing the critical function of shape in raising overall performance.

Arrangement into layers and mechanobiology of multi-cell co-culture models of the uterine wall.

Can a co-culture of three cell types mimic the in vivo layers of the uterine wall? Three protocols tested for co-culture of endometrial epithelial cells (EEC), endometrial stromal cells (ESC), and myometrial smooth muscle cells (MSMC) led to formation of the distinct layers that are characteristic of the structure of the uterine wall in vivo. We previously showed that a layer-by-layer co-culture of EEC and MSMC responded to peristaltic wall shear stresses (WSS) by increasing the polymerization of F-actin in both layers. Other studies showed that WSS induced significant cellular alterations in epithelial and endothelial cells. Human EEC and ESC cell lines and primary MSMC were co-cultured on a collagen-coated synthetic membrane in custom-designed wells. The co-culture model, created by seeding a mixture of all cells at once, was exposed to steady WSS of 0.5 dyne/cm2 for 10 and 30 min. The co-culture of the three different cells was seeded either layer-by-layer or as a mixture of all cells at once. Validation of the models was by specific immunofluorescence staining and confocal microscopy. Alterations of the cytoskeletal F-actin in response to WSS were analyzed from the 2-dimensional confocal images through the Z-stacks following a previously published algorithm. We generated three multi-cell in vitro models of the uterine wall with distinct layers of EEC, ESC, and MSMC that mimic the in vivo morphology. Exposure of the mixed seeding model to WSS induced increased polymerization of F-actin in all the three layers relative to the unexposed controls. Moreover, the increased polymerization of F-actin was higher (P-value < 0.05) when the length of exposure was increased from 10 to 30 min. Furthermore, the inner layers of ESC and MSMC, which are not in direct contact with the applied shearing fluid, also increased their F-actin polymerization. N/A. The mixed seeding co-culture model was exposed to steady WSS of one magnitude, whereas the uterus is a dynamic organ with intra-uterine peristaltic fluid motions that vary in vivo with different time-dependent magnitude. Further in vitro studies may explore the response to peristaltic WSS or other physical and/or hormonal perturbations that may mimic the spectrum of pathophysiological aspects. Numerous in vitro models were developed in order to mimic the human endometrium and endometrium-myometrium interface (EMI) region. The present co-culture models seem to be the first constructed from EEC, ESC, and MSMC on a collagen-coated synthetic membrane. These multi-cell in vitro models better represent the complex in vivo anatomy of the EMI region. The mixed seeding multi-cell in vitro model may easily be implemented in controlled studies of uterine function in reproduction and the pathogenesis of diseases. This study was supported in part by Tel Aviv University funds. All authors declare no conflict of interest.

Effect of turbulence intensity on bubble-particle detachment mechanism in a confined vortex

Bubble-particle detachment induced by turbulence is the primary factor for the low recovery of coarse particles, which has attracted much attention in recent years. The prevailing centrifugal detachment theory has achieved broad consensus. However, due to the complexity of bubble-particle aggregate motion in the turbulent field, the influence of turbulence intensity on bubble-particle detachment mechanism remains unclear. In this study, a controlled rotating vortex was generated using a custom-made fluid channel to systematically investigate the effect of turbulence intensity on bubble-particle centrifugal detachment. Firstly, detachment behaviours of bubble-particle aggregates were captured using high-speed cameras, followed by flow field visualization of bubble-particle detachment processes using Computational Fluid Dynamics (CFD). Experimental results reveal three typical detachment modes of bubble-particle aggregates in the confined vortex: fluid shear, bubble oscillation, and particle centrifugal motion, with particle centrifugal detachment becoming dominant with increasing turbulence intensity. This shift is attributed to changes in turbulence intensity directly affecting the trajectories of bubble/aggregates and indirectly influencing the detachment mode of bubble-particle. Compared to low turbulence intensity, bubble-particle aggregates exhibit smaller rotational radii under high turbulence intensity, reducing the probability of fluid shear and bubble oscillation detachment by mitigating the influence of high-speed shear zones at the top of the cavity. Conversely, particles located at the edge of aggregates are more susceptible to acceleration by sidewall flow fields, favouring detachment through particle centrifugal motion. Moreover, unlike traditional centrifugal detachment theories, particles do not merely undergo independent circumferential motion on the bubble surface but participate as a whole with bubbles in centrifugal motion governed by vortices. These findings are expected to provide fundamental insights into the bubble-particle detachment mechanism in turbulent fields.

Discovery of delayed gas production after implantation of a continuous-flow left ventricular assist device and a preliminary exploration of the mechanisms of its occurrence.

To characterize the gas production phenomenon in the animal model of left ventricular assist device (LVAD), and study its mechanism. An in vitro bubble precipitation experiment was conducted, and the blood samples of Parma spp. animals were divided into ordinary group and oxygen-enriched group according to whether they were oxygenated or not at the time of blood collection, and a static control group was set up respectively. Blood gases were drawn and analyzed before and after the experiment. Activate the pump, and the number of air bubbles in the loop was measured by ultrasound at different rotational speeds; CFD was applied to simulate the flow field in the blood pump, and pressure, fluid velocity vector and shear force diagrams were plotted, and a thrombus model was constructed and the flow field was simulated and plotted as a cloud diagram. There was a statistical difference in the number of bubbles in the inflow and outflow tubes of the blood pump (P values of 0.04 and 0.023, respectively), and the number of bubbles in the outflow tubes of both groups was significantly higher than the number of bubbles in the inflow tubes. The number of bubbles in the tubes of both the oxygen-enriched and normal groups was significantly higher than that in the inflow group. In both the normal and oxygen-enriched groups, more gas was produced at higher speeds than at lower speeds. Blood gas analysis showed that the reduced gas composition in the blood was mainly oxygen. Flow field simulation results: the high rotation speed group had lower central pressure and greater scalar shear. The thrombus simulation group was more prone to turbulence, sudden pressure changes, and greater shear than the normal group. Blood gas production is associated with higher partial pressures of blood oxygen, higher rotation speed, and intrapump thrombosis, and the mechanism of pump gas production is degassing of dissolved gases rather than cavitation of water, and the gas released is most likely to have oxygen. The degassing phenomenon is an warning factor for pump thrombosis.

Effect of fluid scour on stress distribution of film-substrate system

Under strong fluid scour in special service environment, the film-substrate system is prone to weaken its mechanical properties due to the additional shear stress by fluid, resulting in film debonding. The present study establishes a mechanical model incorporating the fluid shear stress for a film-substrate system with partial debonding. The debonding length, scour strength and thermal mismatch are considered in the model, respectively. Fluid induces compressive stress on inflow side and tensile stress on outflow side. Potential debonding behavior of film by the additional shear stress is qualitatively analyzed. Results show that the compressive stress by fluid releases part of the tensile stress of thermal mismatch, may mitigate surface cracking of film. The surface scour effect is amplified by the partial debonding, and is further enhanced with the increase of debonding length. The unevenness of stress distribution at the interface is intensified by the debonding and fluid scouring. The fluid scour poses a potential threat to the film-substrate system.

Study On the Mechanism of Action of Qili Qiangxin Capsule in the Treatment of Heart Failure Based on Network Pharmacology and Molecular Docking Method

Objective: To investigate the pharmacodynamic substances and mechanism of action of Qili Qiangxin Capsule in the treatment of heart failure based on network pharmacology and molecular docking technology. Methods: The active ingredients and drug targets of Qili Qiangxin Capsule were obtained from databases such as TCMSP, GeneCards, OMIM, PharmGkb, TTD, and DrugBank databases were searched for heart failure disease targets. The drug targets and disease targets were corrected by the UniProt database, then the Venn diagram was drawn, and the intersecting genes were screened. Cytoscape 3.8.0 software was used to draw the active ingredient-disease target network for topological analysis. PPI network was constructed in the STRING database platform to predict the core targets. Bioconductor package was used to perform KEGG pathway analysis. autoDock Vina software was used to molecularly dock the core targets with the main active ingredients, and Pymol software visualised the results. Results: Screening of 209 active ingredients of Qili Qiangxin Capsule, including quercetin, luteolin, cryptotanshinone, etc. 11,432 heart failure disease targets, 249 genes intersecting with drugs, including the core targets containing TP53, STAT3, JUN, MAPK1, etc. These genes are mainly involved in the AGE-RAGE, fluid shear stress, and atherosclerosis, PI3K-Akt signaling pathways. Conclusion: This study initially revealed the multi-component, multi-target, multi-pathway mechanism of action of Qili Qiangxin Capsule in the treatment of heart failure, which provides a theoretical basis for further research.

Fluid shear stress-mediated Piezo1 alleviates osteocyte apoptosis by activating the PI3K/Akt pathway

Glucocorticoid-induced osteoporosis serves as a primary cause for secondary osteoporosis and fragility fractures, representing the most prevalent adverse reaction associated with prolonged glucocorticoid use. In this study, to elucidate the impact and underlying mechanisms of fluid shear stress (FSS)-mediated Piezo1 on dexamethasone (Dex)-induced apoptosis, we respectively applied Dex treatment for 6 h, FSS at 9 dyne/cm2 for 30 min, Yoda1 treatment for 2 h, and Piezo1 siRNA transfection to intervene in MLO-Y4 osteocytes. Western blot analysis was used to assess the expression of Cleaved Caspase-3, Bax, Bcl-2, and proteins associated with the PI3K/Akt pathway. Additionally, qRT-PCR was utilized to quantify the mRNA expression levels of these molecules. Hoechst 33258 staining and flow cytometry were utilized to evaluate the apoptosis levels. The results indicate that FSS at 9 dyne/cm2 for 30 min significantly upregulates Piezo1 in osteocytes. Following Dex-induced apoptosis, the phosphorylation levels of PI3K and Akt are markedly suppressed. FSS-mediated Piezo1 exerts a protective effect against Dex-induced apoptosis by activating the PI3K/Akt pathway. Additionally, downregulating the expression of Piezo1 in osteocytes using siRNA exacerbates Dex-induced apoptosis. To further demonstrate the role of the PI3K/Akt signaling pathway, after intervention with the PI3K pathway inhibitor, the activation of the PI3K/Akt pathway by FSS-mediated Piezo1 in osteocytes was significantly inhibited, reversing the anti-apoptotic effect. This study indicates that under FSS, Piezo1 in MLO-Y4 osteocytes is significantly upregulated, providing protection against Dex-induced apoptosis through the activation of the PI3K/Akt pathway.

FGL2/FcγRIIB Signalling Mediates Arterial Shear Stress-Mediated Endothelial Cell Apoptosis: Implications for Coronary Artery Bypass Vein Graft Pathogenesis.

The sudden exposure of venous endothelial cells (vECs) to arterial fluid shear stress (FSS) is thought to be a major contributor to coronary artery bypass vein graft failure (VGF). However, the effects of arterial FSS on the vEC secretome are poorly characterised. We propose that analysis of the vEC secretome may reveal potential therapeutic approaches to suppress VGF. Human umbilical vein endothelial cells (HUVECs) pre-conditioned to venous FSS (18 h; 1.5 dynes/cm2) were exposed to venous or arterial FSS (15 dynes/cm2) for 24 h. Tandem Mass Tagging proteomic analysis of the vEC secretome identified significantly increased fibroleukin (FGL2) in conditioned media from HUVECs exposed to arterial FSS. This increase was validated by Western blotting. Application of the NFκB inhibitor BAY 11-7085 (1 µM) following pre-conditioning reduced FGL2 release from vECs exposed to arterial FSS. Exposure of vECs to arterial FSS increased apoptosis, measured by active cleaved caspase-3 (CC3) immunocytochemistry, which was likewise elevated in HUVECs treated with recombinant FGL2 (20 ng/mL) for 24 h under static conditions. To determine the mechanism of FGL2-induced apoptosis, HUVECs were pre-treated with a blocking antibody to FcγRIIB, a receptor FGL2 is proposed to interact with, which reduced CC3 levels. In conclusion, our findings indicate that the exposure of vECs to arterial FSS results in increased release of FGL2 via NFκB signalling, which promotes endothelial apoptosis via FcγRIIB signalling. Therefore, the inhibition of FGL2/FcγRIIB signalling may provide a novel approach to reduce arterial FSS-induced vEC apoptosis in vein grafts and suppress VGF.