Photo-responsive nanoporous liquid crystal polymer films for selective dye adsorption.

Photo-responsive nanoporous polymer films (AZOF-R(NC6)) have been developed by a template method based on a hydrogen-bonding supramolecular liquid crystal (LC) and a light-sensitive azobenzene LC crosslinker in this work. Anionic nanopores were obtained after the removal of template NC6 using KOH solution. The AZOF-R(NC6) demonstrates charge-selective dye adsorption and the maximum adsorption capacity for Rh6G is 504.6 mg g-1. The AZOF-R(NC6) film without UV light treatment shows a 32% higher adsorption capacity for Rh6G than the AZOF-R(NC6) film treated with UV light within the initial 10 min. In addition, UV light can trigger the release of the adsorbed dye from the polymer film due to the pore size change arising from the trans-cis isomerization. Besides, the used polymer film can be effectively regenerated using a HCl solution. Such functional polymer films with highly ordered nanopores and photo-responsive properties hold great promise in selective adsorption and mass separations.

Refined Qingkailing protects the in vitro neurovascular unit against oxygen-glucose deprivation and re-oxygenation-induced injury.

Since the proposal of the neurovascular unit (NVU) theory, it has become almost mandatory for neuroprotective medicines against ischaemic stroke (IS) to focus on this unit. Refined Qingkailing (RQKL) is a compound composed of hyodeoxycholic acid, geniposide, baicalin and cholic acid, which has shown great potential in the treatment of IS, but its effect on NVU has not been fully studied. The purpose of this study was to investigate the potential biological pathways that underlie the protective effects of RQKL against NVU damage induced by oxygen-glucose deprivation and re-oxygenation (OGD/R). Using in vitro OGD/R models, we looked into whether RQKL protects the NVU. In order to create an in vitro NVU that resembles IS, we created an OGD/R injury model using primary cultures of brain microvascular endothelial cells, neurons, and astrocytes. Based on our results, we present evidence, for the first time, that RQKL treatment of the injury caused by OGD/R significantly (1) kept the blood brain barrier (BBB) functioning and maintained the architecture of the neurons, (2) mitigated the oxidative stress damage, inflammatory cytokine release, and neuronal death, and (3) upregulated the expression of neurotrophic factors generated from glial cells and the brain in the in vitro model. Therefore, RQKL has a variety of preventive effects against NVU damage caused by OGD/R. RQKL may be a suitable medication for treating IS in a clinical setting.

Protective effects of Scutellariae Radix Carbonisata-derived carbon dots on blood-heat and hemorrhage rats.

As the charcoal processing product of Scutellariae Radix (SR), SR Carbonisata (SRC) has been clinically used as a cooling blood and hemostatic agent for thousands of years. However, the underlying active ingredients and mechanism of SRC still remained unspecified. In this study, SRC derived carbon dots (SRC-CDs) were extracted and purified from the aqueous solution of SRC, followed by physicochemical property assessment by series of technologies. The cooling blood and hemostatic effects of SRC-CDs were further evaluated via a blood-heat and hemorrhage (BHH) rat model. Results showed that the diameters of obtained fluorescent SRC-CDs ranged from 5.0 nm to 10.0 nm and possessed functional group-rich surfaces. Additionally, the as-prepared SRC-CDs showed remarkable cooling blood and hemostasis effects in BHH model, mainly manifested by significant improvement of elevated rectal temperature, inflammatory cytokines (TNF-α, IL-6, and IL-1ß) levels, as well as protein expressions of myD88 and NF-κB p65, abnormal coagulation parameters (elevated APTT and FIB), hemogram parameters (RBC, HGB, and HCT), and histopathological changes in lung and gastric tissues. This study, for the first time, demonstrated that SRC-CDs were the cooling blood and hemostatic active components of SRC, which could inhibit the release of inflammatory cytokines by regulating myD88/NF-κB signaling pathway, and activating the fibrin system and endogenous coagulation pathway. These results not only provide a new perspective for the study of active ingredients of carbonized herbs represented by SRC, but also lay an experimental foundation for the development of next-generation nanomedicines.

The Retrieval and Effect of Core Parameters for Near-Field Inter-Body Coupling Communication.

The potential of the Internet of Body (IoB) to support healthcare systems in the future lies in its ability to enable proactive wellness screening through the early detection and prevention of diseases. One promising technology for facilitating IoB applications is near-field inter-body coupling communication (NF-IBCC), which features lower power consumption and higher data security when compared to conventional radio frequency (RF) communication. However, designing efficient transceivers requires a profound understanding of the channel characteristics of NF-IBCC, which remain unclear due to significant differences in the magnitude and passband characteristics of existing research. In response to this problem, this paper clarifies the physical mechanisms of the differences in the magnitude and passband characteristics of NF-IBCC channel characteristics in existing research work through the core parameters that determine the gain of the NF-IBCC system. The core parameters of NF-IBCC are extracted through the combination of transfer functions, finite element simulations, and physical experiments. The core parameters include the inter-body coupling capacitance (CH), the load impedance (ZL), and the capacitance (Cair), coupled by two floating transceiver grounds. The results illustrate that CH, and particularly Cair, primarily determine the gain magnitude. Moreover, ZL mainly determines the passband characteristics of the NF-IBCC system gain. Based on these findings, we propose a simplified equivalent circuit model containing only core parameters, which can accurately capture the gain characteristics of the NF-IBCC system and help to concisely describe the channel characteristics of the system. This work lays a theoretical foundation for developing efficient and reliable NF-IBCC systems that can support IoB for early disease detection and prevention in healthcare applications. The potential benefits of IoB and NF-IBCC technology can, thus, be fully realized by developing optimized transceiver designs based on a comprehensive understanding of the channel characteristics.

Novel in vivo endometriotic models associated eutopic endometrium by implanting menstrual blood-derived stromal cells from patients with endometriosis.

The eutopic endometrium provides novel insights into endometriotic pathophysiology and treatment. However, no in vivo models currently available are suitable for eutopic endometrium in endometriosis. In this study, we present new endometriotic in vivo models associated with eutopic endometrium using menstrual blood-derived stromal cells (MenSCs). First, we isolated endometriotic MenSCs (E-MenSCs) and healthy MenSCs (H-MenSCs) from the menstrual blood of patients with endometriosis (n = 6) and healthy volunteers (n = 6). Then, we identified MenSCs' endometrial stromal cell properties using adipogenic and osteogenic differentiation. A cell counting kit-8 and wound healing assay were used to compare the proliferation and migration capability between E-MenSCs and H-MenSCs. Seventy female nude mice were used to prepare endometriotic models related to eutopic endometrium by implanting E-MenSCs relying on three approaches, including surgical implantation using scaffolds seeded with MenSCs, and subcutaneous injection of MenSCs in the abdomen and the back (n = 10). H-MenSCs or scaffolds only were implanted in control groups (n = 10). One month after the surgical implantation and 1 week after the subcutaneous injection, we evaluated modeling by hematoxylin-eosin (H&E) and immunofluorescent staining of human leukocyte antigen α (HLAA). Fibroblast morphology, lipid droplets, and calcium nodules in E-MenSCs and H-MenSCs identified their endometrial stromal cell properties. We noticed that the proliferation and migration of E-MenSCs were considerably enhanced compared to H-MenSCs (P < 0.05). E-MenSCs implanted in nude mice formed ectopic lesions using three approaches (n = 10; lesions formation rate: 90%, 115%, and 80%; average volumes: 123.60, 27.37, and 29.56 mm3), while H-MenSCs in the nude mice shaped nothing at the implantation sites. Endometrial glands, stroma, and HLAA expression in these lesions further verified the success and applicability of the proposed endometriotic modeling. Findings provide in vitro and in vivo models and paired controls associated with eutopic endometrium in women with endometriosis using E-MenSCs and H-MenSCs. The approach of subcutaneous injection of MenSCs in the abdomen is highlighted due to non-invasive, simple, and safe steps, a short modeling period (1 week), and an excellent modeling success rate (115%), which could improve the repeats and success of endometriotic nude mice model and shorten the modeling period. These novel models could nearly intimate human eutopic endometrial mesenchymal stromal cells in the progress of endometriosis, opening a new path for disease pathology and treatment.

Emerging effects of non-coding RNA in vascular endothelial cells during strokes.

Vascular and neurological damage are the typical outcomes of ischemic strokes. Vascular endothelial cells (VECs), a substantial component of the blood-brain barrier (BBB), are necessary for normal cerebrovascular physiology. During an ischemic stroke (IS), changes in the brain endothelium can lead to a BBB rupture, inflammation, and vasogenic brain edema, and VECs are essential for neurotrophic effects and angiogenesis. Non-coding RNAs (nc-RNAs) are endogenous molecules, and brain ischemia quickly changes the expression patterns of several non-coding RNA types, such as microRNA (miRNA/miR), long non-coding RNA (lncRNA), and circular RNA (circRNA). Furthermore, vascular endothelium-associated nc-RNAs are important mediators in the maintenance of healthy cerebrovascular function. In order to better understand how VECs are regulated epigenetically during an IS, in this review, we attempted to assemble the molecular functions of nc-RNAs that are linked with VECs during an IS.

High-Performance Plant Pest and Disease Detection Based on Model Ensemble with Inception Module and Cluster Algorithm.

Protecting crop yields is the most important aspect of agricultural production, and one of the important measures in preserving yields is the control of crop pests and diseases; therefore, the identification of crop pests and diseases is of irreplaceable importance. In recent years, with the maturity of computer vision technology, more possibilities have been provided for implementing plant disease detection. However, although deep learning methods are widely used in various computer vision tasks, there are still limitations and obstacles in practical applications. Traditional deep learning-based algorithms have some drawbacks in this research area: (1) Recognition accuracy and computational speed cannot be combined. (2) Different pest and disease features interfere with each other and reduce the accuracy of pest and disease diagnosis. (3) Most of the existing researches focus on the recognition efficiency and ignore the inference efficiency, which limits the practical production application. In this study, an integrated model integrating single-stage and two-stage target detection networks is proposed. The single-stage network is based on the YOLO network, and its internal structure is optimized; the two-stage network is based on the Faster-RCNN, and the target frame size is first clustered using a clustering algorithm in the candidate frame generation stage to improve the detection of small targets. Afterwards, the two models are integrated to perform the inference task. For training, we use transfer learning to improve the model training speed. Finally, among the 37 pests and 8 diseases detected, this model achieves 85.2% mAP, which is much higher than other comparative models. After that, we optimize the model for the poor detection categories and verify the generalization performance on open source datasets. In addition, in order to quickly apply this method to real-world scenarios, we developed an application embedded in this model for the mobile platform and put the model into practical agricultural use.

Linking Nonalcoholic Fatty Liver Disease and Brain Disease: Focusing on Bile Acid Signaling.

A metabolic illness known as non-alcoholic fatty liver disease (NAFLD), affects more than one-quarter of the world's population. Bile acids (BAs), as detergents involved in lipid digestion, show an abnormal metabolism in patients with NAFLD. However, BAs can affect other organs as well, such as the brain, where it has a neuroprotective effect. According to a series of studies, brain disorders may be extrahepatic manifestations of NAFLD, such as depression, changes to the cerebrovascular system, and worsening cognitive ability. Consequently, we propose that NAFLD affects the development of brain disease, through the bile acid signaling pathway. Through direct or indirect channels, BAs can send messages to the brain. Some BAs may operate directly on the central Farnesoid X receptor (FXR) and the G protein bile acid-activated receptor 1 (GPBAR1) by overcoming the blood-brain barrier (BBB). Furthermore, glucagon-like peptide-1 (GLP-1) and the fibroblast growth factor (FGF) 19 are released from the intestine FXR and GPBAR1 receptors, upon activation, both of which send signals to the brain. Inflammatory, systemic metabolic disorders in the liver and brain are regulated by the bile acid-activated receptors FXR and GPBAR1, which are potential therapeutic targets. From a bile acid viewpoint, we examine the bile acid signaling changes in NAFLD and brain disease. We also recommend the development of dual GPBAR1/FXR ligands to reduce side effects and manage NAFLD and brain disease efficiently.

Shexiang Tongxin Dropping Pills Promote Macrophage Polarization-Induced Angiogenesis Against Coronary Microvascular Dysfunction via PI3K/Akt/mTORC1 Pathway.

Background: Accumulating evidence suggests that coronary microvascular dysfunction (CMD) is one of the important causes of coronary artery diseases. Angiogenesis can effectively improve CMD by increasing blood supply capacity, recovering cardiac function and poor hemodynamics. Clinical studies have approved Shexiang Tongxin dropping pill (STDP), which has exerted remarkable roles on ameliorating CMD, but the effects and mechanisms of STDPs on angiogenesis have not been clarified. Purpose: The purpose of this study was to elucidate the effects and potential mechanisms of STDPs on macrophage polarization-induced angiogenesis against CMD. Methods: Echocardiography, optical microangiography (OMAG), and histological examination were applied to evaluate cardioprotection and proangiogenic effects of STDPs on left anterior descending (LAD) ligation-induced CMD rats. In vitro, oxygen-glucose deprivation-reperfusion (OGD/R)-induced HUVEC model and LPS-stimulated bone marrow-derived macrophage (BMDM) model were established to observe the effects of STDPs on angiogenesis and M2 macrophage polarization. Results: STDPs improved cardiac function, increased microvascular density, and the number of M2 macrophages in the heart of CMD rats. In vitro, STDPs accelerated the proliferation, migration, and tube formation in OGD/R-induced HUVECs similar to the effects of VEGF-A. Furthermore, in LPS-stimulated BMDMs model, STDPs modulated M2 macrophage polarization and increased VEGF-A release via the PI3K/AKT/mTORC1 pathway. Conclusion: STDPs promoted macrophage polarization-induced angiogenesis against CMD via the PI3K/Akt/mTORC1 pathway. Our results demonstrated that the phenotype transformation of macrophages and stimulating the secretion of VEGF-A may be applied as novel cardioprotective targets for the treatment of CMD.

Photon-counting schemes for MIMO underwater wireless optical communication with arrayed PMTs.

Underwater wireless optical communication (UWOC) is a promising means of realizing large capacity and high rate in aquatic media. In this paper, a photomultiplier tube (PMT)-based multiple-input multiple-output (MIMO) UWOC system is investigated. Photon counting is an effective technique used to detect very low-level light. A PMT with an excellent photon-counting mode is adopted, and the performance in terms of the bit error rate is discussed. The received optical power can be predicted based on the detected photocount in each symbol period, and the received photocount distribution may be simulated through MATLAB. Furthermore, the optical link model and energy per bit with on-off keying are evaluated for different water types at a 10 m optical link distance. This MIMO-UWOC system combines the advantages of PMTs and the MIMO scheme and has the potential to realize long-distance optical link transmission.

Spatial distribution and potential sources of arsenic and water-soluble ions in the snow at Ili River Valley, China.

Trace elements and water-soluble ions in snow can be used as indicators to reveal natural and anthropogenic emissions. To understand the chemical composition, characteristics of snow and their potential sources in the Ili River Valley (IRV), snow samples were collected from 17 sites in the IRV from December 2018 to March 2019. Inverse distance weighting, enrichment factor (EF) analysis, and backward trajectory modelling were applied to evaluate the spatial distributions and sources of water-soluble ions and dissolved arsenic (As) in snow. The results indicate that Ca2+ and SO42- were the dominant ions, and the concentrations of As ranged from 0.09 to 0.503 µg L-1. High concentrations of As were distributed in the northwest and middle of the IRV, and the concentrations of the major ions were high in the west of the IRV. The strong correlation of As with F-, SO42-, and NO2- demonstrates that As mainly originated from coal-burning and agricultural activities. Principal component analysis showed that the ions originated from a combination of anthropogenic and crustal sources. The EFs showed that K+, SO42-, and Mg2+ were mainly influenced by human activities. Backward trajectory cluster analysis suggested that the chemical composition of snow was affected by soil dust transport from the western air mass, the unique terrain, and local anthropogenic activities. These results provide important scientific insights for atmospheric environmental management and agricultural production within the IRV.

Exploring the pharmacological mechanism of calculus bovis in cerebral ischaemic stroke using a network pharmacology approach.

ETHNOPHARMACOLOGICAL RELEVANCE: Calculus bovis is commonly used in traditional Chinese medicine for the treatment of cerebrovascular diseases given its roles in clearing away heat, detoxification and pain relief. Calculus bovis is used the treatment of cerebral ischaemia, liver and gallbladder diseases and various inflammatory conditions. However, the mechanism of action of calculus bovis in the treatment of ischaemic stroke is not well understood. AIM OF THE STUDY: In this study, the anti-inflammatory, antioxidative and antiapoptotic effects of calculus bovis on neurovascular units were studied, and the mechanism of action of calculus bovis on neurovascular units was also discussed. MATERIALS AND METHODS: Neurons, astrocytes, and endothelial cells were used to construct models of brain neurovascular units in vitro. The oxygen-glucose deprivation/reoxygenation and glucose (OGD/R) model was used to assess the effects of in vitro cultured calculus bovis on inflammatory factors, oxidative stress, and apoptosis. ZO-1, Occludin, Claudin-5, HIF-1, VEGF, PI3K, Akt, Bax, Bcl-2, and Caspase-3 expression was detected. RESULTS: In vitro cultured calculus bovis protects the blood-brain barrier; repairs tight junction proteins; increases ZO-1, Occludin and Claudin-5 protein expression; maintains TEER(transepithelial electrical resistance) values; repairs damaged endothelial cells; increases γ-GT activity; reduces LDH and inflammatory injury; and reduces TNF-α, LI-6, and IL-1ß levels. In vitro cultured calculus bovis reduces oxidative stress damage and NO and improves SOD activity. In vitro cultured calculus bovis protects neurons through antiapoptotic activities, including reductions in the apoptotic proteins Bax and Caspase-3, increases in Bcl-2 protein expression, and protection of brain neurovascular units through the HIF/VEGF and PI3K/Akt signalling pathways. CONCLUSION: In summary, the protective effect of calculus bovis on neurovascular units is achieved through antioxidative, anti-inflammatory and antiapoptotic effects. The mechanism of action of in vitro cultured calculus bovis in ischaemic stroke involves multiple targets and signalling pathways. The PI3K/Akt, HIF-1α and VEGF pathways effectively protect neurovascular units in the brain.

ß-elemene blocks lipid-induced inflammatory pathways via PPARß activation in heart failure.

This study aims to investigate the effects of ß-elemene on a mouse model of heart failure (HF) and to elucidate the underlying mechanisms in vitro approaches. In this study, left anterior descending (LAD)-induced HF mouse model and oxygen-glucose deprivation/recovery (OGD/R)-induced H9C2 model were leveraged to assess the therapeutic effects of ß-elemene. Histological examination, western blot and quantitative real-time PCR analysis (RT-qPCR) and immunofluorescence staining was utilized to elucidate mechanism of ß-elemene in lipid-induced inflammation. Results showed that ß-elemene improved heart function in HF mice evidenced by the increase of cardiac ejection fraction (EF) and fractional shortening (FS) values. Furthermore, ß-elemene administration rescued ventricular dilation, lipid accumulation, and inflammatory infiltration in arginal areas of mice myocardial infarction. At transcription level, ß-elemene augmented the mRNA expression of fatty acid oxidation-associated genes, such as peroxisome proliferator-activated receptor-ß (PPARß). In vitro, treatment of ß-elemene increased carnitine palmitoyltransferase 1A (CPT1A) and sirtuin 3 (SIRT3). Hallmarks of inflammation including the nuclear translocation of nuclear factor κB (NF-κB) and the degradation of inhibitory κBα (IκBα) were significantly suppressed. Consistently, we observed down-regulation of interleukin-6 (IL-6) and pro-inflammatory cytokines (such as TNFα) in ß-elemene treated H9C2 cells. Finally, molecular docking model predicted an interaction between ß-elemene and PPARß protein. Furthermore, ß-elemene increased the expression of PPARß, which was validated by antagonist of PPARß and siRNA for PPARß.

Baicalin Attenuates Oxygen-Glucose Deprivation/Reoxygenation-Induced Injury by Modulating the BDNF-TrkB/PI3K/Akt and MAPK/Erk1/2 Signaling Axes in Neuron-Astrocyte Cocultures.

Background: Baicalin (BCL), a candidate drug for ischemic stroke, has been indicated to protect neurons by promoting brain-derived neurotrophic factor (BDNF). However, the cellular source of BDNF release promoted by baicalin and its detailed protective mechanism after ischemia/reperfusion remains to be studied. The aim of this study was to investigate the neuroprotective mechanisms of baicalin against oxygen-glucose deprivation/reoxygenation (OGD/R) in a neuron-astrocyte coculture system and to explore whether the BDNF-TrkB pathway is involved. Methods and Results: A neuron-astrocyte coculture system was established to elucidate the role of astrocytes in neurons under OGD/R conditions. The results demonstrated that astrocytes became reactive astrocytes and released more BDNF in the coculture system to attenuate neuronal apoptosis and injury after OGD/R. BCL maintained the characteristics of reactive astrocytes and obviously increased the expression of cyclic AMP response element-binding protein (CREB) and the levels of BDNF in the coculture system after OGD/R. To further verify whether BDNF binding to its receptor tyrosine kinase receptor B (TrkB) was required for the neuroprotective effect of baicalin, we examined the effect of ANA-12, an antagonist of TrkB, on NA system injury, including oxidative stress, inflammation, and apoptosis induced by OGD/R. The results showed that treatment of NA systems with ANA-12 significantly attenuated the neuroprotection of BCL. The phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) and mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathways are two important downstream cascades of signaling pathways activated by BDNF binding to TrkB. We investigated the expressions of TrkB, PI3K, Akt, MAPK, and ERK. The results demonstrated that baicalin significantly increased the expressions of TrkB, PI3K/AKT, and MAPK/ERK. Conclusion: The neuroprotective effects of baicalin against oxidative stress, inflammation, and apoptosis were improved by astrocytes, mainly mediated by increasing the release of BDNF and its associated receptor TrkB and downstream signaling regulators PI3K/Akt and MAPK/ERK1/2.

Electrochemical aptasensor based on Mo2C/Mo2N and gold nanoparticles for determination of chlorpyrifos.

Two-dimensional Mo2C/Mo2N composites were synthesized by high temperature ball milling and used as support materials for fabricating a chlorpyrifos (CPF) aptasensor. Gold nanoparticles (Au NPs) were electrodeposited on the surface of a Mo2C/Mo2N-modified electrode to connect with the ferrocene (Fc) probe via Au-S bonds. The Fc probe can hybridize with the aptamer probe to form a double-stranded structure. The addition of CPF made the double strands melt and the Fc probe approached the surface of the electrode, thereby resulting in amplification of the electrochemical response. The current response of the aptasensor for detecting CPF in solutions linearly varied from 0 to 400 ng mL-1 (with a maximum at 0.98 V vs. Ag/AgCl). The Au NPs/Mo2C/Mo2N composites exhibited satisfactory electrochemical behavior due to their excellent electrical conductivity and large surface area. This ultrasensitive aptasensor showed a low limit of detection of 0.036 ng mL-1. It was applied to determine CPF in real samples with acceptable recoveries from 94.7 to 116.7%, and the relative standard deviation was from 2.57 to 7.08%.Graphical abstract Schematic diagram of the manufacturing process of the aptasensor. Electrochemical aptasensor based on Mo2C/Mo2N/Au NP composites show excellent performance in detecting CPF.

The multi-faceted role of retinoid X receptor in cardiovascular diseases.

Retinoid X receptors (RXRs) are members of ligand-dependent transcription factors whose effects on a diversity of cellular processes, including cellular proliferation, the immune response, and lipid and glucose metabolism. Knock out of RXRα causes a hypoplasia of the myocardium which is lethal during fetal life. In addition, the heart maintains a well-orchestrated balances in utilizing fatty acids (FAs) and other substrates to meet the high energy requirements. As the master transcriptional regulators of lipid metabolism, RXRs become particularly important for the energy needs of the heart. Accumulating evidence suggested that RXRs may exert direct beneficial effects in the heart both through heterodimerization with other nuclear receptors (NRs) and homodimerization, thus standing as suitable targets for treating in cardiovascular diseases. Although compounds that target RXRs are promising drugs, their use is limited by toxicity. A better understanding of the structural biology of RXRs in cardiovascular disease should enable the rational design of more selective nuclear receptor modulators to overcome these problems. Here, this review summarizes a brief overview of RXRs structure and versatility of RXR action in the control of cardiovascular diseases. And we also discussed the therapeutic potential of RXR ligand.

RNA-Seq Profiling to Investigate the Mechanism of Qishen Granules on Regulating Mitochondrial Energy Metabolism of Heart Failure in Rats.

Background. Qishen granules (QSG) are a frequently prescribed formula with cardioprotective properties prescribed to HF for many years. RNA-seq profiling revealed that regulation on cardiac mitochondrial energy metabolism is the main therapeutic effect. However, the underlying mechanism is still unknown. In this study, we explored the effects of QSG on regulating mitochondrial energy metabolism and oxidative stress through the PGC-1α/NRF1/TFAM signaling pathway. RNA-seq technology revealed that QSG significantly changed the differential gene expression of mitochondrial dysfunction in myocardial ischemic tissue. The mechanism was verified through the left anterior descending artery- (LAD-) induced HF rat model and oxygen glucose deprivation/recovery- (OGD/R-) established H9C2 induction model both in vivo and in vitro. Echocardiography and HE staining showed that QSG could effectively improve the cardiac function of rats with myocardial infarction in functionality and structure. Furthermore, transcriptomics revealed QSG could significantly regulate mitochondrial dysfunction-related proteins at the transcriptome level. The results of electron microscopy and immunofluorescence proved that the mitochondrial morphology, mitochondrial membrane structural integrity, and myocardial oxidative stress damage can be effectively improved after QSG treatment. Mechanism studies showed that QSG increased the expression level of mitochondrial biogenesis factor PGC-1α/NRF1/TFAM protein and regulated the balance of mitochondrial fusion/fission protein expression. QSG could regulate mitochondrial dysfunction in ischemia heart tissue to protect cardiac function and structure in HF rats. The likely mechanism is the adjustment of PGC-1α/NRF1/TFAM pathway to alleviate oxidative stress in myocardial cells. Therefore, PGC-1α may be a potential therapeutic target for improving mitochondrial dysfunction in HF.

Cholic Acid Protects In Vitro Neurovascular Units against Oxygen and Glucose Deprivation-Induced Injury through the BDNF-TrkB Signaling Pathway.

Ischemic stroke (IS) can disrupt various types of brain cells in the neurovascular unit (NVU) at both the structural and functional levels. Therefore, NVU is considered to be a more comprehensive target for the treatment of IS. It is necessary to develop drugs which targeted multiple mechanisms and cell types on NVU against IS. As a component of bile acid, cholic acid has been reported to be able to diffuse across phospholipid bilayers and further cross the blood-brain barrier (BBB). However, the effects exerted by cholic acid (CA) on the NVU after stroke remain unclear. Based on our previous research, we established and further supplemented the characteristics of the functional in vitro NVU model and its oxygen-glucose deprivation and reoxygenation (OGD/R) model. Then, we investigated the effect of CA on the maintenance of the in vitro NVU after OGD/R and further discussed the specific molecular targets that CA played a role in. For the first time, we found that CA significantly maintained BBB integrity, downregulated apoptosis, and mitigated oxidative stress and inflammation damage after OGD/R. Meanwhile, CA obviously increased the levels of brain-derived neurotrophic factor (BDNF), which were mainly secreted from astrocytes, in the coculture system after OGD/R. The results demonstrated that CA significantly increased the expression of TrkB, PI3K/Akt, MAPK/Erk, and CREB in neurons. These positive effects on the downstream proteins of BDNF were suppressed by treatment with ANA12 which is an inhibitor of TrkB. In conclusion, the present study demonstrates that CA exerted multiple protective effects on the NVU, mediated by increasing the release of BDNF and further stimulating the BDNF-TrkB-PI3K/Akt and BDNF-TrkB-MAPK/Erk signaling pathways in the context of OGD/R-induced injury. These findings indicate that CA possesses the effect of antagonizing multiple mechanisms of IS and protecting multiple cell types in NVU and may be useful as a treatment for IS.