Let-7a-5p abrogates progression of papillary thyroid carcinoma cells by decreasing nuclear receptor subfamily 6 group a member 1-mediated lipogenesis.

Increasing evidence shows that microRNAs (miRNAs) contribute vital roles in papillary thyroid carcinoma (PTC) carcinogenesis, proliferation, invasion, and so on. As the most common endocrine malignancy, there still have largely unknown molecular events. First, our analysis and open access database information indicates that the downregulation of let-7a-5p accelerates PTC progression. Next, lentivirus mediates the overexpression of let-7a-5p PTC cells, and found let-7a-5p suppressed cancer cells proliferation and invasion. Interestingly, bioinformatics analysis hints NR6A1 is the potential target gene of let-7a-5p. The regulation was validated by luciferase and quantitative reverse transcription polymerase chain reaction (qRT-PCR) in PTC tissue and the clinic tumors. Moreover, let-7a-5p regulated NR6A1 involved in PTC cells lipogensis in vitro and in vivo. Finally, let-7a-5p abrogates PCT xenograft tumors growth, NR6A1 expression and lipogenesis. Taken together, our data indicates that let-7a-5p suppresses PCT progression through decreased lipogenesis, the related let-7a-5p/NR6A1axis might be promising candidate targets for PTC treatment.

Effect of omega-3 fatty acids supplementation on the prognosis of coronary artery disease: A meta-analysis of randomized controlled trials.

AIMS: To evaluate whether omega-3 fatty acids (É·-3 FAs) supplementation can improve cardiovascular outcomes in patients with established coronary artery disease (CAD). DATA SYNTHESIS: Five electronic databases were searched for randomized controlled trials that evaluated the effect of É·-3 FAs on cardiovascular outcomes in patients with CAD. The language was restricted to English. The risk ratio was pooled. Subgroup analyses were conducted to evaluate whether study-level variables might act as effect modifiers. A total of 12 studies involving 29913 patients were included. É·-3 FAs had no effects on major adverse cardiovascular events (MACEs) (RR, 0.93; 95 % CI: 0.85 to 1.01, P = 0.09). While É·-3 FAs reduced the incidences of all-cause death (RR, 0.90; 95 % CI: 0.83 to 0.97, P = 0.005), cardiovascular death (RR, 0.82; 95 % CI: 0.75 to 0.90, P < 0.0001), myocardial infarction (RR, 0.77; 95 % CI: 0.68 to 0.86, P < 0.0001), revascularization (RR, 0.80; 95 % CI: 0.69 to 0.93, P = 0.003), sudden cardiac death (RR, 0.67; 95 % CI: 0.52 to 0.86, P = 0.002) and hospitalization for heart failure or unstable angina pectoris (RR, 0.75; 95 % CI: 0.58 to 0.97, P = 0.03) in CAD. It did not statistically reduce the risk of stroke (RR, 0.96; 95 % CI: 0.77 to 1.21, P = 0.76). The favorable effects of É·-3 FAs on MACEs were significant in subgroups of intervention with EPA and baseline triglyceride ≥1.7 mmol/L. CONCLUSION: É·-3 FAs supplementation, especially EPA, appears to be an effective adjunct therapy for improving the prognosis of CAD. REGISTRATION NUMBER: PROSPERO CRD42022311237.

CVTrack: Combined Convolutional Neural Network and Vision Transformer Fusion Model for Visual Tracking.

Most single-object trackers currently employ either a convolutional neural network (CNN) or a vision transformer as the backbone for object tracking. In CNNs, convolutional operations excel at extracting local features but struggle to capture global representations. On the other hand, vision transformers utilize cascaded self-attention modules to capture long-range feature dependencies but may overlook local feature details. To address these limitations, we propose a target-tracking algorithm called CVTrack, which leverages a parallel dual-branch backbone network combining CNN and Transformer for feature extraction and fusion. Firstly, CVTrack utilizes a parallel dual-branch feature extraction network with CNN and transformer branches to extract local and global features from the input image. Through bidirectional information interaction channels, the local features from the CNN branch and the global features from the transformer branch are able to interact and fuse information effectively. Secondly, deep cross-correlation operations and transformer-based methods are employed to fuse the template and search region features, enabling comprehensive interaction between them. Subsequently, the fused features are fed into the prediction module to accomplish the object-tracking task. Our tracker achieves state-of-the-art performance on five benchmark datasets while maintaining real-time execution speed. Finally, we conduct ablation studies to demonstrate the efficacy of each module in the parallel dual-branch feature extraction backbone network.

Light physical activity predicts long-term mortality in individuals with a different cardiovascular health status: a cohort study.

Studies have showed that LIPA seems to be favorably associated with mortality in the general population and illness individuals, but the association between different cardiovascular health status and mortality is not clear. After adjustment , the HRs of LIPA in individuals with CVRF and CVD from quartiles 2-4 were less than 1, which were 0.78 (95%CI, 0.61 ~ 0.99; P = 0.042), 0.63 (95%CI, 0.47 ~ 0.83; P = 0.001), 0.55（95%CI, 0.40 ~ 0.76; P < 0.001）, and 0.52 (95%CI, 0.37 ~ 0.74; P < 0.001)，0.39 (95%CI, 0.27 ~ 0.58; P < 0.001), 0.33 (95%CI, 0.22 ~ 0.51; P < 0.001) LIPA is beneficial for reducing mortality, but the shape of the association depends on cardiovascular health status.

Dithiolation of Alkenyl Sulfonium Salts with Arylthiols to Access 1,2-Dithioalkanes.

A dithiolation of alkenyl sulfonium salts with arylthiols is described, affording a series of 1,2-dithioalkanes in high yields. This protocol features mild and catalyst-free conditions and involves the formation of two C-S bonds sequentially via the regioselective addition of an arylthiol to the unsaturated C═C bonds, followed by the attack of another arylthiol to form 1,2-dithioalkanes exclusively.

Protective Effect of Anwulignan on Gastric Injury Induced by Indomethacin in Mice.

Anwulignan (AN) is a monomer lignan from Schisandra sphenanthera Rehd. et Wits (Schisandra sphenanthera fructus, Schisandra sphenanthera). The protective effect of AN against the indomethacin (IND)-induced gastric injury to mice and the related mechanism of action was investigated in this study. The effect of AN was mainly assessed by observing the gastric tissue morphology, gastric ulcer index (GUI), ulcer inhibition rate (UIR), gastric juice volume (GJV) and pH value. Chemical colorimetry, immunofluorescence, ELISA, and Western blot were used to detect related factors in the gastric tissue. The results showed that AN reduced the GUI, increased the UIR, inhibited the GJV, and increased the gastric pH value. AN significantly increased cyclooxygenase-1, cyclooxygenase-2, and prostaglandin E2 expression levels in the gastric tissue, activated nuclear factor (erythroid-derived 2)-like 2 (Nrf2), increased heme oxygenase-1 expression, enhanced the activity of superoxide dismutase and glutathione peroxidase, and decreased the malondialdehyde content. AN reduced the phosphorylation of nuclear factor-κ gene binding (NF-κB) p65 and its nuclear translocation, the key protein of NF-κB signaling pathway in the gastric tissue, and the content of the pathway downstream signaling molecules, including interleukin-6, interleukin-1ß, and tumor necrosis factor-α, to play an anti-inflammatory role. AN inhibited the downstream signals B-cell lymphoma 2-associated x protein and cleaved caspase-3 in gastric tissue, and activated B-cell lymphoma 2, to play an antiapoptotic role, which were further verified by Hoechst staining. Therefore, AN has a significant protection against the gastric injury induced by IND in mice, and the mechanism may be concerned in its activation of Nrf2, inhibition of NF-κB signaling pathway, and anti-apoptotic effect. SIGNIFICANCE STATEMENT: Anwulignan (AN) significantly reduced the indomethacin-induced gastric injury in mice, and its antioxidation, anti-inflammation, and antiapoptosis were considered to be involve in the effect, suggesting that AN should be a potential drug or food supplement for gastric injury induced by indomethacin.

Anwulignan Ameliorates the Intestinal Ischemia/Reperfusion.

Anwulignan is one of the monomer compounds in the lignans from Schisandra sphenanthera In this study, we observed the effect of anwulignan on intestinal ischemia/reperfusion (II/R) injury in male Sprague-Dawley rats and explored the underlying mechanisms. The results showed that pretreatment with oral anwulignan could significantly increase the mesenteric blood microcirculatory flow velocity; relieve the congestion and pathologic injury of jejunum; enhance the autonomic tension of jejunum smooth muscle and its reactivity to acetylcholine; increase the activities of superoxide dismutase, catalase, glutathione S-transferase, and choline acetyltransferase; increase the contents of acetylcholine and glutathione in the serum or jejunal tissue; decrease the activities of myeloperoxidase, protein kinase C, and nicotinamide adenine dinucleotide phosphate oxidase; reduce the contents of malondialdehyde, 8-hydroxy-2-deoxyguanosine, nicotinamide adenine, reactive oxygen species, tumor necrosis factor-α, interleukin (IL)-6, and IL-1ß; increase the expression levels of muscarinic receptor 3, PI3K, phosphorylation protein kinase B, p-GSK3ß Ser9, Nrf2, p-Nrf2, heme oxygenase (decycling) 1, and b-cell lymphoma 2 in the jejunal tissue; and decrease the expression levels of p-GSK3ß Tyr216, kelch-like ECH-associated protein 1, Bax, and cleaved caspase-3, suggesting that anwulignan can ameliorate II/R-induced jejunal tissue injury in rats and that the mechanism may be related to its activating the PI3K/protein kinase B pathway and then regulating the Nrf2/Anti-oxidative Response Element signaling pathway and the expression of apoptosis-related proteins to play antioxidant and antiapoptotic roles. SIGNIFICANCE STATEMENT: Anwulignan can significantly reduce jejunal tissue injury and the production of inflammatory factors in rats with intestinal ischemia-reperfusion injury, improve the antioxidant capacity, and reduce the apoptosis of jejunal tissue, and it has the effect of significantly improving intestinal ischemia-reperfusion injury in rats, suggesting that anwulignan may be used as a potential drug for the prevention and treatment of intestinal ischemia-reperfusion injury or a resource for the development of health food.

Long non-coding RNAs in cardiac hypertrophy.

Cardiac hypertrophy (CH) is generally considered adaptive responses that may occur after myocardial infarction, pressure overload, volume overload, inflammatory heart muscle disease, or idiopathic dilated cardiomyopathy, whereas long-term stimulation eventually leads to heart failure (HF). However, the current molecular mechanisms involved in CH are unclear. Recently, increasing evidences reveal that long non-coding RNAs (lncRNAs) play vital roles in CH. Different lncRNAs can promote or inhibit the pathological process of CH by different mechanisms, while the regulation of lncRNAs expression can improve CH. Thus, CH-related lncRNAs may become a novel field of research on CH.

Ginsenoside Re Preserves Cardiac Function and Ameliorates Left Ventricular Remodeling in a Rat Model of Myocardial Infarction.

Ginsenoside Re, an herbal ingredient from ginseng, has been demonstrated to protect the heart from various cardiovascular diseases. In this study, we investigated the protective effects and mechanisms of ginsenoside Re (Gin-Re) on cardiac function and left ventricular remodeling in a rat model of myocardial infarction (MI). After ligating the left anterior descending coronary artery, Wistar rats were treated with Gin-Re (135 mg/kg) by gavage everyday for 4 weeks. Serological detection showed that Gin-Re significantly inhibited myocardial injury and attenuated oxidative stress in MI rats. Echocardiographic observation showed that Gin-Re significantly improved cardiac function and prevented left ventricular dilatation induced by MI. Pathological observation found that Gin-Re significantly decreased interstitial fibrosis in the left ventricle of MI rats. Compared with the MI group, Gin-Re treatment promoted AMPKα phosphorylation, decreased TGF-ß1 expression, and attenuated Smad2/3 activation. After Gin-Re treatment, the phosphorylation of FAK, PI3K p110α, and Akt was enhanced in MI rats, while PI3K p110ß showed no difference compared with the MI group. These results indicate that Gin-Re may improve MI-induced cardiac dysfunction and mitigate ventricular remodeling through regulation of the AMPK/TGF-ß1/Smad2/3 and FAK/PI3K p110α/Akt signaling pathways.

Low-level shear stress induces differentiation of liver cancer stem cells via the Wnt/ß-catenin signalling pathway.

Shear stress-activated cellular signalling is involved in cellular migration, proliferation and differentiation. However, it remains unclear about the effects of shear stress on the differentiation of liver cancer stem cells (LCSCs). In this study, using a parallel plated flow chamber system, we found that low-shear stress loading (2 dyne/cm2) for 48 h could significantly inhibit the sphere-forming ability, increase the chemotherapeutic drug sensitivity, downregulate cancer stem cell marker expression and suppress the in vivo tumorigenicity potential of LCSCs. Moreover, using an atomic force microscope (AFM), we found that shear stress increased the Young's modulus of LCSCs. These results indicate LCSC's differentiation after shear stress exposure. In addition, low-shear stress loading suppressed the ß-catenin expression in LCSCs. More importantly, pharmacological activation of Wnt/ß-catenin signalling restored the shear stress-suppressed ß-catenin expression in LCSCs, and abolished the shear stress-altered sphere-forming ability, chemotherapeutic drug sensitivity, cancer stem cell marker expression, Young's modulus and in vivo tumorigenicity potential of LCSCs. Our results suggest that low shear stress could induce LCSC differentiation via the Wnt/ß-catenin signalling pathways, providing a new insight into the role of shear stress in cancer cell biological behaviors that might contribute to the development of new therapeutic strategies for liver cancer treatment.

Metabolic mapping of Schisandra chinensis lignans and their metabolites in rats using a metabolomic approach based on HPLC with quadrupole time-of-flight MS/MS spectrometry.

Schisandra chinensis lignans are the main active components of the traditional Chinese medicine Schisandra chinensis in East Asia. At present, there are more and more medicines and health foods in which the total S. chinensis lignans extracts are considered as the main active components, but little research has been done on the active components of S. chinensis lignans in the blood and main target organs. In this study, the components of S. chinensis lignans in the blood, liver and brain tissues of rats at different time points after the intragastrical administration of S. chinensis lignans were determined by a metabolomic method based on high-performance liquid chromatography with quadrupole time-of-flight tandem mass spectrometry spectrometry. Twelve Schisandra chinensis lignans and 15 metabolites in the blood, liver, and brain of rats were identified. The results showed that the main metabolic ways of S. chinensis lignans in rats were hydroxylation, demethylation, and demethylation-hydroxylation, and some of them might undergo demethylation, dehydrogenation, epoxidation, and elimination reaction. The time-dose characteristics of S. chinensis lignans and their metabolites in the blood and target organs were analyzed, which may be helpful to elucidate the active substances that really exert the pharmacodynamic effects of S. chinensis lignans in organisms.

Overexpression of circ_0005198 sponges miR-1294 to regulate cell proliferation, apoptosis, migration, and invasion in glioma.

Glioma (GM) is an aggressive malignancy with high mortality rate across the world. Mounting studies demonstrates that abnormally expressed circular RNAs (circRNAs) act as important roles in tumor progression. In the current work, a novel circRNA, circ_0005198, was explored. Circ_0005198 level in GM tissue samples and cells was detected. The clinical implication of circ_0005198 was analyzed by Fisher's test and Kaplan-Meier analysis. In vitro experiments were carried out to elucidate the influence of circ_0005198 on GM cell proliferation, apoptosis, and metastatic properties. Luciferase reporter and rescue experiments were conducted to clear the mechanism of circ_0005198. The expression of circ_0005198 was enhanced in GM tumors and cells. Its expression in tumor specimens was related to clinical severity and poor prognosis. Functionally, circ_0005198 could remarkably boost cell growth, clone-forming ability, and metastatic properties and attenuate cell apoptosis in GM cells. What's more, circ_0005198 could directly sponge miR-1294 to exert oncogenic functions. In summary, this study might provide an effective therapeutic target for GM.

Activation of the mammalian target of rapamycin signaling pathway underlies a novel inhibitory role of ring finger protein 182 in ventricular remodeling after myocardial ischemia-reperfusion injury.

Myocardial ischemia-reperfusion injury (MIRI) is a major cause of cardiovascular disease, leading to mortality and disability associated with coronary occlusion worldwide. A correlation of mammalian target of rapamycin (mTOR)/nuclear factor-kappa B (NF-κB) signaling pathway has been observed with brain damage resulting from myocardial ischemia. Therefore, by establishing MIRI rat model, this study aimed to explore whether ring finger protein 182 (RNF182) regulates the mTOR signaling pathway affecting MIRI. Initially, MIRI rat model was successfully established, followed by either treatment of shRNF182 or phosphoesterase (PITE) (inhibitor of the mTOR signaling pathway). Then, the serum levels of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and malondialdehyde (MDA), left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS), left ventricular systolic pressure (LVSP), and left ventricular end-diastolic pressure (LVEDP) were determined, followed by detection of myocardial infarct sizes and myocardial cell apoptosis. Moreover, the levels of related genes/proteins were determined to further determine the mechanisms of RNF182 in MIRI. First, RNF182 was upregulated in MIRI. Another key observation of this study was that rats with shRNF182 presented with downregulated SOD, GSH-Px, and MDA in serum, accompanied by decreased levels of LVEF, LVFS, LVSP, and LVEDP. In addition, both reduced myocardial infarct sizes and apoptosis of myocardial cells were observed after silencing RNF182. Furthermore, silencing of the RNF182 was observed to downregulate Bcl 2-associated X and cysteine proteinase 3 but upregulate mTOR, ribosome protein subunit 6 kinase 1, eukaryotic elongation factor 2, and B-cell lymphoma-2. Importantly, the effects of RNF182 silencing were reversed after PITE treatment. In conclusion, our study demonstrates that RNF182 silencing can prevent ventricular remodeling in rats after MIRI by activating the mTOR signaling pathway.

Cytoskeletal control of nuclear morphology and stiffness are required for OPN-induced bone-marrow-derived mesenchymal stem cell migration.

During cell migration, the movement of the nucleus must be coordinated with the cytoskeletal dynamics that influence the efficiency of cell migration. Our previous study demonstrated that osteopontin (OPN) significantly promotes the migration of bone-marrow-derived mesenchymal stem cells (BMSCs). However, the mechanism that regulates nuclear mechanics of the cytoskeleton during OPN-promoted BMSC migration remains unclear. In this study, we investigated how the actin cytoskeleton influences nuclear mechanics in BMSCs. We assessed the morphology and mechanics of the nuclei in the OPN-treated BMSCs subjected to disruption or polymerization of the actin cytoskeleton. We found that disruption of actin organization by cytochalasin D (Cyto D) resulted in a decrease in the nuclear projected area and nuclear stiffness. Stabilizing the actin assembly with jasplakinolide (JASP) resulted in an increase in the nuclear projected area and nuclear stiffness. SUN1 (Sad-1/UNC-84 1) is a component of the LINC (linker of nucleoskeleton and cytoskeleton) complex involved in the connections between the nucleus and the cytoskeleton. We found that SUN1 depletion by RNAi decreased the nuclear stiffness and OPN-promoted BMSC migration. Thus, the F-actin cytoskeleton plays an important role in determining the morphology and mechanical properties of the nucleus. We suggest that the cytoskeletal-nuclear interconnectivity through SUN1 proteins plays an important role in OPN-promoted BMSC migration.

Low shear stress induces ERK nuclear localization and YAP activation to control the proliferation of breast cancer cells.

Micro-environmental regulation of cancer cell malignancy is one of the most basic cancer life phenomena. However, the study of cellular response to microenvironment has been long focused on signal processes mediated by various chemical factors and their receptors, the study of mechanical forces, another key environmental factor, has been less studied. In recent years, more and more attention has been paid to the physiological and pathological significance of mechanical microenvironment. However, it is still not clear how cells perceive environmental changes and the signal pathways that regulate cell physiological activities. In this study, we identified that low shear stress (LSS) significantly promoted breast cancer cell proliferation. The proliferation was closely associated with mitogen-activated protein kinase (MAPK) extracellular signal-regulated kinase (ERK) and Yes-associated protein (YAP). Inhibition of ERK or YAP both abolished the LSS-induced proliferation activity of cancer cells. LSS induced ERK phosphorylation and YAP activations, which suggested the involvement of ERK and YAP under LSS treatment. Under LSS, ERK inhibitor U0126 decreased both active YAP and ERK expressions, while YAP inhibitor verteporfin failed to decrease ERK phosphorylation. Further study confirmed that ERK translocated to nucleus which showed an active state of ERK in LSS-treated group. LSS with verteporfin group showed no differences with LSS-treated group which confirmed ERK and YAP an upstream-downstream cascade. The above results demonstrated that LSS can promote breast cancer cell proliferation through ERK-YAP activation. These results not only highlight a new means of understanding mechanical transmission to cytoplasm mechanisms but also serve as a new basis for developing drug delivery systems for breast cancer treatment.

Cdc42-mediated supracellular cytoskeleton induced cancer cell migration under low shear stress.

Tumor microenvironment is composed of biological, chemical and physical factors. Mechanical factors are more and more focused these years. Therefore, mimicking mechanical factors' contribution to cancer cell malignancy will greatly improve the advance in this field. Although the induced malignant behaviors are present under many stimuli such as growth or inflammatory factors, the cell key physical migration mechanisms are still missing. In this study, we identify that low shear stress significantly promotes the formation of needle-shaped membrane protrusions, which is called filopodia and important for the sense and interact of a cell with extracellular matrix in the tumor microenvironment. Under low shear stress, the migration is promoted while it is inhibited in the presence of ROCK inhibitor Y27632, which could abolish the F-actin network. Using cell imaging, we further unravel that key to these protrusions is Cell division cycle 42 (Cdc42) dependent. After Cdc42 activation, the filopodia is more and longer, acting as massagers to pass the information from a cell to the microenvironment for its malignant phenotype. In the Cdc42 inhibition, the filopodia is greatly reduced. Moreover, small GTPases Cdc42 rather than Rac1 and Rho directly controls the filopodia formation. Our work highlights that low shear stress and Cdc42 activation are sufficient to promote filopodia formation, it not only points out the novel structure for cancer progression but also provides the experimental physical basis for the efficient drug anti-cancer strategies.

Pooling analysis regarding the impact of human vitamin D receptor variants on the odds of psoriasis.

BACKGROUND: The study aims at scientifically investigating the genetic effect of four polymorphisms (rs7975232, rs1544410, rs2228570, and rs731236) within the human Vitamin D Receptor (VDR) gene on the odds of psoriasis through an updated meta-analysis. METHODS: We searched eight databases and screened the studies for pooling. Finally, a total of eighteen eligible case-control studies were included. BH (Benjamini & Hochberg) adjusted P-values of association (Passociation) and odd ratios (ORs) with the corresponding 95% confidence intervals (CIs) were calculated under the allele, homozygote, heterozygote, dominant, recessive, and carrier models. RESULTS: Compared with the negative controls, no statistically significant difference in the odds of psoriasis was detected for the cases under any genetic models (BH adjusted Passociation > 0.05). We also performed subgroup meta-analyses by the source of controls, ethnicity, country, Hardy-Weinberg equilibrium, and genotyping method. Similar results were observed in most subgroup meta-analyses (BH adjusted Passociation > 0.05). Besides, data of Begg's and Egger's tests excluded the significant publication bias; while the sensitivity analysis data further indicated the statistical reliability of our pooling results. CONCLUSION: The currently available data fails to support a robust association between VDR rs7975232, rs1544410, rs2228570 and rs731236 polymorphisms and psoriasis susceptibility, which still required the support of more case-control studies.

Schisandra chinensis acidic polysaccharide partialy reverses acetaminophen-induced liver injury in mice.

Schisandra chinensis is a hepatoprotective herb that has been used for centuries in China. Polysaccharide is one of the major active components in S. chinensis, which has been reported to improve liver injuries induced by carbon tetrachloride, alcohol, or high-fat diet. In this study, we observed the effects and corresponding mechanisms of the secondary component of Schisandra polysaccharide (acidic polysaccharide, SCAP) on a murine model of severe acute liver injury induced by acetaminophen (APAP). SCAP significantly decreased the serum alanine aminotransferase (ALT), aspartate aminotransferas (AST), tumor necrosis factor-α (TNF-α), and interleukin-1ß (IL-1ß) levels, and was found to alleviate hepatic pathological alterations in the mouse model. Meanwhile, SCAP revealed a protective effects on the liver injury-related enzymes and factors, such as significantly diminished malondialdehyde (MDA) levels and glutathione (GSH) depletion, reduced ratio of B-cell lymphoma-2 (Bcl-2)-associated X protein (Bax)/Bcl-2, prohibited cleaved caspase-3 expression, and elevated the expression of p-AMPK, p-Akt, p-glycogen synthase kinase 3ß (GSK 3ß), nuclear factor erythroid 2-derived-like 2 (Nrf 2) and heme oxygenase-1 (HO-1) proteins in the liver tissues of the mouse model. In conclusion, we speculated that the protective activities of SCAP on the APAP-induced mouse model of acute liver injury might be related to its antioxidation, anti-inflammation and anti-apoptosis properties.

Pharmacokinetics and distribution of schisandrol A and its major metabolites in rats.

1. Schizandrol A is an active component in schisandra, also the representative component for the identification of schisandra. 2. A rapid resolution liquid chromatography coupled with quadruple-time-of-flight mass spectrometry (RRLC-QTOF/MS) was developed to investigate the pharmacokinetics of schizandrol A after its intragastric administration (50 mg/kg) in rats. 3. Schizandrol A was rapidly absorbed (T max = 2.07 h), with a longer duration (t 1/2 = 9.48 h) and larger apparent volume of distribution (Vz/F = 111.81 l/kg) in rats. Schizandrol A can be detected in main organs and the order of its distribution was in the liver > kidney > heart > spleen > brain, particularly higher in the liver. 4. Five schizandrol A metabolites were identified, including 2-demethyl-8(R)-hydroxyl-schizandrin, 3-demethyl-8(R)-hydroxyl-schizandrin, hydroxyl-schizandrin, demethoxy-schizandrin, 2, 3-demethyl-8(R)-hydroxyl-schizandrin, indicating that the hydroxylation and demethylation may be the major metabolic way of schizandrol A. 5. This study defined the pharmacokinetic characteristics of schizandrol A in vivo, and the RRLC-QTOF/MS is more sensitive and less limited by conditions, and needs less samples, which may be a useful resource for the further research and development of schisandrol A.

Decreased nuclear stiffness via FAK-ERK1/2 signaling is necessary for osteopontin-promoted migration of bone marrow-derived mesenchymal stem cells.

Migration of bone marrow-derived mesenchymal stem cells (BMSCs) plays an important role in many physiological and pathological settings, including wound healing. During the migration of BMSCs through interstitial tissues, the movement of the nucleus must be coordinated with the cytoskeletal dynamics, which in turn affects the cell migration efficiency. Our previous study indicated that osteopontin (OPN) significantly promotes the migration of rat BMSCs. However, the nuclear behaviors and involved molecular mechanisms in OPN-mediated BMSC migration are largely unclear. In the present study, using an atomic force microscope (AFM), we found that OPN could decrease the nuclear stiffness of BMSCs and reduce the expression of lamin A/C, which is the main determinant of nuclear stiffness. Increased lamin A/C expression attenuates BMSC migration by increasing nuclear stiffness. Decreased lamin A/C expression promotes BMSC migration by decreasing nuclear stiffness. Furthermore, OPN promotes BMSC migration by diminishing lamin A/C expression and decreasing nuclear stiffness via the FAK-ERK1/2 signaling pathway. This study provides strong evidence for the role of nuclear mechanics in BMSC migration as well as new insight into the molecular mechanisms of OPN-promoted BMSC migration.