[Matrine inhibits inflammatory response induced by TNF-α in human umbilical vein endothelial cells through miR-25-3p-mediated Klf4 pathway].

This study aimed to analyze the effect of matrine on tumor necrosis factor-α(TNF-α)-induced inflammatory response in human umbilical vein endothelial cells(HUVECs) and explore whether the underlying mechanism was related to the miR-25-3p-mediated Krüppel-like factor 4(Klf4) pathway. The HUVEC cell inflammation model was induced by TNF-α stimulation. After 24 or 48 hours of incubation with different concentrations of matrine(0.625, 1.25, and 2.5 mmol·L~(-1)), CCK-8 assay was used to detect cell proliferation. After treatment with 2.5 mmol·L~(-1) matrine for 48 h, the expression of TNF-α, interleukin-6(IL-6), interleukin-1ß(IL-1ß), and Klf4 mRNA and miR-25-3p was detected by real-time fluorescence-based quantitative PCR, and the protein expression of TNF-α, IL-6, IL-1ß, and Klf4 was detected by Western blot. The anti-miR-25-3p was transfected into HUVECs, and the effect of anti-miR-25-3p on TNF-α-induced cell proliferation and inflammatory factors was detected by the above method. The cells were further transfected with miR-25-3p and incubated with matrine to detect the changes in proliferation and expression of related inflammatory factors, miR-25-3p, and Klf4. The targeting relationship between miR-25-3p and Klf4 was verified by bioinformatics analysis and dual luciferase reporter gene assay. The results displayed that matrine could inhibit TNF-α-induced HUVEC proliferation, decrease the mRNA and protein expression of TNF-α, IL-6, and IL-1ß, increase the mRNA and protein expression of Klf4, and reduce the expression of miR-25-3p. Bioinformatics analysis showed that there were specific complementary binding sites between miR-25-3p and Klf4 sequences. Dual luciferase reporter gene assay confirmed that miR-25-3p negatively regulated Klf4 expression in HUVECs by targeting. The inhibition of miR-25-3p expression can reduce TNF-α-induced cell proliferation and mRNA and protein expression of TNF-α, IL-6, and IL-1ß. MiR-25-3p overexpression could reverse the effect of matrine on TNF-α-induced cell proliferation and the mRNA and protein expression of TNF-α, IL-6, IL-1ß, and Klf4. This study shows that matrine inhibits the inflammatory response induced by TNF-α in HUVECs through miR-25-3p-mediated Klf4 pathway.

Preterm Birth in China Between 2015 and 2016.

Objectives. To describe the incidence, risk factors, and potential causes of preterm birth (PTB) in China between 2015 and 2016.Methods. The China Labor and Delivery Survey was a population-based multicenter study conducted from 2015 to 2016. We assigned each birth a weight based on the sampling frame. We calculated the incidence of PTB and the multivariable logistic regression, and we used 2-step cluster analysis to examine the relationships between PTB and maternal, fetal, and placental conditions.Results. The weighted nationwide incidence of PTB was 7.3% of all births and 6.7% of live births at 24 or more weeks of gestation. Of the PTBs, 70.5% were born after 34 weeks and 42.7% were iatrogenic. Nearly two thirds of all preterm births were attributable to maternal, fetal, or placental conditions, and one third had unknown etiology.Conclusions. This study provided information on the incidence of PTB in China and identified several factors associated with PTB. The high frequency of iatrogenic PTB calls for a careful assessment and prudent management of such pregnancies, as PTB has short- and long-term health consequences.

Combined application of pharamcokinetic DCE-MRI and IVIM-DWI could improve detection efficiency in early diagnosis of ductal carcinoma in situ.

PURPOSE: Ductal carcinoma in situ (DCIS) is a precursor of invasive ductal breast carcinoma (IDC). This study aimed to use pharamcokinetic dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) for the early diagnosis of DCIS. METHODS: Forty-seven patients, including 25 with DCIS (age: 28-70 yr, mean age: 48.7 yr) and 22 with benign disease (age: 25-67 yr, mean age: 43.1 yr) confirmed by pathology, underwent pharamcokinetic DCE-MRI and IVIM-DWI in this study. The quantitative parameters Ktrans , Kep , Ve , Vp , and D, f, D* were obtained by processing of DCE-MRI and IVIM-DWI images with Omni-Kinetics and MITK-Diffusion softwares, respectively. Parameters were analyzed statistically using GraphPad Prism and MedCalc softwares. RESULTS: All low-grade DCIS lesions demonstrated mass enhancement with clear boundaries, while most middle-grade and high-grade DCIS lesions showed non-mass-like enhancement (NMLE). DCIS lesions were significantly different from benign lesions in terms of Ktrans , Kep , and D (t = 5.959, P < 0.0001; t = 5.679, P < 0.0001; and t = 5.629, P < 0.0001, respectively). The AUC of Ktrans , Kep , D and the combined indicator of Ktrans , Kep, and D were 0.936, 0.902, 0.860, and 0.976, respectively. There was a significant difference in diagnostic efficacy only between D and the combined indicator (Z = 2.408, P = 0.016). CONCLUSION: DCE-MRI and IVIM-DWI could make for the early diagnosis of DCIS, and reduce the misdiagnosis of DCIS and over-treatment of benign lesions.

[Oxymatrine alleviates oxidative stress in fat-induced insulin resistance mice by suppressing p38MAPK pathway].

This paper was aimed to investigate the effect of oxymatrine on fat-induced insulin resistance mice（IR）, and to explore the effects of oxymatrine on oxidative stress and on p38 mitogen activated protein kinase (p38MAPK) pathway. ApoE-/- mice with high fat diet for 16 weeks were selected as IR animal model and randomly divided into the model group, oxymatrine 25, 50, 100 mg•kg⁻¹ group. C57BL/6J mice were selected as the normal control group. Mice were gavage for 8 weeks. Fasting blood glucose (FBG), cholesterol (TC), triglyceride (TG), fatty acid (FFA) and serum insulin (FINS) in the plasma were detected. Activity of superoxide dismutase (SOD), glutathione peroxidase, glutathione peroxidase (GSH-Px) and content of malondialdehyde (MDA) in liver were detected. Reactive oxygen species (ROS) content in liver cells were detected by Flow cytometry. The expression of heme oxygenase-1(HO-1), γ-glutamyl cysteine synthetase (γ-GCS) of liver was examined by Real time PCR and Western blot. The protein expression of p38MAPK, p-p38MAPK was examined by Western blot. In the study, the authors found that oxymatrine reduced the levels of FBG, TC, TG and FFA, increased SOD and GSH-Px contents, decreased MDA and ROS content. Compared with model group, HO-1, γ-GCS mRNA and protein expression significantly increased in 50, 100 mg•kg⁻¹ oxymatrine group. The expression of p-p38MAPK decreased in oxymatrine group. The results showed that oxymatrine alleviate oxidative stress in hepatic by inhibiting the phosphorylation of p38MAPK, to ameliorate fat-induced insulin resistance mice.

[Effect of Jinlida on DGAT1 in Skeletal Muscle in Fat-Induced Insulin Resistance ApoE -/- Mice].

OBJECTIVE: To investigate the effect of Jinlida on DGAT1 in skeletal muscle in fat-induced insulin resistance ApoE-/- mice. METHODS: Eight male C57BL/6J mice were used as normal group. 40 male ApoE -/- mice were fed high-fat diet for 16 weeks and divided into five groups: control group, rosiglitazone group, and Jinlida low, middle and high dose groups. Then corresponding drugs were administrated intragastrically for eight weeks. TG content in skeletal muscle was measured by enzymic enzymatic, Glucose tolerance test (OGTT) was used to evaluate the degree of insulin resistance in mice. The mRNA and protein expression of insulin receptor substrate (IRS-1) and diacylglycerol acyltransferase 1 (DGAT1) in skeletal muscle were measured by real-time quantitative reverse transcription PCR (RT-PCR)and Western blot. RESULTS: Jinlida particles reduced fasting blood glucose (FBG) cholesterol (TC), triglyceride (TG), free fatty acid (FFA)and fasting insulin (FIns) levels, raised insulin sensitive index (ISI), improved glucose tolerance, and reduced skeletal muscle lipid deposition in ApoE -/- mice significantly. Jinlida particles increased the expression of IRS-1 mRNA and protein, and reduced DGAT1. CONCLUSION: Jinlida can alleviate the expression of DGAT in skeletal muscle in fat-induced insulin resistance ApoE-/- mice.

[Effects of Tongxinluo capsule on sciatic nerve apoptosis in spontaneous type II diabetic KK/Upj-Ay mice and mechanism research].

To investigate the effects of Tongxinluo capsule on sciatic nerve apoptosis in spontaneous type II diabetic KK/Upj-Ay mice, in order to explore its mechanism for improving diabetic peripheral neuropathy (DPN). KK/Upj-Ay mice were selected as the DPN animal model and randomly divided into the model, Tongxinluo low, middle and high group (1, 2, 4 g x kg(-1)). C57BL/6 mice were selected as the control group. Mice were given intragastrically for 12 weeks. Paw withdrawal latency, motor nerve conduction velocity (MNCV) and sensory nerve conduction velocity (SNCV) were detected. Apoptotic rate were detected by FCM. Bcl-2, Bax, Caspase-3 mRNA and protein expression in sciatic nerve were examined by Real-time PCR and Western blot. p38MAPK, p-p38MAPK expression were examined by Western blot. In this study,the authors found that Tongxinluo capsule could increase paw withdrawal latency, MNCV and SNCV. Apoptotic rate of sciatic, the expression of Bax and caspase-3 were lower, while Bcl-2 expression was higher in Tongxinluo group than those in model mice. The expression of p-p38MAPK significantly decreased in Tongxinluo group. The results showed that Tongxinluo capsule has protective effects on diabetic peripheral neuropathy of mice via inhibiting cell apoptosis and suppressing the expression of p-p38MAPK.

[Effect of Jinlida on changes in expression of skeletal muscle lipid transport enzymes in fat-induced insulin resistance ApoE -/- mice].

OBJECTIVE: To study the effect of Jinlida on changes in expression of skeletal muscle lipid transport enzymes in fat-induced insulin resistance ApoE -/- mice. METHOD: Eight male C57BL/6J mice were selected in the normal group (NF), 40 male ApoE -/- mice were fed for 16 weeks, divided into the model group (HF), the rosiglitazone group ( LGLT), the Jinlida low-dose group (JLDL), the Jinlida medium-dose group (JLDM), the Jinlida high-dose group (JLDH) and then orally given drugs for 8 weeks. The organization free fatty acids, BCA protein concentration determination methods were used to determine the skeletal muscle FFA content. The Real-time fluorescent quantitative reverse transcription PCR ( RT-PCR) and Western blot method were adopted to determine mRNA and protein expressions of mice fatty acids transposition enzyme (FAT/CD36), carnitine palm acyltransferase 1 (CPT1), peroxide proliferators-activated receptor α( PPAR α). RESULT: Jinlida could decrease fasting blood glucose (FBG), cholesterol (TC), triglyceride (TG), free fatty acid (FFA) and fasting insulin (FIns) and raise insulin sensitive index (ISI) in mice to varying degrees. It could also up-regulate mRNA and protein expressions of CPT1 and PPARα, and down-regulate mRNA and protein levels of FAT/CD36. CONCLUSION: Jinlida can improve fat-induced insulin resistance ApoE -/- in mice by adjusting the changes in expression of skeletal muscle lipid transport enzymes.

Polymer optical fiber twisted macro-bend coupling system for liquid level detection.

The liquid level detection principle of cladding mode frustrated total internal reflection (CMFTIR) effect is proposed. The significant enhancement of CMFTIR effect is realized through macro-bend coupling system in which the dark-field coupling phenomenon between two multimode polymer optic fibers is observed through experiment. Especially twisted macro-bend coupling structure (TMBCS) is adopted to achieve stable coupling of two naked POF. The testing result showed that the dark-filed forward coupling efficiency reached 2‰ and the extinction ratio of the liquid level probe reached 4.18 dB. Compared with existing optical fiber liquid level sensors, the TMBCS probe is simpler, robuster, and cheaper. In addition, the TMBCS has the potential for displacement or stress sensing.

Exosomes from Hypoxia-treated Mesenchymal Stem Cells: Promoting Neuroprotection in Ischemic Stroke Through miR-214-3p/PTEN Mechanism.

Stroke stands as the second leading cause of death globally, surpassed only by ischemic heart disease. It accounts for 9% of total worldwide deaths. Given the swiftly evolving landscape, medical professionals and researchers are devoting increased attention to identifying more effective and safer treatments. Recent years have witnessed a focus on exosomes derived from mesenchymal stem cells cultivated under hypoxic conditions, referred to as Hypo-Exo. These specialized exosomes contain an abundance of components that facilitate the restoration of ischemic tissue, surpassing the content found in normal exosomes. Despite advancements, the precise role of Hypo-Exo in cases of cerebral ischemia remains enigmatic. Therefore, this study was designed to shed light on the potential efficacy of Hypo-Exo in stroke treatment. Our investigations unveiled promising outcomes, as the administration of Hypo-Exo led to improved behavioral deficits and reduced infarct areas in mice affected by ischemic conditions. Notably, these positive effects were hindered when Hypo-Exo loaded with anti-miR-214-3p were introduced, implying that the neuroprotective attributes of Hypo-Exo are reliant on miR-214-3p. This conclusion was substantiated by the high levels of miR-214-3p detected within Hypo-Exo. Furthermore, our examination of the ischemic penumbra zone revealed a gradual and sustained escalation in PTEN expression, a phenomenon effectively countered by Hypo-Exo treatment. Collectively, our findings suggest the existence of a regulatory pathway centered on miR-214-3p within Hypo-Exo. This pathway exerts a downregulating influence on the PTEN/Akt signaling pathway, thereby contributing to the amelioration of neurological function subsequent to ischemia-reperfusion events.

[Protective effect of Qihuang Mingmu capsule on retina of diabetic mice and its impact on VEGF expression].

OBJECTIVE: To investigate the protective effect of Qihuang Mingmu capsule (QHMM) on retina of diabetic mice and its impact on VEGF expression. METHOD: Forty KK/Upj-Ay mice were randomly divided into the model group and high, middle and low dose QHMM (8.32, 4.16, 2.08 g x kg(-1)) groups. Additional 10 C57BL/6 mice were selected as the control group. Mice were orally administered for three months. Their general appearance, fasting blood-glucose (FBG) and glycosylated hemoglobin (HbA1c) were observed. Pathological changes of retina were observed by light microscope and electron microscope. The expressions of vascular endothelial growth factor (VEGF), growth factor receptors-1 (Flt-1) and growth factor receptors-2 (Flk-1) were examined by Real-time PCR (qPCR) and Western blot. RESULT: QHMM could ameliorate the symptoms of diabetic mice to varying degrees, decrease FBG and HbA1c, alleviate pathological lesions of retina and decrease the expressions of VEGF, Flt-1, Flk-1 mRNA and protein. CONCLUSION: QHMM has the protective effect on diabetic retinopathy of mice by inhibiting the expressions of VEGF, Flt-1 and Flk-1 and intervening VEGF-VEGFR signal transduction pathway.