关键词：
Pulmonary fibrosis (PF);JAG1;Notch signaling;miR-30d;Primary normal human lung fibroblast (NHLF)
摘要：
Pulmonary fibrosis (PF) is a fibroproliferative disease which can finally end up fatal lung failure. PF is characterized by abnormal proliferation of fibroblast, dysregulated fibroblast differentiation to myofibroblast and disorganized collagen and extracellular matrix (ECM) production, deposition and degradation. JAG1/Notch signaling has been reported to play a key role in tissue fibrosis including PF. Herein, we confirmed the abnormal upregulation of JAG1 mRNA expression and protein levels in PF tissue specimens; JAG1 knockdown reduced TGF-beta 1-induced alpha-SMA and Collagen I protein levels. From the aspect of miRNA regulation, we searched for candidate miRNAs which might target JAG1 to inhibit its expression. Among the selected miRNAs, miR-30d expression was downregulated in PF tissues; miR-30d overexpression attenuated TGF-beta 1-induced primary normal human lung fibroblast (NHLF) proliferation, as well as alpha-SMA and Collagen I protein levels. Through directly binding to the 3'-UTR of JAG1, miR-30d significantly inhibited JAG1 mRNA expression and protein level. Furthermore, JAG1 overexpression partially reversed the effect of miR-30d on NHLF proliferation and alpha-SMA and Collagen I proteins upon TGF-beta 1 stimulation; miR-30d could suppress TGF-beta 1 function on NHLFs through blocking JAG1/Notch signaling. Rescuing miR-30d expression to suppress TGF-beta 1-induced activation of JAG1/Notch signaling may present a promising strategy for PF treatment.
作者：
Yang, Yi Jing;Peng, Jun;Ying, Deng;Peng, Qing Hua*
期刊：
Journal of Ophthalmology,2018年2018(5):3249064 ISSN：2090-004X
通讯作者：
Peng, Qing Hua
作者机构：
[Ying, Deng; Peng, Qing Hua; Yang, Yi Jing] Hunan Univ Chinese Med, Changsha 410208, Hunan, Peoples R China.;[Peng, Qing Hua; Peng, Jun] Hunan Univ Chinese Med, Affiliated Hosp 1, Dept Ophthalmol, Changsha 410007, Hunan, Peoples R China.
通讯机构：
[Peng, Qing Hua] H;Hunan Univ Chinese Med, Changsha 410208, Hunan, Peoples R China.;Hunan Univ Chinese Med, Affiliated Hosp 1, Dept Ophthalmol, Changsha 410007, Hunan, Peoples R China.
摘要：
Retinitis pigmentosa (RP) represents a clinically and genetically heterogeneous disease characterized by progressive photoreceptor loss. In recent years, research has been rarely made in blood flow affected in RP. The specific mechanism of blood flow affected in RP is not completely clear. A number of studies indicated that the decreased blood flow was related to RP. According to clinical observation and treatment experience, Chinese medicine considered that blood stasis runs throughout the RP disease progression, and the blood stasis corresponding to Chinese herbal medicine has a positive effect on the clinical treatment of RP. Therefore, we proposed that the decreased blood flow may participate in the lesion. In this article, we will review the findings on the decreased blood flow affected in RP from the perspective of modern medicine and Chinese medicine.
关键词：
Three-dimensional scanner;Soft tissue;Adult treatment;Extraction vs. nonextraction
摘要：
Objective: This study was performed to investigate buccal facial depth (BFD) changes after extraction and nonextraction orthodontic treatments in post-adolescent and adult female patients, and to explore possible influencing factors. Methods: Twelve and nine female patients were enrolled in the extraction and nonextraction groups, respectively. Changes in BFD in the defined buccal region and six transverse and two coronal measuring planes were measured after registering pretreatment and posttreatment three-dimensional facial scans. Changes in posterior dentoalveolar arch widths were also measured. Treatment duration, changes in body mass index (BMI), and cephalometric variables were compared between the groups. Results: BFD in the buccal region decreased by approximately 1.45 mm in the extraction group, but no significant change was observed in the nonextraction group. In the extraction group, the decrease in BFD was identical between the two coronal measuring planes, whereas this differed among the six transverse measuring planes. Posterior dentoalveolar arch widths decreased in the extraction group, whereas these increased at the second premolar level in the nonextraction group. The treatment duration of the extraction group was twice that of the nonextraction group. No differences were found in BMI and Frankfort horizontal-mandibular plane angle changes between the groups. BFD changes in the buccal region moderately correlated with treatment duration and dental arch width change. Conclusions: BFD decreased in adult female patients undergoing extraction, and this may be influenced by the long treatment duration and constriction of dentoalveolar arch width. However, nonextraction treatment did not significantly alter BFD.
摘要：
Aims: Neutrophil extracellular traps (NETs) comprise a unique form of non-apoptotic cell death exhibited by neutrophils, which occurs in a stepwise process termed NETosis. It has been postulated that NETosis plays an important role in the pathogenesis of autoimmune disorders. The aim of this study was to evaluate serum levels of NET remnants in patients with rheumatoid arthritis (RA), as well as potential associations between NET remnants and indicators of RA. Methods: Serum levels of myeloperoxidase (MPO)-DNA complexes (NET remnants) were examined in 74 RA patients and 50 healthy controls using a modified enzyme-linked immunosorbent assay. Associations between the levels of these complexes and indicators of RA were then statistically evaluated. Results: RA patients exhibited significantly higher levels of MPO-DNA complexes than the healthy controls, and these levels were associated with increased neutrophil counts and positivity for rheumatoid factor (RF) and anti-citrullinated protein/peptide antibodies (ACPA). Among the 63 ACPA-positive RA patients examined, those with ACPA titers > 1600 U/mL showed significantly increased MPO-DNA levels. Receiver operating characteristic analysis determined that the area under the curve for all 74 RA patients was 0.798, with a sensitivity of 91.9% and a specificity of 56.0%, while that for the ACPA-negative patients was 0.891, with a sensitivity and specificity of 81.8% and 84.0%, respectively. Conclusions: The results of this study suggest that the disease status of RA is associated with increased NETosis. In particular, evaluation of serum MPO-DNA levels may comprise a useful complementary tool for discriminating RA patients from healthy individuals.
摘要：
The disorder of lipid metabolism is pathologically linked to hyperlipidemia, lipid storage disease, obesity and other related diseases. Intriguingly, recent studies have revealed that lipid metabolism disorders play an important role in carcinogenesis and development as well, since they cause abnormal expression of various genes, proteins, and dysregulation of cytokines and signaling pathways. More importantly, lipid-lowering drugs and anti-lipid per-oxidation treatment have been showing their advantages in clinic, in comparison with other anti-cancer drugs with high toxicity. Thus, further elucidation of molecular mechanism between lipid metabolism and cancer is essential in developing novel diagnostic biomarkers and therapeutic targets of human cancers.
作者机构：
[Zhang, Zhanwei; Yu, Jianbai] Hunan Univ Chinese Med, Affiliated Hosp 1, Dept Neurosurg, Changsha 410007, Hunan, Peoples R China.
通讯机构：
[Yu, Jianbai] H;Hunan Univ Chinese Med, Affiliated Hosp 1, Dept Neurosurg, Changsha 410007, Hunan, Peoples R China.
关键词：
Cerebral IR injury;NR4A1;Mitophagy;MAPK-ERK-CREB signaling pathway
摘要：
Mitochondrial dysfunction has been acknowledged as the key pathogenic mechanism in cerebral ischemia-reperfusion (IR) injury. Mitophagy is the protective system used to sustain mitochondrial homeostasis. However, the upstream regulator of mitophagy in response to brain IR injury is not completely understood. Nuclear receptor subfamily 4 group A member 1 (NR4A1) has been found to be associated with mitochondrial protection in a number of diseases. The aim of our study is to explore the functional role of NR4A1 in cerebral IR injury, with a particular focus on its influence on mitophagy. Wild-type mice and NR4A1-knockout mice were used to generate cerebral IR injury in vivo. Mitochondrial function and mitophagy were detected via immunofluorescence assays and western blotting. Cellular apoptosis was determined via MTT assays, caspase-3 activity and western blotting. Our data revealed that NR4A1 was significantly increased in the reperfused brain tissues. Genetic ablation of NR4A1 reduced the cerebral infarction area and repressed neuronal apoptosis. The functional study demonstrated that NR4A1 modulated cerebral IR injury by inducing mitochondrial damage. Higher NR4A1 promoted mitochondrial potential reduction, evoked cellular oxidative stress, interrupted ATP generation, and initiated caspase-9-dependent apoptosis. Mechanistically, NR4A1 induced mitochondrial damage by disrupting Mfn2-mediated mitophagy. Knockdown of NR4A1 elevated Mfn2 expression and therefore reversed mitophagic activity, sending a prosurvival signal for mitochondria in the setting of cerebral IR injury. Further, we demonstrated that NR4A1 modulated Mfn2 expression via the MAPK-ERK-CREB signaling pathway. Blockade of the ERK pathway could abrogate the permissive effect of NR4A1 deletion on mitophagic activation, contributing to neuronal mitochondrial apoptosis. Overall, our results demonstrate that the pathogenesis of cerebral IR injury is closely associated with a drop in protective mitophagy due to increased NR4A1 through the MAPK-ERK-CREB signaling pathway.
作者机构：
[Liang, Ri-xin; Li, Qiu-yue; Guo, Qiu-yan; Zhang, Yi; Li, De-feng; Zhang, Yan-qiong; Tang, Shi-huan; Yang, Hong-jun; Xu, Hai-yu] China Acad Chinese Med Sci, Inst Chinese Mat Med, Beijing 100700, Peoples R China.;[Ren, Wei-qiong] Hunan Univ Tradit Chinese Med, Affiliated Hosp 1, Changsha 410007, Hunan, Peoples R China.;[Wang, Song-song] Univ Macau, Inst Chinese Med Sci, State Key Lab Qual Res Chinese Med, Macau 999078, Peoples R China.
通讯机构：
[Xu, Hai-yu] C;China Acad Chinese Med Sci, Inst Chinese Mat Med, Beijing 100700, Peoples R China.
关键词：
traditional Chinese medicine;Guanxinjing capsule;coronary heart disease;depression;integrative pharmacology;in silico ADME prediction;target prediction;network analysis
摘要：
Guanxinjing capsules (GXJCs) are used in traditional Chinese medicine as a common therapy for coronary heart disease (CHD) complicated with depression. In this study, we aimed to identify the main active constituents in GXJCs and to investigate the mechanisms of GXJC action on CHD complicated with depression. The chemical constituent profile of the GXJC was identified by UHPLC-LTQ-Orbitrap assay, and oral bioavailability was evaluated to screen the GXJC drug-like chemical constituents. A total of 16 GXJC drug-like chemical constituents were identified. Then, putative targets of the GXJC drug-like chemical constituents were predicted using MedChem Studio, with 870 genes found to be the putative targets of these molecules. After that, a GXJC putative target-known CHD/depression therapeutic target network was constructed, and four topological features, including degree, betweenness, closeness and K-coreness, were calculated. According to the topological feature values of the GXJC putative targets, 14 main active constituents were identified because their corresponding putative targets had topological importance in the GXJC putative target-known CHD/depression therapeutic target network, which were defined as the candidate targets of GXJC against CHD complicated with depression. Functionally, these candidate targets were significantly involved in several CHD/depression-related pathways, including repairing pathological vascular changes, reducing platelet aggregation and inflammation, and affecting patient depression. This study identified a list of main active constituents of GXJC acting on CHD complicated with depression using an integrative pharmacology-based approach that combined active chemical constituent identification, drug target prediction and network analysis. This method may offer an efficient way to understand the pharmacological mechanisms of traditional Chinese medicine prescriptions.
摘要：
Abdominal aortic aneurysm (AAA) is a vascular disease with high mortality. Because of the lack of effective medications to stop or reverse the progression of AAA, surgical operation has become the most predominant recommendation of treatment for patients. There are many potential mechanisms, including inflammation, smooth muscle cell apoptosis, extracellular matrix degradation, oxidative stress, and so on, involving in AAA pathogenesis. According to those mechanisms, some potential therapeutic drugs have been proposed and tested in animal models and even in clinical trials. This review focuses on recent advances in both pathogenic mechanisms and potential pharmacologic therapies of AAA.
作者：
Long, Da;Kanan, Yogita;Shen, Jikui;Hackett, Sean F.;Liu, Yuanyuan;...
期刊：
JCI insight,2018年3(10) ISSN：2379-3708
通讯作者：
Campochiaro, Peter A.
作者机构：
[Long, Da] Hunan Univ Chinese Med, Hosp 1, Dept Ophthalmol, Changsha, Hunan, Peoples R China.;Johns Hopkins Univ, Sch Med, Dept Ophthalmol, Baltimore, MD 21205 USA.;Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA.;[Liu, Yuanyuan] Tianjin Med Univ, Gen Hosp, Dept Ophthalmol, Tianjin, Peoples R China.;[Campochiaro, Peter A.] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, 815 Maumenee,600 N Wolfe St, Baltimore, MD 21205 USA.
通讯机构：
[Campochiaro, Peter A.] J;Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, 815 Maumenee,600 N Wolfe St, Baltimore, MD 21205 USA.
关键词：
Angiogenesis;Drug therapy;Ophthalmology
摘要：
Intraocular injections of VEGF-neutralizing proteins provide tremendous benefits in patients with choroidal neovascularization (NV) due to age-related macular degeneration (AMD), but during treatment some patients develop retinal atrophy. Suggesting that VEGF is a survival factor for retinal neurons, a clinical trial group attributed retinal atrophy to VEGF suppression and cautioned against frequent anti-VEGF injections. This recommendation may contribute to poor outcomes in clinical practice from insufficient treatment. Patients with type 3 choroidal NV have particularly high risk of retinal atrophy, an unexplained observation. Herein we show in mouse models that VEGF signaling does not contribute to photoreceptor survival and functioning: (a) neutralization of VEGFR2 strongly suppresses choroidal NV without compromising photoreceptor function or survival; (b) VEGF does not slow loss of photoreceptor function or death in mice with inherited retinal degeneration, and there is no exacerbation by VEGF suppression; and (c) mice with type 3 choroidal NV develop retinal atrophy due to oxidative damage with no contribution from VEGF suppression. Intraocular injections of VEGF-neutralizing proteins, a highly effective treatment in patients with neovascular AMD, should not be withheld or reduced due to concern that they may contribute to long-term visual loss from retinal atrophy.
