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Ischemic heart disease (IHD) is a high-risk disease in the middle-aged and elderly population. The ischemic heart may be further damaged after reperfusion therapy with percutaneous coronary intervention (PCI) and other methods, namely, myocardial ischemia–reperfusion injury (MIRI), which further affects revascularization and hinders patient rehabilitation. Therefore, the investigation of new therapies against MIRI has drawn great global attention. Within the long history of the prevention and treatment of MIRI, traditional Chinese medicine (TCM) has increasingly been recognized by the scientific community for its multi-component and multi-target effects. These multi-target effects provide a conspicuous advantage to the anti-MIRI of TCM to overcome the shortcomings of single-component drugs, thereby pointing toward a novel avenue for the treatment of MIRI. However, very few reviews have summarized the currently available anti-MIRI of TCM. Therefore, a systematic data mining of TCM for protecting against MIRI will certainly accelerate the processes of drug discovery and help to identify safe candidates with synergistic formulations. The present review aims to describe TCM-based research in MIRI treatment through electronic retrieval of articles, patents, and ethnopharmacology documents. This review reported the progress of research on the active ingredients, efficacy, and underlying mechanism of anti-MIRI in TCM and TCM formulas, provided scientific support to the clinical use of TCM in the treatment of MIRI, and revealed the corresponding clinical significance and development prospects of TCM in treating MIRI.

Matrix metalloproteinases (MMPs), particularly MMP-2 and MMP-9, play an important role in ischemic injury to the heart, yet it is not known if these MMPs are involved in the injury that occurs to the transplant kidney. We therefore studied the pharmacologic protection of transplant kidneys during machine cold perfusion. Human kidney perfusates were analyzed for the presence of injury markers such as cytochrome c oxidase, lactate dehydrogenase, and neutrophil-gelatinase associated lipocalin (NGAL), and MMP-2 and MMP-9 were measured. The effects of MMP inhibitors MMP-2 siRNA and doxycycline were studied in an animal model of donation after circulatory determination of death (DCDD). Markers of injury were present in all analyzed perfusates, with higher levels seen in perfusates from human kidneys donated after controlled DCDD compared to brain death and in perfusate from kidneys with delayed graft function. When rat kidneys were perfused at 4°C for 22 hours with the addition of MMP inhibitors, this resulted in markedly reduced levels of MMP-2, MMP-9 and analyzed injury markers. Based on our study, MMPs are involved in preservation injury and the supplementation of preservation solution with MMP inhibitors is a potential novel strategy in protecting the transplant kidney from preservation injury.

Injury of myocardium during ischaemia/reperfusion (I/R) is a complex and multifactorial process involving uncontrolled protein phosphorylation, nitration/nitrosylation by increased production of nitric oxide and accelerated contractile protein degradation by matrix metalloproteinase‐2 (MMP‐2). It has been shown that simultaneous inhibition of MMP‐2 with doxycycline (Doxy) and myosin light chain kinase (MLCK) with ML‐7 at subthreshold concentrations protects the heart from contractile dysfunction triggered by I/R in a synergistic manner. In this study, we showed that additional co‐administration of nitric oxide synthase (NOS) inhibitor (1400W or L‐NAME) in subthreshold concentrations improves this synergistic protection in the model of hypoxia–reoxygenation (H‐R)‐induced contractile dysfunction of cardiomyocytes. Isolated cardiomyocytes were subjected to 3 min. of hypoxia and 20 min. of reoxygenation in the presence or absence of the inhibitor cocktails. Contractility of cardiomyocytes was expressed as myocyte peak shortening. Inhibition of MMP‐2 by Doxy (25–100 μM), MLCK by ML‐7 (0.5–5 μM) and NOS by L‐NAME (25–100 μM) or 1400W (25–100 μM) protected myocyte contractility after H‐R in a concentration‐dependent manner. Inhibition of these activities resulted in full recovery of cardiomyocyte contractility after H‐R at the level of highest single‐drug concentration. The combination of subthreshold concentrations of NOS, MMP‐2 and MLCK inhibitors fully protected cardiomyocyte contractility and MLC1 from degradation by MMP‐2. The observed protection with addition of L‐NAME or 1400W was better than previously reported combination of ML‐7 and Doxy. The results of this study suggest that addition of NOS inhibitor to the mixture of inhibitors is better strategy for protecting cardiomyocyte contractility.

Matrix metalloproteinases (MMPs) significantly contribute to ischemia reperfusion (I/R) injury, namely, by the degradation of contractile proteins. However, due to the experimental models adopted and lack of isoform specificity of MMP inhibitors, the cellular source and identity of the MMP(s) involved in I/R injury remain to be elucidated. Using isolated adult rat cardiomyocytes, subjected to chemically induced I/R-like injury, we show that specific inhibition of MMP-2 expression and activity using MMP-2 siRNA significantly protected cardiomyocyte contractility from I/R-like injury. This was also associated with increased expression of myosin light chains 1 and 2 (MLC1/2) in comparison to scramble siRNA transfection. Moreover, the positive effect of MMP-2 siRNA transfection on cardiomyocyte contractility and MLC1/2 expression levels was also observed under control conditions, suggesting an important additional role for MMP-2 in physiological sarcomeric protein turnover. This study clearly demonstrates that intracellular expression of MMP-2 plays a significant role in sarcomeric protein turnover, such as MLC1 and MLC2, under aerobic (physiological) conditions. In addition, this study identifies intracellular/autocrine, cardiomyocyte-produced MMP-2, rather than paracrine/extracellular, as responsible for the degradation of MLC1/2 and consequent contractile dysfunction in cardiomyocytes subjected to I/R injury.

Endothelial dysfunction, regarded as a key step in the pathophysiological course of diabetic vascular complications, is initiated and deteriorated by advanced glycation end products (AGEs). DL-3-n-butylphthalide (DL-NBP) has been proven to have protective effects on neurons and vascular endothelial cells against ischemic and anoxic damage. The aim of the present study was to investigate whether NBP is able to attenuate AGE-induced endothelial dysfunction in vitro, and also elucidate the possible underlying mechanism. An injury model of human umbilical vein endothelial cells (HUVECs) induced by AGEs (200 µg/ml) was established. The results demonstrated that pretreatment with NBP (1-100 µM) significantly increased HUVEC viability and inhibited the apoptosis induced by AGEs. In addition, AGEs stimulated the expression levels of the receptor for AGEs protein and the downstream protein nuclear factor-κB in HUVECs, which were inhibited by pretreatment with NBP. Furthermore, it significantly reduced reactive oxygen species generation and the level of the inflammatory cytokines, intercellular cell adhesion molecule-1 and monocyte chemotactic protein-1, in HUVECs mediated by AGEs. The current findings indicated that NBP attenuated AGE-induced endothelial dysfunction by ameliorating inflammation and oxidative stress responses.

CT could be used to evaluate abnormalities in the bowel wall, mesentery, adjacent structures, vasculature, and even the activity of Crohn disease (CD). To our knowledge, few direct comparisons of CD characterization using multidetector row CT with dynamic contrast enhancement, 3D imaging, CT angiography (CTA), and CT-enteroclysis (CT-E) on the same cohort of patients. The purpose of this study was to evaluate the diagnostic value of CD using multidetector helical CT with CT-E, dynamic contrast enhancement, 3D imaging, and CTA. Twenty-eight patients known or suspected CD underwent CT-E, dynamic contract enhancement, CTA, and 3D imaging. The multidetector CT series images were performed on eight-slice CT scanner. All the examinations were performed when water was used as an oral contrast starting 25 s after 140 mL of intravenous contrast agent was administered, followed by portal venous phase (60 s), and a 60-70 s delay, then sending 1.25-mm slices to the 3D workstation, CT angiograms and 3D images were reconstructed. All the images were reviewed to detect abnormalities of CD. The abnormalities of the bowel wall, mucosal and submucosal ulceration, prominent perienteric vasculature, sinus tracts or fistulae, abscess were evaluated. Crohn disease was diagnosed in 28 patients by CT images, and 54 inflammatory segments were revealed. In active inflammatory cases, the diseased bowel wall thickened and the enhancement of diseased bowel wall increased significantly in 34 inflammatory segments of 22 cases, the enhancement of diseased bowel wall increased significantly but without the wall thickened in three patients. Prominent vasculature was found in CTA and 3D images in 21 patients with active diseases. In 16 patients, the sharp interface between bowel and mesentery was lost and the attenuation of fat increased. Sinus tracts or fistulae were observed in eight patients, four of 28 patients demonstrated abscesses, all were active inflammatory patients. In three chronic inflammatory patients, normal bowel, bowel lumen stricture, and the normal enhancement of the wall were displayed. The abnormalities of CD and its complications can be identified by multidetector CT with CT-E, dynamic enhancement, CTA, and 3D imaging, and they are important methods in diagnosing CD. Complications of CD can be shown better when CT-E is performed.

A novel design of photonic crystal waveguide crossing based on multimode-interference (MMI) structure is proposed. Two structures of difference device lengths are simulated and studied. The proposed structures have high transmission efficiency for a wide bandwidth. The crosstalk is -26dB with device length of 12 lattice periods and -39dB with device length of 24 lattice periods. The plane wave expansion method and finite-difference time-domain method are used to calculate the modal dispersion curve and field propagation, respectively. The proposed MMI-based waveguide crossing has the potential to be practical in high-density optical integrated circuits.

High-boron steel is an important material used for thermal neutron shielding. The appropriate amount of added boron must be de- termined because excessive boron may deteriorate the steel＇s workability. A uniform microstructure can be formed by adding titanium to boron steel. In this study, casting and hot rolling were used to fabricate laminated high-boron steel plates whose cores contained 2.25wt% boron and 0wt%-7.9wt% titanium. The effects of titanium content and hot-rolling and heat-treatment processes on the microstructure and properties of the laminated plates were studied. The results indicated that the optimum titanium content was 5.7wt% when the boron content was 2.25wt%, and that the best overall properties were obtained after heat treatment at 1100℃ for 4 h. The tensile strength, yield strength, and elongation at the specified temperature and holding time were as high as 526.88 MPa, 219.36 MPa, and 29%, respectively.

Previous studies revealed that phthalate exposure could alter thyroid hormones during the last trimester of pregnancy. However, thyroid hormones are crucial for fetal development during the first trimester. We aimed to clarify the effect of phthalate exposure on thyroid hormones during early pregnancy. We recruited 97 pregnant women who were offered an amniocentesis during the early trimester from an obstetrics clinic in southern Taiwan from 2013 to 2014. After signing an informed consent form, we collected amniotic fluid and urine samples from pregnant women to analyze 11 metabolites, including mono-ethyl phthalate (MEP), mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP), mono-(2-ethylhexyl) phthalate (MEHP), mono-butyl phthalate (MnBP), of 9 phthalates using liquid chromatography/ tandem mass spectrometry. We collected blood samples from each subject to analyze serum thyroid hormones including thyroxine (T4), free T4, and thyroid-binding globulin (TBG). Three phthalate metabolites were discovered to be >80% in the urine samples of the pregnant women: MEP (88%), MnBP (81%) and MECPP (86%). Median MnBP and MECPP levels in pregnant Taiwanese women were 21.5 and 17.6 μg/g-creatinine, respectively, that decreased after the 2011 Taiwan DEHP scandal. Results of principal component analysis suggested two major sources (DEHP and other phthalates) of phthalates exposure in pregnant women. After adjusting for age, gestational age, TBG, urinary creatinine, and other phthalate metabolites, we found a significantly negative association between urinary MnBP levels and serum T4 (β = -5.41; p-value = 0.012; n = 97) in pregnant women using Bonferroni correction. We observed a potential change in the thyroid hormones of pregnant women during early pregnancy after DnBP exposure. Additional study is necessitated to clarify these associations.

Parkinson’s disease (PD) is a neurodegenerative disease, which is associated with mitochondrial dysfunction and abnormal protein accumulation. No treatment can stop or slow PD. Autophagy inhibits neuronal death by removing damaged mitochondria and abnormal protein aggregations. Celastrol is a triterpene with antioxidant and anti-inflammatory effects. Up until now, no reports have shown that celastrol improves PD motor symptoms. In this study, we used PD cell and mouse models to evaluate the therapeutic efficacy and mechanism of celastrol. In the substantia nigra, we found lower levels of autophagic activity in patients with sporadic PD as compared to healthy controls. In neurons, celastrol enhances autophagy, autophagosome biogenesis (Beclin 1↑, Ambra1↑, Vps34↑, Atg7↑, Atg12↑, and LC3-II↑), and mitophagy (PINK1↑, DJ-1↑, and LRRK2↓), and these might be associated with MPAK signaling pathways. In the PD cell model, celastrol reduces MPP+-induced dopaminergic neuronal death, mitochondrial membrane depolarization, and ATP reduction. In the PD mouse model, celastrol suppresses motor symptoms and neurodegeneration in the substantia nigra and striatum and enhances mitophagy (PINK1↑ and DJ-1↑) in the striatum. Using MPP+ to induce mitochondrial damage in neurons, we found celastrol controls mitochondrial quality by sequestering impaired mitochondria into autophagosomes for degradation. This is the first report to show that celastrol exerts neuroprotection in PD by activating mitophagy to degrade impaired mitochondria and further inhibit dopaminergic neuronal apoptosis. Celastrol may help to prevent and treat PD.