Galectin-3 inhibition alleviated LPS-induced periodontal inflammation in gingival fibroblasts and experimental periodontitis mice.

OBJECTIVES: Clinical studies have confirmed that galectin-3 (Gal-3) levels are significantly elevated in periodontitis patients. The present study aimed to explore the effects of Gal-3 inhibition on periodontal inflammation in vitro and in vivo. METHODS: Human gingival fibroblasts (HGFs) with or without Gal-3 knockdown were stimulated by lipopolysaccharide (LPS), and a ligation-induced mouse periodontitis model treated with a Gal-3 inhibitor was established. Hematoxylin-eosin (H&E) and immunohistochemistry (IHC) staining were used to evaluate Gal-3 levels in gingival tissues. Quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) were used to detect Gal-3, interleukin (IL)-6, IL-8, and C-C motif ligand 2 (CCL2) expression. Immunofluorescence and western blotting were used to detect NF-κB and ERK signaling pathway activation. Micro-computed tomography was used to analyse the degree of bone loss. RESULTS: Gal-3 was significantly up-regulated in inflamed gingival tissues and LPS-induced HGFs. Gal-3 knockdown markedly decreased LPS-induced IL-6, IL-8, and CCL2 expression and blocked NF-κB and ERK signaling pathway activation in HGFs. In the mouse periodontitis model, Gal-3 inhibition significantly alleviated IL-1ß and IL-6 infiltration in gingival tissue and mitigated periodontal bone loss. CONCLUSIONS: Gal-3 inhibition notably alleviated periodontal inflammation partly through blocking NF-κB and ERK signaling pathway activation.

Silver Metal-Organic Framework Derived N-Doped Carbon Nanofibers for CO2 Conversion into ß-Oxopropylcarbamates.

Developing efficient heterogeneous catalysts for chemical fixation of CO2 to produce high-value-added chemicals under mild conditions is highly desired but still challenging. Herein, we first reported an approach to prepare a novel catalyst (Ag@NCNFs), featuring Ag nanoparticles (NPs) embedded within porous nitrogen-doped carbon nanofibers (NCNFs), via growing a Ag metal-organic framework on one-dimensional electrospun nanofibers followed by pyrolysis. Benefiting from the abundant nitrogen species and porous structure, Ag NPs is well dispersed in the obtained Ag@NCNFs. Catalytic studies indicated that Ag@NCNFs exhibited excellent catalytic activity for the three-component coupling reaction of CO2, secondary amines, and propargylic alcohols to generate ß-oxopropylcarbamates under mild conditions with a turnover number (TON) of 16.2, and it can be recycled and reused at least 5 times without an obvious decline in catalytic activity. The reaction mechanism was clearly clarified by FTIR, NMR, 13C isotope labeling, control experiments, and density functional theory calculations. The results suggest that Ag@NCNFs and 1,8-diazabicyclo[5.4.0]undec-7-ene can synergistically activate propargylic alcohol to react with CO2, and then the generated α-alkylidene cyclic carbonate was invaded by secondary amine to produce ß-oxopropylcarbamate. Importantly, to the best of our knowledge, this is the first experimental and theoretical investigation on this reaction.

Physiological ß-amyloid clearance by the liver and its therapeutic potential for Alzheimer's disease.

Cerebral amyloid-ß (Aß) accumulation due to impaired Aß clearance is a pivotal event in the pathogenesis of Alzheimer's disease (AD). Considerable brain-derived Aß is cleared via transporting to the periphery. The liver is the largest organ responsible for the clearance of metabolites in the periphery. Whether the liver physiologically clears circulating Aß and its therapeutic potential for AD remains unclear. Here, we found that about 13.9% of Aß42 and 8.9% of Aß40 were removed from the blood when flowing through the liver, and this capacity was decreased with Aß receptor LRP-1 expression down-regulated in hepatocytes in the aged animals. Partial blockage of hepatic blood flow increased Aß levels in both blood and brain interstitial fluid. The chronic decline in hepatic Aß clearance via LRP-1 knockdown specific in hepatocytes aggravated cerebral Aß burden and cognitive deficits, while enhancing hepatic Aß clearance via LRP-1 overexpression attenuated cerebral Aß deposition and cognitive impairments in APP/PS1 mice. Our findings demonstrate that the liver physiologically clears blood Aß and regulates brain Aß levels, suggesting that a decline of hepatic Aß clearance during aging could be involved in AD development, and hepatic Aß clearance is a novel therapeutic approach for AD.

Long noncoding RNA NEAT1 promotes cardiac fibrosis in heart failure through increased recruitment of EZH2 to the Smad7 promoter region.

Cardiac fibrosis, a well-known major pathological process that ultimately leads to heart failure, has attracted increasing attention and focus in recent years. A large amount of research indicates that long noncoding RNAs (lncRNAs) play an important role in cardiac fibrosis, but little is known about the specific function and mechanism of the lncRNA NEAT1 in the progression of cardiac fibrosis to heart failure. In the present study, we have demonstrated that the lncRNA NEAT1 is upregulated in patients with heart failure. Similarly, the expression of Neat1 was also increased in the left ventricular tissue of transverse aortic constriction (TAC) surgery mice and cardiac fibroblasts treated with TGF-ß1. Further, gain-of-function and loss-of-function experiments showed that silencing of Neat1 attenuated cardiac fibrosis, while overexpression of Neat1 with adenovirus significantly aggravated the in vitro progression of fibrosis. With regard to the underlying mechanism, our experiments showed that Neat1 recruited EZH2 to the promoter region of Smad7 through physical binding of EZH2 to the promoter region, as a result of which Smad7 expression was inhibited and the progression of cardiac fibrosis was ultimately exacerbated. We found that the introduction of shNeat1 carried by adeno-associated virus-9 significantly ameliorated cardiac fibrosis and dysfunction caused by TAC surgery in mice. Overall, our study findings demonstrate that the lncRNA Neat1 accelerates the progression of cardiac fibrosis and dysfunction by recruiting EZH2 to suppress Smad7 expression. Thus, NEAT1 may serve as a target for the treatment of cardiac fibrosis.

Blood cell-produced amyloid-ß induces cerebral Alzheimer-type pathologies and behavioral deficits.

It is traditionally believed that cerebral amyloid-beta (Aß) deposits are derived from the brain itself in Alzheimer's disease (AD). Peripheral cells such as blood cells also produce Aß. The role of peripherally produced Aß in the pathogenesis of AD remains unknown. In this study, we established a bone marrow transplantation model to investigate the contribution of blood cell-produced Aß to AD pathogenesis. We found that bone marrow cells (BMCs) transplanted from APPswe/PS1dE9 transgenic mice into wild-type (Wt) mice at 3 months of age continuously expressed human Aß in the blood, and caused AD phenotypes including Aß plaques, cerebral amyloid angiopathy (CAA), tau hyperphosphorylation, neuronal degeneration, neuroinflammation, and behavioral deficits in the Wt recipient mice at 12 months after transplantation. Bone marrow reconstitution in APPswe/PS1dE9 mice with Wt-BMCs at 3 months of age reduced blood Aß levels, and alleviated brain Aß burden, neuronal degeneration, neuroinflammation, and behavioral deficits in the AD model mice at 12 months after transplantation. Our study demonstrated that blood cell-produced Aß plays a significant role in AD pathogenesis, and the elimination of peripheral production of Aß can decrease brain Aß deposition and represents a novel therapeutic approach for AD.

Physiological clearance of amyloid-beta by the kidney and its therapeutic potential for Alzheimer's disease.

Amyloid-ß (Aß) accumulation in the brain is a pivotal event in the pathogenesis of Alzheimer's disease (AD), and its clearance from the brain is impaired in sporadic AD. Previous studies suggest that approximately half of the Aß produced in the brain is cleared by transport into the periphery. However, the mechanism and pathophysiological significance of peripheral Aß clearance remain largely unknown. The kidney is thought to be responsible for Aß clearance, but direct evidence is lacking. In this study, we investigated the impact of unilateral nephrectomy on the dynamic changes in Aß in the blood and brain in both humans and animals and on behavioural deficits and AD pathologies in animals. Furthermore, the therapeutic effects of the diuretic furosemide on Aß clearance via the kidney were assessed. We detected Aß in the kidneys and urine of both humans and animals and found that the Aß level in the blood of the renal artery was higher than that in the blood of the renal vein. Unilateral nephrectomy increased brain Aß deposition; aggravated AD pathologies, including Tau hyperphosphorylation, glial activation, neuroinflammation, and neuronal loss; and aggravated cognitive deficits in APP/PS1 mice. In addition, chronic furosemide treatment reduced blood and brain Aß levels and attenuated AD pathologies and cognitive deficits in APP/PS1 mice. Our findings demonstrate that the kidney physiologically clears Aß from the blood, suggesting that facilitation of Aß clearance via the kidney represents a novel potential therapeutic approach for AD.

Highly Efficient Conversion of Propargylic Alcohols and Propargylic Amines with CO2 Activated by Noble-Metal-Free Catalyst Cu2 O@ZIF-8.

The cyclization reactions of propargylic alcohols and propargylic amines with CO2 are important in industrial applications, but it was a great challenge that non-noble-metal catalysts catalyzed both reactions under mild conditions. Herein, the catalyst Cu2 O@ZIF-8 was prepared by encapsulating Cu2 O nanoparticles into robust ZIF-8, and it can effectively catalyze the cyclization of both propargylic alcohols and propargylic amines with CO2 into valuable α-alkylidene cyclic carbonates and oxazolidinones with turnover numbers (TONs) of 12.1 and 19.6, which can be recycled at least five times. The mechanisms were further uncovered by NMR, FTIR, 13 C isotope-labeling experiments and DFT calculations, in which Cu2 O and DBU can synergistically activate the C≡C bond and the hydroxy/amino group of substrates. Importantly, it is the first example of a noble-metal-free catalyst that can catalyze both propargylic alcohols and propargylic amines with CO2 simultaneously.

Rapid Synthesis of Silk-Like Polymers Facilitated by Microwave Irradiation and Click Chemistry.

Silk is a natural fiber that surpasses most man-made polymers in its combination of strength and toughness. Silk fibroin, the primary protein component of silk, can be synthetically mimicked by a linear copolymer with alternating rigid and soft segments. Strategies for chemical synthesis of such silk-like polymers have persistently resulted in poor sequence control, long reaction times, and low molecular weights. Here, we present a two-stage approach for rapidly synthesizing silk-like polymers with precisely defined rigid blocks. This approach utilizes solid-phase peptide synthesis to create uniform oligoalanine "prepolymers", followed by microwave-assisted step-growth polymerization with bifunctional poly(ethylene glycol). Multiple coupling chemistries and reaction conditions were explored, with microwave-assisted click chemistry yielding polymers with Mw ∼ 14 kg/mol in less than 20 min. These polymers formed antiparallel ß-sheets and nanofibers, which is consistent with the structure of natural silk fibroin. Thus, our strategy demonstrates a promising modular approach for synthesizing silk-like polymers.

Non-Noble-Metal Metal-Organic-Framework-Catalyzed Carboxylative Cyclization of Propargylic Amines with Atmospheric Carbon Dioxide under Ambient Conditions.

The coupling reaction of propargylic amines and carbon dioxide (CO2) to synthesize 2-oxazolidinones is an important reaction in industrial production, and yet harsh reaction conditions and noble-metal catalysts are often required to achieve high product yields. Herein, one novel noble-metal-free three-dimensional framework, [Mg3Cu2I2(IN)4(HCOO)2(DEF)4]n (1), assembled by magnesium and copper clusters was synthesized and applied to this reaction. Compound 1 displays excellent solvent stability. Importantly, 1, acting as heterogeneous catalyst, can highly catalyze the cyclization of propargylic amines with CO2 under atmospheric pressure at room temperature, which can be recycled at least five times without an obvious decrease of the catalytic activity. NMR spectroscopy, coupled with 13C-isotope- and deuterium-labeling experiments, clearly clarifies the mechanism of this catalytic system: CO2 was successfully captured and converted to the product of 2-oxazolidinones, the C≡C bond of propargylic amines can be effectively activated by 1, and proton transfer was involved in the reaction process. Density functional theory calculations are further conducted to uncover the reaction path and the crucial role of compound 1 during the reaction.

A Porous Copper-Organic Framework Assembled by [Cu12] Nanocages: Highly Efficient CO2 Capture and Chemical Fixation and Theoretical DFT Calculations.

A new porous copper-organic framework assembled from 12-nuclear [Cu12] nanocages {[Cu2(L4-)(H2O)2]·4DMA·2H2O}n (1) (H4L = 5,5'-(butane-1,4-diyl)-bis(oxy)-diisophthalic acid) was successfully prepared and structurally characterized. Compound 1 feathering of a 3D framework with two types of 1D nanotubular channels and a large specific surface area can effectively enrich various harmful dyes. Additionally, due to the carbon dioxide (CO2) interactions with open Cu(II) sites and the electron-rich ether oxygen atoms of ligand in 1, it exhibits a highly selective CO2 uptake. Interestingly, 1 can effectively catalyze the cycloaddition reaction of CO2 with various epoxides under mild conditions, which is ascribed to the Lewis acid Cu(II) sites in the framework of 1. Importantly, 1 acting as a heterogeneous catalyst can be recycled at least 10 times without an obvious loss of catalytic activity, and the CO2 cycloaddition mechanism was further uncovered by density functional theory (DFT) calculations. This study can greatly enrich the MOF catalysts system of CO2 conversion and also provide a valuable guidance for the design of efficient MOFs catalysts.

[Protective effect of ginsenoside Rg_1 on hypoxia/reoxygenation injury and its mechanism].

This project aimed to explore the protective effect of ginsenoside Rg_1 on hypoxia/reoxygenation(H/R)-induced H9 c2 cardiomyocyte injury and its underlying signaling pathway. The H/R model of H9 c2 cardiomyocytes was established and then the cells were divided into different treatment groups. CCK-8(cell counting kit-8) was used to detect the activity of cardiomyocytes; Brdu assay was used to detect the proliferation of H9 c2 cells; the caspase-3 activity was tested, and then the protein expression was assessed by Western blot. Flow cytometry was used to evaluate the apoptosis level of cardiomyocytes. Ginsenoside Rg_1 inhibited H/R-induced cardiomyocyte apoptosis and caspase-3 activity, promoted nuclear transcription of nuclear factor erythroid-2 related factor 2(Nrf2), and enhanced the expression of the downstream heme oxygenase-1(HO-1). Ginsenoside Rg_1 could increase Nrf2 nuclear transcription and HO-1 expression with the increase of concentration(10, 20, 40, 60 µmol·L~(-1)). However, the protective effect of ginsenoside Rg_1 on cardiomyocytes was significantly weakened after the transfection of Nrf2-siRNA. Ginsenoside Rg_1 could protect cardiomyocytes by activating the Nrf2/HO-1 pathway.

Recovery of High Value-Added Nutrients from Fruit and Vegetable Industrial Wastewater.

The industrial processing water of fruit and vegetables has raised serious environmental concerns due to the presence of many important bioactive compounds being disposed in the wastewater. Bioactive compounds have great potential for the food industry to optimize their process and to recover these compounds in order to develop value-added products and to reduce environmental impacts. However, to achieve this goal, some challenges need to be addressed such as safety assurance, technology request, product regulations, cost effectiveness, and customer factors. Therefore, this review aims to summarize the recent advances of bioactive compounds recovery and the current challenges in wastewater from fruit and vegetable processing industry, including fruit and beverage, soybean by-products, starch and edible oil industry. Moreover, future direction for novel and green technology of bioactive compounds recovery are discussed, and a prospect of bioactive compounds reuse and sustainable development is proposed.

CAl3X (X = B/Al/Ga/In/Tl) with 16 valence electrons: can planar tetracoordinate carbon be stable?

As a perpetual chemical curiosity, planar tetracoordinate carbon (ptC) that violates the traditional tetrahedral carbon (thC) has made enormous achievements. In particular, the 18-valence-electron (18ve) counting rule has been found to be very effective in predicting ptC structures, as in CX42- (X = Al/Ga/In/Tl). By contrast, the corresponding neutral CX4 with 16ve each takes the thC form like methane. Herein, we report a mono-substituted neutral 16ve-CAl3X (X = Al/Ga/In/Tl). Our theoretical results showed that the competition between thC and ptC can be well tuned upon variation of X, and for X = In and Tl, the ptC structure becomes isoenergetic to and even more stable than thC, respectively. Thus, a low-lying ptC can be achieved in the 16ve-CAl3X set without acquiring additional electrons. This unintuitive result can be ascribed to the increased energetic preference of the ionic sub-structure [CAl3-]X+ from X = Al to Tl. We thus predict the first penta-atomic ptC species with 16ve, and the ionic strategy presented in this work is expected to promote novel designs of ptC molecules.

Notch Signaling in Endothelial Cells: Is It the Therapeutic Target for Vascular Neointimal Hyperplasia?

Blood vessels respond to injury through a healing process that includes neointimal hyperplasia. The vascular endothelium is a monolayer of cells that separates the outer vascular wall from the inner circulating blood. The disruption and exposure of endothelial cells (ECs) to subintimal components initiate the neointimal formation. ECs not only act as a highly selective barrier to prevent early pathological changes of neointimal hyperplasia, but also synthesize and release molecules to maintain vascular homeostasis. After vascular injury, ECs exhibit varied responses, including proliferation, regeneration, apoptosis, phenotypic switching, interacting with other cells by direct contact or secreted molecules and the change of barrier function. This brief review presents the functional role of the evolutionarily-conserved Notch pathway in neointimal hyperplasia, notably by regulating endothelial cell functions (proliferation, regeneration, apoptosis, differentiation, cell-cell interaction). Understanding endothelial cell biology should help us define methods to prompt cell proliferation, prevent cell apoptosis and dysfunction, block neointimal hyperplasia and vessel narrowing.

[Association of health literacy with health management among diabetics].

OBJECTIVE: To understand status of health literacy among diabetics and their health management behaviors, and analyze the relationship of health literacy and health management. METHODS: A two-staged cluster randomized sampling method was used to investigate 1 130 diabetics in Beijing, Ningbo and Xiamen from October to November in 2012. All participants should be diagnosed by primary hospital and above and have lived in the community over six months. Diabetic patients who indicated that they had severely impaired vision or cognitive disorder, or had severe physical deterioration, or did not live in the address provided were excluded. A total of 1 130 questionnaires were sent out and 1 083 eligible questionnaires were taken back, accounting for 96.87%. Multivariate logistic regression was adopted to analyze the association between health literacy and health management behaviors and blood glucose level. RESULTS: Among those participants, 47.7% (517) were men, 52.3% (566) were women, the age was (67.0 ± 9.5). According to diabetes health literacy scores, 73.7% (798/1 083) of them were classified as poor health literacy and 26.1% (283/1 083) as essential health literacy. Health literacy was associated with health management behaviors independently, demonstrating that the probability of utilizing health education, free physical examination, lifestyle guidance, monitoring blood glucose on their own, measuring blood glucose more than once a week and taking hypoglycemic agent regularly among diabetics with essential health literacy were 1.40 (95%CI:1.03-1.91), 1.65 (95%CI: 1.19-2.28), 2.70 (95%CI:1.98-3.69), 2.05 (95%CI:1.34-3.15), 2.56 (95%CI:1.85-3.56) , 1.48 (95%CI:1.07-2.06) times of those in diabetics with poor health literacy (P < 0.05). CONCLUSION: Health literacy may affect health management behaviors among diabetics. More activities targeted on diabetics with low health literacy were suggested to improve their' health literacy and their skills about diabetes mellitus management.

Modified Si Miao Powder granules alleviates osteoarthritis progression by regulating M1/M2 polarization of macrophage through NF-κB signaling pathway.

Background: Osteoarthritis (OA) is a chronic degenerative disease mainly characterized by cartilage damage and synovial inflammation. Si Miao Powder, an herbal formula, was recorded in ancient Chinese medicine prescription with excellent anti-inflammatory properties. Based on the classical formula, the modified Si Miao Powder (MSMP) was developed with the addition of two commonly Chinese orthopedic herbs, which had the efficacy of strengthening the therapeutic effect for OA. Methods: In the in vivo experiments, thirty-six 8-week-old male C57BL/6 mice were randomly divided into six groups: sham group, OA group, celecoxib group, low-MSMP group, middle-MSMP group, and high-MSMP group. OA mice were constructed by destabilization of medial meniscus (DMM) and treated with MSMP granules or celecoxib by gavage. The effects of MSMP on cartilage, synovitis and inflammatory factor of serum were tested. For in vitro experiments, control serum and MSMP-containing serum were prepared from twenty-five C57BL/6 mice. Macrophages (RAW264.7 cells) were induced by lipopolysaccharide (LPS) and then treated with MSMP-containing serum. The expression of inflammatory factors and the change of the NF-κB pathway were tested. Results: In vivo, celecoxib and MSMP alleviated OA progression in the treated groups compared with OA group. The damage was partly recovered in cartilage, the synovial inflammatory were reduced in synovium, and the concentrations of IL-6 and TNF-α were reduced and the expression of IL-10 was increased in serum. The function of the middle MSMP was most effective for OA treatment. The results of in vitro experiments showed that compared with the LPS group, the MSMP-containing serum significantly reduced the expression levels of pro-inflammatory (M1-type) factors, such as CD86, iNOS, TNF-α and IL-6, and promoted the expression levels of anti-inflammatory (M2-type) factors, such as Arg1 and IL-10. The MSMP-containing serum further inhibited NF-κB signaling pathway after LPS induction. Conclusion: The study demonstrated that MSMP alleviated OA progression in mice and MSMP-containing serum modulated macrophage M1/M2 phenotype by inhibiting the NF-κB signaling pathway. Our study provided experimental evidence and therapeutic targets of MSMP for OA treatment.

Highly Efficient Conversion of Aziridines and CO2 Catalyzed by Microporous [Cu12] Nanocages.

The conversion of CO2 as a C1 source into value-added products is an attractive alternative in view of the green synthesis. Among the reported approaches, the cyclization reaction of aziridines with CO2 is of great significance since the generated N-containing cyclic skeletons are extensively found in pharmaceutical chemistry and industrial production. However, a low turnover number (TON) and homogeneous catalysts are often involved in this catalytic system. Herein, one novel copper-organic framework {[Cu2(L4-)(H2O)2]·3DMF·2H2O}n (1) (H4L = 2'-fluoro-[1,1':4',1″-Terphenyl]-3,3″,5,5″-tetracarboxylic acid) assembled by nanosized [Cu12] cages was successfully synthesized and structurally characterized, which exhibits high CO2/N2 selectivity due to the strong interactions between CO2 and open Cu(II) sites and ligands in the framework. Catalytic investigations suggest that 1 as a heterogeneous catalyst can effectively catalyze the cyclization of aziridines with CO2, and the TON can reach a record value of 90.5. Importantly, 1 displays excellent chemical stability, which can be recycled at least five times. The combination explorations of nuclear magnetic resonance (NMR), 13C-isotope labeling experiments, and density functional theory (DFT) clearly uncover the mechanism of this aziridine/CO2 coupling reaction system, in which 1 and tetrabutylammonium bromide (TBAB) can highly activate the substrate molecule, and the synergistic catalytic effect between them can greatly reduce the reaction energy barrier from 51.7 to 36.2 kcal/mol.

Elevated Levels of Naturally-Occurring Autoantibodies Against the Extracellular Domain of p75NTR Aggravate the Pathology of Alzheimer's Disease.

The extracellular domain (p75ECD) of p75 neurotrophin receptor (p75NTR) antagonizes Aß neurotoxicity and promotes Aß clearance in Alzheimer's disease (AD). The impaired shedding of p75ECD is a key pathological process in AD, but its regulatory mechanism is largely unknown. This study was designed to investigate the presence and alterations of naturally-occurring autoantibodies against p75ECD (p75ECD-NAbs) in AD patients and their effects on AD pathology. We found that the cerebrospinal fluid (CSF) level of p75ECD-NAbs was increased in AD, and negatively associated with the CSF levels of p75ECD. Transgenic AD mice actively immunized with p75ECD showed a lower level of p75ECD and more severe AD pathology in the brain, as well as worse cognitive functions than the control groups, which were immunized with Re-p75ECD (the reverse sequence of p75ECD) and phosphate-buffered saline, respectively. These findings demonstrate the impact of p75ECD-NAbs on p75NTR/p75ECD imbalance, providing a novel insight into the role of autoimmunity and p75NTR in AD.

Upregulation of microRNA-34a enhances myocardial ischemia-reperfusion injury via the mitochondrial apoptotic pathway.

Mitochondrial oxidative injury can result in many cardiovascular diseases including cardiac ischemia-reperfusion (I/R) injury. This study was designed to investigate whether microRNA-34a (miR-34a) influences cardiac I/R or hypoxia/reoxygenation (H/R) injury by regulating the mitochondrial apoptotic pathway from oxidative injury.In vivo, myocardial infarction size was examined by Evan blue/TTC staining. Apoptosis was assessed by TUNEL assay. Heart function was measured by echocardiography. Lactate dehydrogenase (LDH) and creatine kinase (CK) were evaluated. In vitro, H9c2 cardiomyocytes were exposed to H/R stimulation. Cell viability was assessed by the CCK-8 assay and apoptosis was detected by Annexin V/PI staining. Mitochondrial superoxide, mitochondrial membrane potential (MMP) and ATP production was evaluated by detection kits, and related proteins were detected by western blotting analysis. We observed that the level of miR-34a was significantly upregulated in I/R rats compared to the sham group. Injection of adenovirus inhibiting miR-34a into the left ventricular anterior wall improved heart function and decreased I/R injury. H9c2 cardiomyocytes exposed to H/R stimulation displayed an obvious increase in miR-34a expression. In addition, miR-34a inhibitor alleviated, whereas miR-34a mimic aggravated H/R-induced mitochondrial injury. Bcl-2 was identified as a target gene of miR-34a by dual-luciferase reporter gene detection. Knockdown of Bcl-2 abolished the cardioprotection of the miR-34a inhibitor in H9c2 cells. In summary,our study demonstrates that inhibition of miR-34a exhibits therapeutic potential in treatment of myocardial I/R injury by restraining mitochondrial apoptosis.

Regulation of Neurogenesis and Neuronal Differentiation by Natural Compounds.

Neuronal damage or degeneration is the main feature of neurological diseases. Regulation of neurogenesis and neuronal differentiation is important in developing therapies to promote neuronal regeneration or synaptic network reconstruction. Neurogenesis is a multistage process in which neurons are generated and integrated into existing neuronal circuits. Neuronal differentiation is extremely complex because it can occur in different cell types and can be caused by a variety of inducers. Recently, natural compounds that induce neurogenesis and neuronal differentiation have attracted extensive attention. In this paper, the potential neural induction effects of medicinal plant-derived natural compounds on neural stem/progenitor cells (NS/PCs), the cultured neuronal cells, and mesenchymal stem cells (MSCs) are reviewed. The natural compounds that are efficacious in inducing neurogenesis and neuronal differentiation include phenolic acids, polyphenols, flavonoids, glucosides, alkaloids, terpenoids, quinones, coumarins, and others. They exert neural induction effects by regulating signal factors and cellspecific genes involved in the process of neurogenesis and neuronal differentiation, including specific proteins (ß-tubulin III, MAP-2, tau, nestin, neurofilaments, GFAP, GAP-43, NSE), related genes and proteins (STAT3, Hes1, Mash1, NeuroD1, notch, cyclin D1, SIRT1, Reggie-1), transcription factors (CREB, Nkx-2.5, Ngn1), neurotrophins (BDNF, NGF, NT-3), and signaling pathways (JAK/STAT, Wnt/ß-catenin, MAPK, PI3K/Akt, GSK-3ß/ß-catenin, Ca2+/CaMKII/ATF1, Nrf2/HO-1, BMP).The natural compounds with neural induction effects are of great value for neuronal regenerative medicine and provide promising prevention and treatment strategies for neurological diseases.