Search

Persistent microglia-mediated neuroinflammation contributes to the progressive loss of dopaminergic (DA) neurons in Parkinson's disease (PD). Recently, NOD-like receptor protein 3 (NLRP3) inflammasome-mediated neuroinflammation is considered to influence the pathogenesis of PD profoundly. Promoting DA neuron survival and/or inhibiting neuroinflammation may offer neuroprotection for PD. In the present study, we found that echinacoside (ECH), a phenylethanoid glycoside derived from Cistanche Deserticola, ameliorated motor deficit induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in a mouse PD model, characterized as decreased mobility distance in open field test and average time in rotarod test, as well as increased turn time and total time in pole test. ECH administration promoted the reduction of tyrosine hydroxylase (TH) expression and the number of TH-positive neurons in the substantia nigra (SN) under MPTP injury as the molecular docking simulation predicted that ECH would interact with TH. Moreover, ECH improved cell viability in MPP+-damaged SH-SY5Y cell, a cell line for DA neuron, in vitro. Furthermore, ECH administration alleviated MPTP-triggered microglial activation, thus downregulated the expression and activation of NLRP3 inflammasomes in mice SN, along with the involved proteins including Caspase (CASP)-1 and interleukin-1β (IL-1β). The inhibition of NLRP3/CASP-1/IL-1β neuroinflammatory signaling was further confirmed in murine N9 microglia activated by MPP+ insult after ECH treatment in vitro. Furthermore, MCC950, a selective inhibitor for NLRP3 activation, reduced the enhancive expression of NLRP3/CASP-1/IL-1β in MPP+-insulted N9, and also facilitated the inhibition of inflammation synergistically mediated by ECH treatment. All the collected data revealed that ECH ameliorated PD mice neuroethology through promoting DA neuron survival and inhibiting the activated microglia-mediated NLRP3/CASP-1/IL-1β inflammatory signaling. These findings highlight the crucial roles of NLRP3 inflammasome involved in PD neuropathology and ECH exertes neuroprotection for PD as double-targeting neuroinflammation and DA neuronal survival.

Immune thrombocytopenia (ITP) is a heterogeneous autoimmune disorder characterized by immune-mediated platelet destruction, leading to lower platelet count. Thalidomide is considered as a novel immunomodulatory drug for treating several autoimmune diseases. Whether thalidomide can ameliorate ITP remains unclear. This study aims to evaluate the effect of thalidomide on ITP mouse model. ITP mouse model was established through intraperitoneal injection of rat anti-mouse integrin GPIIb/CD41 immunoglobulin. Thalidomide (10, 20 or 50 mg/kg body weight) was intraperitoneally injected into mice followed by antibody injection. Then, peripheral blood and plasma was isolated for analysis of platelet count and the level of IFN-γ and IL-17 in plasma. Meanwhile, spleen was extracted to measure the expression of CD68, a macrophage marker. In addition, macrophage cell line RAW264.7 was cultured and treated with thalidomide followed by analysis of cell viability, apoptosis as well as cell cycle. Thalidomide prevented antiplatelet antibody-mediated platelet destruction in ITP mouse model. Compared with vehicle (phosphate-buffered saline), thalidomide significantly inhibited the secretion of IFN-γ and IL-17 in ITP mouse and reduced the expression of CD68 in spleen. After thalidomide treatment, the cell viability of RAW264.7 cell was significantly reduced and the cell number in S phase was also significantly decreased. In addition, the expression of cyclin E2 was significantly reduced. In conclusion, thalidomide prevents antiplatelet antibody-mediated platelet destruction in ITP mouse possibly through reducing the number of macrophages, suggesting that it might be a novel approach for treating ITP.

A density functional study of the [2 + 2] cycloaddition between methyleneindolinones and enals catalyzed by prolinol derivatives is presented here. The calculations show that dienamines could be generated under acid-free conditions, and the hydroxyl of the catalysts plays a key role in the formation of dienamines. The following cycloaddition process between methyleneindolinones and the new formed dienamines includes two-step intramolecular electron transfers. The stereoselectivity is mainly attributed to the charge distributions on the reaction centers and the H-bonding interaction between the catalysts and methyleneindolinones. The excellent 3,4-regioselectivity is largely ascribed to the fact that the pre-product of 1,2-reactivity is tough to hydrolyze, but could return to the precursor. Besides, the large steric hindrance of catalysts is not conducive to the 3,4-reactivity, while the H-bonding between the catalysts and methyleneindolinones has less effect on the regioselectivity.

Five novel di- and tetra-nuclear rare earth complexes were synthesized by the variation of the solvent molecules: [Nd2(dbm)2(L)2(CH3OH)2]·0.75CH3OH (1), [Dy2(dbm)2(L)2(CH3OH)2]·4CH3OH (2), [Dy4(dbm)8(L)2(C3H7OH)2]·C3H7OH·2CH3CN (3), [Yb4(dbm)8(L)2(C3H7OH)2]·8CH3CN (4), [Y4(dbm)6(L)2(μ3-OH)2]·2CH3CN (5) (H2L = 2-[(2-hydroxyimino)propanehydrazide)methyl]-8-hydroxyquinoline, Hdbm = dibenzoylmethane). The structures of the complexes gradually transition from tetra-nuclear square grid-like clusters (5) to di-nuclear structure (1 and 2), and finally to tetra-nuclear chain clusters (3 and 4) with the increase of the alkyl chain of solvent molecules (μ3-OH → CH3OH → C3H7OH). 1 and 4 in the solid-state display the typical emissions of the NdIII ions and YbIII ions in the near-infrared region under visible-light excitation. For 2, more than one distinct relaxation process can be observed with an effective energy barrier ΔE/kB = 21.45 K, which is a typical behavior of single-molecule magnets (Hdc = 1000 Oe). This research shows that the magnetic properties can be modulated by tuning the solvent molecules to regulate the structures of complexes.

Liposomes are the most widely used nanocarrier platform for the delivery of therapeutic and diagnostic agents, and a number of liposomes have been approved for use in clinical practice. After systemic administration, most liposomes are cleared by macrophages in the mononuclear phagocyte system, such as the liver and bone marrow (BM). However, the majority of studies have focused on investigating the therapeutic results of liposomal drugs, and too few studies have evaluated the potential side effects of empty nanocarriers on the functions of macrophages in the mononuclear phagocyte system. Here, we evaluate the potential effects of empty liposomes on the functions of BM niche macrophages. Following liposome administration, we observed lipid droplet (LD) accumulation in cultured primary macrophages and BM niche macrophages. We found that these LD-accumulating macrophages, similar to foam cells, exhibited increased expression of inflammatory cytokines, such as IL-1β and IL-6. We further provided evidence that liposome deposition and degradation induced LD biogenesis on the endoplasmic reticulum membrane and subsequently disturbed endoplasmic reticulum homeostasis and activated the inositol-requiring transmembrane kinase/endoribonuclease 1α/NF-κB signaling pathway, which is responsible for the inflammatory activation of macrophages after liposome engulfment. Finally, we also showed the side effects of dysfunctional BM niche macrophages on hematopoiesis in mice, such as the promotion of myeloid-biased output and impairment of erythropoiesis. This study not only draws attention to the safety of liposomal drugs in clinical practice but also provides new directions for the design of lipid-based drug carriers in preclinical studies.

One of the most appealing strategies to address the problems of global warming and energy shortage is to develop clean and sustainable energy source. To this end, considerable efforts have been devoted to designing well-defined catalysts for energy conversion. As an earth-abundant transition metal, nickel has been regarded to be an important catalytic center in molecular catalysts for redox reactions related to energy conversion. This Review focuses on the properties of nickel complexes as molecular catalysts in energy conversion driven by electricity or light, including water splitting and carbon dioxide (CO2) reduction.

As the key component of glutathione peroxidase with unique antioxidant properties, selenium has been considered to play an important part on lipid metabolism. However, the associations of serum selenium concentrations with lipid concentrations and dyslipidemia are still controversial.We analyzed cross-sectional data including serum selenium levels, lipid concentrations and other related indexes of 8198 rural Chinese. Serum selenium was measured by inductively coupled plasma mass spectrometry, and total cholesterol (TC), triglyceride (TG), high density lipoprotein-cholesterol (HDL-c) and low density lipoprotein-cholesterol (LDL-c) of serum were measured with kits.Overall, mean serum selenium was 120 μg/l. Multivariate liner regression revealed that selenium concentrations were positively correlated with TC (P 0.001), HDL-c (P 0.001), TG (P 0.001) and LDL-c (P 0.001). Compared with the lowest quintile of serum selenium, participants in quintile 3, 4 and 5 had higher risks of High-TC dyslipidemia (P ≤ 0.02) and High-LDLC dyslipidemia (P 0.02) after adjusting for covariates. In the stratified analyses, we found that the selenium-dyslipidemia associations were significantly stronger in post-menopausal women (OR: 2.72; 95% CI: 1.97, 4.17) and diabetics (OR: 9.40; 95% CI: 3.02, 29.26).Elevated serum selenium levels were correlated with the increased concentrations of TC, LDL-c, HDL-c and TG, and increased the risk of High-TC and High-LDLC dyslipidemia among rural Chinese. However, the real associations between serum selenium and lipid profile should be verified in specifically designed randomized trials in future.

To accelerate the mulberry breeding program and examine the genome size and ploidy levels of 27 mulberry accessions of promising lines in Taiwan, nuclei suspensions were prepared from unfolded young leaves and analyzed by a flow cytometer. The genome size of each accession was estimated by referring to the standard genome size of chicken erythrocyte nuclei (CEN, 2.5 pg). Our results indicated that 25 among 27 investigated accessions in M. bombycis, M. alba, M. latifolia, M. australis, M. formosnensis, and M. atropurpurea are diploids with genome sizes ranging from 0.61 to 0.71 pg. ‘Elongated mulberry No. 1’ (M. laevigata) with a genome size of 1.06 pg is a triploid. Two populations were identified in the accession ‘67C001’ (M. australis Poir.) with a genome size of either 0.63 pg or 0.98 pg. Due to their similarity in appearance, we suspected that they are probably from the same origin, thus warranting further investigations. Several important vegetative characters of diploids and triploids have been estimated, including leaf length, leaf width, petiole length, petiole width, leaf thickness, and internode length, to document their correlation using the unpaired t-test. Subsequently, the statistical relationship between diploid and triploid species on some of these important characters, including leaf width, petiole width and internode length, was determined through binary regression analysis. We suggested that the internode length could provide a beneficial index to distinguish individuals with different ploidy levels in the field. Results of this study provide useful information to clarify the taxonomy of Morus and improve breeding programs aiming to advance horticulture and sericulture.

The intramolecular [2+2] cycloaddition of 1,3-dienes under visible light irradiation investigated by Yoon and his co-workers shows remarkably high yield and stereoselective differences under different photocatalysts. The reaction was speculated to be induced by energy transfer. However, the origin for these phenomena is still unclear. In this scene, the detailed mechanism for the [2+2] cycloaddition of 1,3-dienes under visible light has been investigated using density functional theory B3LYP and TPSSTPSS methods. The result shows that the reaction not only can be induced by energy transfer between photocatalysts and reactants, but also can be induced by electron transfer between them. The [2+2] cycloaddition induced by energy transfer is carried out along the potential energy surface (PES) of triplet excited states (T1) firstly, and then goes back to the singlet ground state (S0) via MECPs (minimum energy crossing points) between the PESs of the S0 and T1 states, forming the product in the S0 state. The [2+2] reaction induced by electron transfer proceeds along the doublet state PES of the cation radical reactant and the neutral four-membered ring product could be obtained by electron transfer from the corresponding reactant or reduced photocatalyst. The origin of stereoselectivity of the [2+2] reaction is attributed to the reaction mechanism difference under different photocatalysts.

Immune thrombocytopenia (ITP) is an autoimmune disease, which is characterized by abnormal of T immunity. A disintegrin and metalloproteinase (ADAM) 10, a member of proteinase family, has been demonstrated to regulate T cell proliferation and effector function. Considering the closely association of dysregulation of T cell function with ITP, whether ADAM10 involves in the pathogenesis of ITP remains unclear. In this study, 54 active ITP patients, 18 ITP in remission and 24 age and gender matched healthy control were enrolled. Peripheral blood mononuclear cells (PBMCs) were isolated from patients and control for isolation of RNA and plasma which were used to measure mRNA level of ADAM10 and tissue inhibitor of metalloproteinase 3 (TIMP3) by quantitative real-time PCR and soluble level of FasL and lymphocyte activation gene-3 (LAG-3) in plasma by ELISA. Meanwhile, T cell activation was measured by flow cytometry. Our results showed significantly higher expression of ADAM10 and lower expression of TIMP3 in active ITP patients compared with control, which were all restored into normal level in remission patients. Consistent with the expression profile of ADAM10, increased soluble plasma level of FasL and LAG-3 were observed in active ITP patients and reduced to normal level in patients in remission. Furthermore, increased T cell activation as demonstrated by higher expression of HLA-DR and CD69 were found in active ITP patients. In conclusion, elevated expression of ADAM10 was associated with the pathogenesis and development of ITP and therapeutically targeting it might be a novel approach for the treatment of ITP.