Nobiletin suppresses high-glucose-induced inflammation and ECM accumulation in human mesangial cells through STAT3/NF-κB pathway.

Diabetic nephropathy (DN) is a complication of chronic diabetes and the main cause of end-stage renal disease all over the world. Inflammation and extracellular matrix (ECM) accumulation play important roles in the pathogenesis of DN. Evidence suggested that nobiletin acts anti-inflammatory role and plays a critical role in diabetes; however, its role in DN remains unclear. In the current study, we promulgated the nobiletin involved in high-glucose-induced glomerular mesangial cell inflammation and ECM accumulation. Nobiletin treatment significantly abrogated high-glucose-induced glomerular mesangial cell proliferation. Nobiletin treatment markedly suppressed inflammation cytokine secretion, including interleukin (IL)-1ß, IL-6, tumor necrosis factor α, and monocyte chemoattractant protein 1 in high-glucose-induced glomerular mesangial cell. Also, exposed nobiletin to high-glucose-induced glomerular mesangial cell considerably reduced ECM accumulation through inhibited ECM-associated protein type 4 collagen and fibronectin expression. Furthermore, nobiletin treatment abolished nuclear factor κB (NF-κB) pathway activation through signal transducer and activator of transcription 3 (STAT3) inhibition. Overexpression STAT3 reversed the effects of nobiletin on high-glucose-induced glomerular mesangial cell proliferation, inflammation, ECM accumulation, and NF-κB pathway activation. Hence, our results suggest that nobiletin play roles in high-glucose-induced glomerular mesangial cells through inhibiting inflammation and ECM accumulation, and the STAT3/NF-κB pathway was involved in the function of nobiletin.

Inhibitory effects of tubeimoside I on synoviocytes and collagen-induced arthritis in rats.

Advancements in rheumatoid arthritis (RA) therapies have shown considerable progresses in the comprehension of disease. However, the development of new potential medicines with relative safety and efficacy continues and natural compounds have been considered as alternatives or complementary agents to gain immense attractions. Tubeimoside I (TBMS I), a main triterpenoid saponin isolated from Bolbostemma paniculatum, has been reported to possess antiviral and anticancer effects. However, its effect on RA remains unknown. Here, we investigated the therapeutic effect of TBMS I in collagen-induced arthritis (CIA) rats and explored its underlying mechanism. Our results showed that TBMS I treatment efficaciously ameliorated inflammation and joint destruction of rats with CIA. In vitro studies revealed that TBMS I suppressed the production of pro-inflammatory cytokines including IL-1ß, IL-6, IL-8 and TNFα, and downregulated the expression of MMP-9. In addition, TBMS I attenuated the destructive phenotypes of FLS of CIA rats including inhibiting proliferation and reducing migration rate. Further mechanistic analysis demonstrated that TBMS I suppressed TNFα-induced activations of NF-κB and MAPKs (p38 and JNK) leading to the downregulation of pro-inflammatory cytokines, which was beneficial to the anti-proliferative and anti-migratory activities of FLS cells. Taken together, TBMS I has a great potential to be developed into a novel therapeutic agent for the treatment of RA.

Carnosic acid inhibits inflammation response and joint destruction on osteoclasts, fibroblast-like synoviocytes, and collagen-induced arthritis rats.

The discovery of new therapeutic drugs with the ability of preventing inflammation and joint destruction with less adverse effects is urgently needed for rheumatoid arthritis (RA). Carnosic acid (CA), a major phenolic compound isolated from the leaves of Rosemary (Rosmarinus officinalis L.), has been reported to have antioxidative and antimicrobial properties. However, its effects on RA have not been elucidated. Here, we investigated the effects of CA on osteoclasts and fibroblast-like synoviocytes in vitro and on collagen-induced arthritis (CIA) in Wistar rats in vivo. Our in vitro and in vivo studies showed that CA suppressed the expression of pro-inflammatory cytokines including TNFɑ, IL-1ß, IL-6, IL-8, IL-17 and MMP-3, and downregulated the production of RANKL. More importantly, we observed that CA inhibited osteoclastogenesis and bone resorption in vitro and exerted therapeutic protection against joint destruction in vivo. Further biochemical analysis demonstrated that CA suppressed RANKL-induced activations of NF-κB and MAPKs (JNK and p38) leading to the downregulation of NFATc1. Taken together, our findings provide the convincing evidence that rosemary derived CA is a promising natural compound for the treatment of RA.

Jatrorrhizine Hydrochloride Suppresses Proliferation, Migration, and Secretion of Synoviocytes In Vitro and Ameliorates Rat Models of Rheumatoid Arthritis In Vivo.

Jatrorrhizine hydrochloride (JH), an active component isolated from the traditional Chinese herb Coptis chinensis, has been reported to have antimicrobial, antitumor, antihypercholesterolemic, and neuroprotective activities. However, its antirheumatoid arthritis (RA) property remains unknown. In this study, a collagen-induced arthritis (CIA) rat model was used to evaluate the therapeutic effects of JH on RA by using arthritis score, radiological evaluation, and histopathological assessment. The in vitro effects of JH on proliferation, migration, and production of inflammatory mediators in RA-derived fibroblast-like synoviocyte MH7A cells were determined by the EdU incorporation assay, wound healing assay, real-time PCR, and ELISA, respectively. The in vivo studies showed that JH treatment significantly prevented the progression and development of RA in CIA rats through anti-inflammation and suppressing bone destruction. The in vitro studies revealed that JH could effectively attenuate the destructive phenotypes of MH7A cells, including inhibiting proliferation, migration, and production of inflammatory mediators. Further mechanistic analysis demonstrated that JH suppressed tumor necrosis factor alpha (TNFα)-stimulated activations of nuclear factor of kappaB (NF-κB) and mitogen-activated protein kinases (MAPKs) (ERK and p38) leading to the downregulation of proinflammatory cytokines, which might be beneficial to the antiproliferative and antimigratory activities of FLS cells. Collectively, our results demonstrated that JH has a great potential to be developed into a novel therapeutic agent for treating RA.

Laser doping of 2D material for precise energy band design.

The number of excellent 2D materials is finite for nano optoelectric devices including transistors, diodes, sensors, and so forth, thus the modulation of 2D materials is important to improve the performance of the current eligible 2D materials, and even to transform unqualified 2D materials into eligible 2D materials. Here we develop a fine laser doping strategy based on highly controllable laser direct writing, and investigate its effectivity and practicability by doping multilayer molybdenum ditelluride (MoTe2). Power-gradient laser doping and patterned laser doping, for the first time, are presented for designable and fine doping of 2D materials. The laser-induced polar transition of MoTe2 indicates good controllability of the method for the carrier concentration distribution in MoTe2. Multiple devices with finely tuned energy band structures are demonstrated by means of power-gradient laser doping and patterned laser doping, further illustrating the design capability of a precise energy band in 2D materials.

Muscone improves hypoxia/reoxygenation (H/R)-induced neuronal injury by blocking HMGB1/TLR4/NF-κB pathway via modulating microRNA-142.

Previous reports have indicated that natural muscone has neuroprotective effects against cerebral hypoxia injury; however, little is known in regards to its pharmacological mechanism. In this study, we tried to evaluate the neuroprotective effects and mechanisms of muscone against cerebral hypoxia injury using an in vitro model. The cerebral hypoxia injury cell model was produced by hypoxia/reoxygenation (H/R). The cell viability and apoptosis were measured using the cell counting Kit-8 and the Annexin V-FITC/PI Apoptosis Detection kit, respectively. To screen microRNAs regulated by muscone, we analyzed the gene expression datasets of GSE84216 retrieved from gene expression omnibus (GEO). Here, it was demonstrated that muscone treatment significantly alleviated the cell apoptosis, oxidative stress and inflammation in H/R-exposed neurons. Subsequently, through analyzing GSE84216 from the GEO database, miR-142-5p was markedly upregulated by treatment of muscone in this cell model of cerebral hypoxia injury. Further experiments revealed that downregulation of miR-142-5p eliminated the neuroprotective effects of muscone against H/R induced neuronal injury. Additionally, high mobility group box 1 (HMGB1), an important inflammatory factor, was identified as a direct target of miR-142-5p in neurons. Meanwhile, we further demonstrated that muscone could reduce the expression of HMGB1 by upregulating miR-142-5p expression, which subsequently resulted in the inactivation of TLR4/NF-κB pathway, finally leading to the improvement of cell injury in H/R-exposed neurons. Overall, we demonstrate for the first time that muscone treatment alleviates cerebral hypoxia injury in in vitro experiments through blocking activation of the TLR4/NF-κB signaling pathway by targeting HMGB1, suggesting that muscone may serve as a potential therapeutic drug for treating cerebral hypoxia injury.

A REPORT OF RADIATION RISKS DURING AND AFTER PROCESSING MINERAL PLACER FROM SOUTHEAST AFRICA.

Recently, high levels of radioactivity were found in products from Chinese mineral processing industries that handle mineral placer from Southeast Africa. The findings led to public panic. The aim of this work is to provide radiological data for the government, workers and the public. In this work, activity concentrations of 238U,232Th,226Ra and40 K in raw ore from Southeast Africa were analysed in the laboratory. Products like monazite and building material were analysed. High concentrations of 238U,232 Th and 226Ra in products were found to be at a level of 104  Bq/kg. Around the South China Mineral Processing Industry, radioactivity in soil and groundwater was analysed. Absorbed dose rates in air and indoor radon concentrations at workplaces were monitored. Annual effective dose to workers and the public was calculated and found to exceed Chinese dose criterion. This report might be an alert for mining and mineral processing in Southeast Africa.

circFADS2 regulates lung cancer cells proliferation and invasion via acting as a sponge of miR-498.

CircRNAs could play critical functions in tumor progression. However, the expression and underlying mechanism of circRNAs in lung cancer progression remain poorly defined. In the present study, high-throughput microarray assay revealed that hsa_circRNA_100833 (identified as circFADS2) was markedly evaluated in lung cancer tissues, and it was further validated by qRT-PCR. High expression of circFADS2 was correlated with advanced TNM stage, lymph node metastasis, poor differentiation, and shorter overall survival of NSCLC patients. In vitro assays results showed that circFADS2 inhibition suppressed lung cancer cells proliferation and invasion ability. Bioinformatics analysis showed that miR-498 contained the complementary binding region of circFADS2, which was confirmed by Dual-luciferase reporter assay. In addition, the expression of miR-498 was down-regulated and negatively associated with circFADS2 expression in nonsmall cell lung cancer. Furthermore, rescue assays showed that miR-498 inhibitors abolished the effects of circFADS2 inhibition on lung cancer cells progression. Taken together, our findings indicated that circFADS2 was an effective tumor promoter in lung cancer progression, and its functions were performed by regulating the expression of miR-498. These data suggested that circFADS2 could act as a target for lung cancer treatment.

The 4.438 MeV gamma to neutron ratio for the Am-Be neutron source.

An accurate measurement of the 4.438 MeV gamma-ray to total neutron ratio, namely R=Sgamma/Sn, for a Chinese-made Am-Be neutron source is described. The neutron strength of the source relative to a previously standardized source was determined by the manganese bath technique. The gamma-rays spectra of the source were measured using a Ø 75 x 75 mm NaI(Tl) detector. The background induced by neutrons and the absolute full energy peak efficiency of the detector were calculated using the MCNP code. The experimental ratio so obtained agrees well with the calculated value. A synthetic evaluated and recommended value of R=0.575+/-4.8% was given. We conclude that the experimental R-value appears an important characteristic for an Am-Be source.

Measurement of neutron capture cross sections for 141Pr from 0.5 to 1.6 MeV.

Cross sections of 141Pr(n,gamma) 142Pr reaction are measured at neutron energies of 0.54, 1.09 and 1.59 MeV using the activation method. The activities of the products are counted with a high resolution HPGe detector gamma-ray spectrometer. The neutron fluence is determined by 197Au(n,gamma)198 Au reaction cross sections. The errors of the measured results are +/-6-7%. The neutron capture cross sections for this reaction are also calculated with the NUNF code. Our results are compared with those of other authors. Recommendations for inclusion of data in the energy region 0.05-3.90 MeV are made, these being in good agreement with the ENDF/B-VI data.

New calculations of neutron kerma coefficients and dose equivalent.

For neutron energies ranging from 1 keV to 20 MeV, the kerma coefficients for elements H, C, N, O, light water, and ICRU tissue were deduced respectively from microscopic cross sections and Monte Carlo simulation (MCNP code). The results are consistent within admitted uncertainties with values evaluated by an international group (Chadwick et al 1999 Med. Phys. 26 974-91). The ambient dose equivalent generated in the ISO-recommended neutron field for an Am-Be neutron source (ISO 8529-1: 2001(E)) was obtained from the kerma coefficients and Monte Carlo calculation. In addition, it was calculated directly by multiplying the neutron fluence by the fluence-to-ambient dose conversion coefficients recommended by ICRP (ICRP 1996 ICRP Publication 74 (Oxford: Pergamon)). The two results agree well with each other. The main feature of this work is our Monte Carlo simulation design and the treatments differing from the work of others in the calculation of neutron energy transfer in non-elastic processes.