Dysregulation of intercellular signaling by MOF deletion leads to liver injury.

Epigenetic mechanisms that alter heritable gene expression and chromatin structure play an essential role in many biological processes, including liver function. Human MOF (males absent on the first) is a histone acetyltransferase that is globally downregulated in human steatohepatitis. However, the function of MOF in the liver remains unclear. Here, we report that MOF plays an essential role in adult liver. Genetic deletion of Mof by Mx1-Cre in the liver leads to acute liver injury, with increase of lipid deposition and fibrosis akin to human steatohepatitis. Surprisingly, hepatocyte-specific Mof deletion had no overt liver abnormality. Using the in vitro coculturing experiment, we show that Mof deletion-induced liver injury requires coordinated changes and reciprocal signaling between hepatocytes and Kupffer cells, which enables feedforward regulation to augment inflammation and apoptotic responses. At the molecular level, Mof deletion induced characteristic changes in metabolic gene programs, which bore noticeable similarity to the molecular signature of human steatohepatitis. Simultaneous deletion of Mof in both hepatocytes and macrophages results in enhanced expression of inflammatory genes and NO signaling in vitro. These changes, in turn, lead to apoptosis of hepatocytes and lipotoxicity. Our work highlights the importance of histone acetyltransferase MOF in maintaining metabolic liver homeostasis and sheds light on the epigenetic dysregulation in liver pathogenesis.

LncRNA SNHG14 contributes to proinflammatory cytokine production in rheumatoid arthritis via the regulation of the miR-17-5p/MINK1-JNK pathway.

Rheumatoid arthritis (RA) is a widespread autoimmune disorder of the joints. Long noncoding RNAs (lncRNAs) have been reported to participate in the pathogenesis of RA by serving as competitive endogenous RNAs. LncRNA small nucleolar RNA host gene 14 (SNHG14) is involved in the development of various diseases. Here, we found that high expression of SNHG14 in RA was closely related to the disease activity. Functional assays indicated that SNHG14 knockdown obviously hampered phorbol myristate acetate-activated THP-1 (pTHP-1) cell proliferation and proinflammatory cytokines production. In mechanism, SNHG14 served as a sponge of microRNA-17-5p (miR-17-5p), and misshapen like kinase 1 (MINK1) was a target of miR-17-5p. SNHG14 depletion-induced inhibitory effects on cell proliferation and inflammatory response were reversed by MINK1 overexpression in macrophages. Moreover, SNHG14 promoted the jun N-terminal kinase (JNK) signaling via the miR-17-5p/MINK1 axis. Overall, SNHG14 boosted the process of RA by MINK1 activating the JNK pathway.

Somatic mutations in colorectal cancer are associated with the epigenetic modifications.

Colorectal cancer (CRC) mostly arises from progressive accumulation of somatic mutations within cells. Most commonly mutated genes like TP53, APC and KRAS can promote survival and proliferation of cancer cells. Although the molecular alterations and landscape of some specific mutations in CRC are well known, the presence of a somatic mutation signature related to genomic regions and epigenetic markers remain unclear. To find the signatures from a random distribution of somatic mutations in CRCs, we carried out enrichment analysis in different genomic regions and identified peaks of epigenetic markers. We validated that the mutation frequency in miRNA is dramatically higher than in flanking genomic regions. Moreover, we observed that somatic mutations in CRC and colon cancer cell lines are significantly enriched in CTCF binding sites. We also found these mutations are enriched for H3K27me3 in both normal sigmoid colon and colon cancer cell lines. Taken together, our findings suggest that there are some common somatic mutations signatures which provide new directions to study CRC.

Anti-N-Methyl-D-Aspartic Acid Receptor 2 (Anti-NR2) Antibody in Neuropsychiatric Lupus Serum Damages the Blood-Brain Barrier and Enters the Brain.

BACKGROUND Brain microvessel endothelial cells constitute an important component in the blood-brain barrier. Cell-culture-based models of the blood-brain barrier (BBB) have been extensively applied in pharmacology, pathology and physiology. This study investigated effects of anti-N-methyl-D-aspartic acid receptor 2 (anti-NR2), N-methyl-D-aspartic acid (NMDA) receptor antibodies, NMDA receptor antagonists, and NMDA receptor agonists on brain microvessel endothelial cell models, and verified the effect of anti-NR2 antibody on the BBB as a receptor agonist. MATERIAL AND METHODS The primary brain microvessel endothelial cells were isolated and cultured, and an in vitro BBB model was established based on microvessel endothelial cells. Anti-NR2 antibody, glutamic acid, ifenprodil, and memantine were added in the BBB model to analyze changes in transepithelial electrical resistance (TEER) and to examine the permeability of the brain microvessel endothelial cell model. RESULTS The results showed that TEER values were significantly decreased by the addition of anti-NR2 antibody and glutamate, but were significantly increased by the addition of ifenprodil and memantine. TEER values showed no changes when treated by anti-NR2 antibody and ifenprodil, as well as anti-NR2 antibody and memantine. When dexamethasone was added, the TEER values increased by 23.8%, 39.4%, and 29.6% by treating with anti-NR2 antibody, positive cerebrospinal fluid, and positive serum, respectively. CONCLUSIONS Our findings show that anti-NR2 antibody in neuropsychiatric lupus serum can damage the BBB and enter the brain.

Rapamycin Combi with TAE on the Growth, Metastasis, and Prognosis of Hepatocellular Carcinoma in Rat Models.

INTRODUCTION AND AIM: To investigate the effect of mTOR inhibitor Rapamycin combined with transcatheter arterial embolization (TAE) on the growth, metastasis, and prognosis of hepatocellular carcinoma (HCC) in rat model. MATERIAL AND METHOD: McARH7777 cells were used to construct rat models of HCC, which were randomly divided into Model, Rapamycin, TAE, and Rapamycin + TAE groups. Quantitative reverse transcription-PCR (qRT-PCR) and Western Blot were used to detect the expression of Epithelial-Mesenchymal Transition (EMT)-related molecules, and immunohistochemical staining to determine the expression of EMTrelated proteins, angiogenic factors as well as microvessel density (MVD)-CD34. RESULTS: The hepatic tumor volume of rats in the other three groups were all significantly smaller than the Model group on the 7th, 14th, and 21st day after treatment and the combination treatment was apparently more effective than either treatment alone. Besides, both the number and the size of metastatic nodules of HCC rats after combination treatment were remarkably reduced. In addition, compared with rats in the Rapamycin + TAE group, N-cadherin, Vimentin, HIF-1α, VEGF, and MVD-CD34 were obviously enhanced, while E-cadherin was lowered in those TAE group, which were the complete opposite to the Rapamycin group. Besides, the median survival time of rats in the Rapamycin + TAE group was evidently longer than the resting groups. CONCLUSION: Rapamycin combined with TAE may effectively suppress the EMT formation and angiogenesis, thereby inhibiting the growth and lung metastasis of HCC rats, which provides a new idea for countering the recurrence and metastasis of HCC.

Reducing Hysteresis and Enhancing Performance of Perovskite Solar Cells Using Low-Temperature Processed Y-Doped SnO2 Nanosheets as Electron Selective Layers.

Despite the rapid increase of efficiency, perovskite solar cells (PSCs) still face some challenges, one of which is the current-voltage hysteresis. Herein, it is reported that yttrium-doped tin dioxide (Y-SnO2 ) electron selective layer (ESL) synthesized by an in situ hydrothermal growth process at 95 °C can significantly reduce the hysteresis and improve the performance of PSCs. Comparison studies reveal two main effects of Y doping of SnO2 ESLs: (1) it promotes the formation of well-aligned and more homogeneous distribution of SnO2 nanosheet arrays (NSAs), which allows better perovskite infiltration, better contacts of perovskite with SnO2 nanosheets, and improves electron transfer from perovskite to ESL; (2) it enlarges the band gap and upshifts the band energy levels, resulting in better energy level alignment with perovskite and reduced charge recombination at NSA/perovskite interfaces. As a result, PSCs using Y-SnO2 NSA ESLs exhibit much less hysteresis and better performance compared with the cells using pristine SnO2 NSA ESLs. The champion cell using Y-SnO2 NSA ESL achieves a photovoltaic conversion efficiency of 17.29% (16.97%) when measured under reverse (forward) voltage scanning and a steady-state efficiency of 16.25%. The results suggest that low-temperature hydrothermal-synthesized Y-SnO2 NSA is a promising ESL for fabricating efficient and hysteresis-less PSC.

LncRNA TUG1 influences papillary thyroid cancer cell proliferation, migration and EMT formation through targeting miR-145.

LncRNA TUG1, a tumor oncogene associated with various human cancers, has been reported to be involved in regulating various cellular processes, such as proliferation, apoptosis and invasion through targeting multiple genes. However, its biological function in thyroid cancer cells has not been elucidated. The aim of this study is to measure TUG1 expression level and evaluate its function in thyroid cancer cells. LncRNA TUG1 expression levels in thyroid cancer tissues and three thyroid cancer cell lines (the ATC cell lines SW1736 and KAT18 and the FTC cell line FTC133) were assessed by qRT-PCR and compared with that of the human normal breast epithelial cell HGC-27. MTT assay, colony formation assay, transwell assay and western blot analysis were performed to assess the effects of TUG1 on proliferation, metastasis and EMT formation in thyroid cancer cells in vitro. Rescue assay was performed to further confirm that TUG1 contributes to the progression of thyroid cancer cells through regulating miR-145/ZEB1 signal pathway. LncRNA TUG1 was found to be up-regulated in thyroid cancer tissues and thyroid cancer cells compared with that in the human normal breast epithelial cell HGC-27. Increased lncRNA TUG1 expression was found to significantly promote tumor cell proliferation, and facilitate cell invasion, while down-regulated TUG1 could obviously inhibit cell proliferation, migration/invasion and reverse EMT to MET. These results indicated that TUG1 may contribute to the progression of thyroid cancer cells by function as a ceRNA competitive sponging miR-145, and that lncRNA TUG1 is associated with tumor progression in thyroid cancer cells.

Efficient planar Sb2S3 solar cells using a low-temperature solution-processed tin oxide electron conductor.

Efficient planar antimony sulfide (Sb2S3) heterojunction solar cells have been made using chemical bath deposited (CBD) Sb2S3 as the absorber, low-temperature solution-processed tin oxide (SnO2) as the electron conductor and poly (3-hexylthiophene) (P3HT) as the hole conductor. A solar conversion efficiency of 2.8% was obtained at 1 sun illumination using a planar device consisting of F-doped SnO2 substrate/SnO2/CBD-Sb2S3/P3HT/Au, whereas the solar cells based on a titanium dioxide (TiO2) electron conductor exhibited a power conversion efficiency of 1.9%. Compared with conventional Sb2S3 sensitized solar cells, the high-temperature processed mesoscopic TiO2 scaffold is no longer needed. More importantly, a low-temperature solution-processed SnO2 layer was introduced for electron transportation to substitute the high-temperature sintered dense blocking TiO2 layer. Our planar solar cells not only have simple geometry with fewer steps to fabricate but also show enhanced performance. The higher efficiency of planar Sb2S3 solar cell devices based on a SnO2 electron conductor is attributed to their high transparency, uniform surface, efficient electron transport properties of SnO2, suitable energy band alignment, and reduced recombination at the interface of SnO2/Sb2S3.

Low-temperature solution-processed tin oxide as an alternative electron transporting layer for efficient perovskite solar cells.

Lead halide perovskite solar cells with the high efficiencies typically use high-temperature processed TiO2 as the electron transporting layers (ETLs). Here, we demonstrate that low-temperature solution-processed nanocrystalline SnO2 can be an excellent alternative ETL material for efficient perovskite solar cells. Our best-performing planar cell using such a SnO2 ETL has achieved an average efficiency of 16.02%, obtained from efficiencies measured from both reverse and forward voltage scans. The outstanding performance of SnO2 ETLs is attributed to the excellent properties of nanocrystalline SnO2 films, such as good antireflection, suitable band edge positions, and high electron mobility. The simple low-temperature process is compatible with the roll-to-roll manufacturing of low-cost perovskite solar cells on flexible substrates.

Enhanced field emission from in situ synthesized 2D copper sulfide nanoflakes at low temperature by using a novel controllable solvothermal preferred edge growth route.

A facile one-pot solvothermal route using the reaction of sputtered copper film and sulfur powder in ethanol solution at a low temperature of 90 °C for 12 hours has been implemented to in situ synthesize 2D hexagonal copper sulfide (CuS) nanoflakes. Their field electron emission (FE) characteristics were investigated and were found to have a close relationship with the copper film's thickness. The lowest turn on electric field (Eon) was 2.05 V µm(-1) and the largest field enhancement factor (ß) was 7261 when the copper film's thickness was 160 nm. Furthermore, through a preferred edge growth route, patterned CuS nanoflakes were synthesized with the combined effect from a copper film seed layer and a passivation layer to further improve FE properties with an Eon of 1.65 V µm(-1) and a ß of 8351. The mechanism of the patterned CuS nanoflake preferred edge growth is reported and discussed for the first time.

Significance of m6A in subtype identification, immunological evolution, and therapeutic sensitivity of RA.

N6-methyladenosine (m6A) is one kind of important epigenetic modification pattern which is extensively involved in immune regulation. The development and progression of autoimmune diseases are closely related to immune dysregulation. Considering that rheumatoid arthritis (RA) is a typical autoimmune disease, the m6A process might be one of the important regulatory mechanisms in the pathogenesis of RA. In this study, we identified five differentially expressed m6A regulators in normal and RA samples from the GEO database. With these five regulators, we constructed the nomogram, and it could accurately identify the risk of RA morbidity. Next, we identified 121 differentially expressed genes (DEGs) between normal and RA samples, of which 36 DEGs were co-expressed with these five m6A regulators. We noted that these DEGs were highly enriched in multiple immunoregulatory signaling pathways, such as cytokine-mediated immune cell chemotaxis, adhesion, and activation. To further characterize the heterogeneity of immunological features, we clustered the RA samples into two subtypes. The C2 subtype has higher infiltration levels of pro-inflammatory cells and activity of pro-inflammatory signaling pathways. Thus, the inflammatory response might be more vigorous in the C2 subtype. Next, we constructed the m6Asig system with the SVM machine learning algorithms and least absolute shrinkage and selection operator (LASSO) regression. The m6Asig could accurately distinguish the C1 and C2 subtypes, which indicated that the m6Asig could be a potential biomarker for the inflammatory activity of RA. Finally, by comparing the information from the CellMiner, TTD, and DrugBank databases, we determined 25 drugs. The targets of these drugs were positively correlated with m6Asig. To be clarified, the above findings were derived from bioinformatics and statistical analyses, and further experimental validation still requires. In summary, this study further revealed the m6A and immunoregulation mechanisms in RA pathogenesis. Also, the m6Asig could be a novel biomarker with potential applicability in the clinical management of RA.

Irisin mitigates rheumatoid arthritis by suppressing mitochondrial fission via inhibiting YAP-Drp1 signaling pathway.

BACKGROUND: Irisin is a hormone-like factor secreted by muscle cells and produced by cleavage of the membrane protein fibronectin type III domain protein 5 (FNDC5), which exerts anti-inflammatory and anti-proliferative effects. However, the effects and the underlying mechanisms of irisin in rheumatoid arthritis (RA) are still unclear. METHOD: Collagen-induced arthritis (CIA) model was induced in DBA/1 mice and then treated with irisin. Arthritis index, paw thickness, weight, number of affected paws, serum inflammatory factors and related pathological tests were measured. RA fibroblast-like synoviocytes (RA-FLSs) were pretreated with IL-1ß and irisin, and the migration, proliferation, invasion, oxidative stress and mitochondrial related function of RA-FLSs were detected. RESULTS: Irisin significantly improved arthritis symptoms in CIA mice, as indicated by reduced arthritis index, alleviated paw thickness, decreased the number of affected paws and inhibited release of inflammatory factors. Irisin alleviated joint destruction, FLSs proliferation and the expression of YES-associated protein (YAP) and mitochondrial dynamic related protein 1 (Drp1) in the FLSs of CIA mice. In vitro experiment, irisin inhibited the proliferation, migration and invasion of RA-FLSs and improved oxidative stress induced by IL-1ß, thereby restraining the pathogenic transformation of RA-FLSs. Mechanically, irisin suppressed the nuclear translocation of YAP, in turn, could reduce the synthesis of Drp1 protein and inhibit the mitochondrial fission of RA-FLSs, which was reversed by YAP agonists. Therefore, irisin has a protective effect on RA. CONCLUSION: Irisin inhibits the proliferation, migration, invasion and inflammatory response of RA-FLSs by inhibiting the YAP-Drp1 signaling pathway, which implies a potential therapeutic effect on RA.

Photoacoustic Spectroscopy Gas Detection Technology Research Progress.

Photoacoustic spectroscopy (PAS) can be utilized as an ultrasensitive gas detection method. The basic principles of gas detection using PAS are discussed in this paper. First, the basic instrumentation for a PAS gas detection system is introduced focusing on the photoacoustic cell. The discussion includes non-resonant photoacoustic cells and the different types of resonant photoacoustic cells, including the longitudinal photoacoustic cell, the Helmholtz photoacoustic cell, the T-type photoacoustic cell, and the high-frequency resonant photoacoustic cell. The basic working principles of each of these, cells as well as the advantages and disadvantages of photoacoustic cells are discussed, and the development of newer types of photoacoustic cells in recent years is outlined in detail. This review provides detailed reference information and guidance for interested researchers who would like to design and build advanced photoacoustic cells for gas detection.

Lead-Free Halide Double Perovskite for High-Performance Photodetectors: Progress and Perspective.

Lead halide perovskite has become a promising candidate for high-performance photodetectors (PDs) due to its attractive optical and electrical properties, such as high optical absorption coefficient, high carrier mobility, and long carrier diffusion length. However, the presence of highly toxic lead in these devices has limited their practical applications and even hindered their progress toward commercialization. Therefore, the scientific community has been committed to searching for low-toxic and stable perovskite-type alternative materials. Lead-free double perovskite, which is still in the preliminary stage of exploration, has achieved inspiring results in recent years. In this review, we mainly focus on two types of lead-free double perovskite based on different Pb substitution strategies, including A2M(I)M(III)X6 and A2M(IV)X6. We review the research progress and prospects of lead-free double perovskite photodetectors in the past three years. More importantly, from the perspective of optimizing the inherent defects in materials and improving device performance, we propose some feasible pathways and make an encouraging perspective for the future development of lead-free double perovskite photodetectors.

Precise diagnosis and successful surgical intervention of the median arcuate ligament syndrome: A case report.

INTRODUCTION AND IMPORTANCE: The median arcuate ligament syndrome (MALS) is a rare disorder that produces a spectrum of symptoms due to compression of the arcuate ligament, clinically manifested primarily by abdominal pain, nausea, vomiting, and weight loss. The mechanism of these symptoms has not yet been revealed, and the current treatment methods are still somewhat controversial. CASE PRESENTATION: We present a 54-year-old woman who presented with intermittent epigastric pain for nine months. During the onset, she lost 7.5 kg. After routine examinations in a nearby hospital, no abnormality was found. She was referred to us. CTA showed compression of the celiac artery. Further selective celiac angiography at the end of inspiration and expiration confirmed MALS. After consultation with the patient, the decision to have a laparotomy was made. The celiac artery was completely skeletonized, and external compression on the artery was released. Postoperative symptoms improved significantly. One-year follow-up after the operation, she had a weight gain of 4.8 kg and was satisfied with the surgical results. CLINICAL DISCUSSION: The manifestations of MALS are varied and challenging. Our patient presented with weight loss and intermittent abdominal pain. The mutual confirmation of multiple investigations can provide a more comprehensive overview of celiac artery compression. We confirmed using ultrasonography, CT angiography, and selective digital subtraction angiography in this case. The celiac artery compression was relieved after open surgery. Our patient's symptoms improved significantly after surgery. We hope our treatment method can provide a reference for MALS diagnosis and treatment. CONCLUSION: It is challenging to diagnose MALS. Cross-confirmation of multiple examinations can provide a more comprehensive view of celiac compression. Surgical decompression of the celiac artery (open or laparoscopic surgery) may be an effective therapy for MALS, especially in centers with experience.

Noninvasive Imaging OX40+ Activated T Cells Provides Early Warning of Rheumatoid Arthritis.

PURPOSE: The goal of this study was to develop an imaging probe-IRDye-680RD-OX40 mAb-that can be used for noninvasive imaging and optical imaging of rheumatoid arthritis (RA). OX40/OX40 ligand (OX40L) interactions have been shown to exert potent costimulatory effects on T cell activation. Detectable change in T cell activation profiles was observed in early RA. METHODS: OX40 expression pattern was analyzed by flow cytometry. N-hydroxysuccinimide (NHS) esters are used to label proteins selectively on free amino groups of OX40 monoclonal antibody (mAb). Characterization of IRDye-680RD-OX40 mAb was measured and a fluorescence spectrum gathered. Cell binding assay was also performed between activated and naïve murine T cells. Longitudinal near-infrared fluorescence (NIRF) imaging of the probe was performed on day 8, day 9, day 10, and day 11 of adjuvant-induced arthritis (AIA) mouse model. Paw thickness and body weight were compared between the OX40 mAb and IgG injection groups. RESULTS: NIRF imaging with IRDye-680RD-OX40 mAb revealed strong OX40-positive responses with high specificity. Flow analysis showed that OX40 was specifically expressed on the surface of T cells in RP and spleen of AIA model. The AIA group was significantly differentiated from the control group at all time points with imaging monitoring. The region of interest (ROI) was in line with ex vivo imaging and biodistribution study. This study highlights the potential utility of the OX40 NIRF imaging as a new strategy for RA prediction and T cell monitoring. CONCLUSION: The results provide evidence that IRDye-680RD-OX40 mAb detects organized T cells activation in early RA. The optical probe was capable of detection of RA pathogenesis. It identified transcriptional responses to RA that mediate its immune functions. Thus, it may be an ideal probe for RA imaging.

Bifunctional Interface Passivation via Copper Acetylacetonate for Efficient and Stable Perovskite Solar Cells.

Manipulating interface defects can minimize interfacial nonradiative recombination, thus increasing the stability and performance of perovskite solar cells (PSCs). Here, copper acetylacetonate [Cu(acac)2] as a passivator is used to treat the interface between Spiro-OMeTAD and perovskite. Owing to the strong chelation, the uncoordinated Pb2+ could react with -C═O/-COH functional groups, firmly anchoring acetylacetonate at this interface or the grain boundaries (GBs) of perovskite films to construct multiple ligand bridges, accompanied by the p-type copper iodide formation with copper substituting lead. Simultaneously, Cu+-Cu2+ pairs transfer electrons from Pb0 to I0, suppressing deep level defects of Pb0 and I0 near the perovskite interface. These can be beneficial to hole-transferring. Moreover, the Schiff base complexes with hydrophobicity, from the reaction of acetylacetonate with perovskite, can lead to tightly packed adjacent perovskite surfaces and self-seal the GBs of the perovskite, inhibiting moisture diffusion for long-term stability. Consequently, the Cu(acac)2-based PSC has achieved more than 24% champion efficiency while retaining ca. 92% of the initial power conversion efficiency after 1680 h of storage.

The protective effects of S14G-humanin (HNG) against mono-sodium urate (MSU) crystals- induced gouty arthritis.

Gout is a common and complex form of arthritis that has brought great inconveniences to the normal lives of patients. It is reported that oxidative stress and nod-like receptor family protein 3 (NLRP3) inflammasome-mediated inflammatory reactions are involved in the pathogenesis of gout arthritis. S14G-humanin (S14G-HNG) is a modified peptide of HNG with higher inhibitory activity on the accumulation and deposition of Aß. Recently, S14G-HNG has been reported to exert great anti-inflammatory effects. The present study proposed to explore the possible therapeutic property of S14G-HNG against gout arthritis. An animal model was established by stimulation with mono-sodium urate (MSU) crystals, followed by treatment with colchicine and S14G-HNG, respectively. The elevated Gait score promoted synovitis score and activated myeloperoxidase (MPO) observed in MSU crystals-treated mice were significantly reversed by colchicine and S14G-HNG. Bone marrow-derived macrophages (BMDMs) were isolated from mice and stimulated with MSU crystals, followed by being treated with 25 and 50 µM S14G-HNG. The increased mitochondrial reactive oxygen species (ROS) and Malondialdehyde (MDA) levels, upregulated NADPH oxidase-4 (NOX-4), activated NLRP3 inflammasome, and elevated production of inflammatory factors in MSU crystals-treated BMDMs were dramatically reversed by S14G-HNG, accompanied by the upregulation of sirtuin type-1 (SIRT1). Lastly, the protective effects of S14G-HNG against MSU crystals-induced NLRP3 inflammasome activation were significantly abolished by the knockdown of SIRT1. In conclusion, our data reveal that S14G-HNG could possess potential benefits against MSU crystals-induced gout arthritis, with colchicine displaying a better effect.

CXCR4 antagonist AMD3100 enhances therapeutic efficacy of transcatheter arterial chemoembolization in rats with hepatocellular carcinoma.

This study aims to discover the therapeutic effect of chemokine (CXC motif) receptor 4 (CXCR4) antagonist AMD3100 combined with transcatheter arterial chemoembolization (TACE) in a rat model with hepatocellular carcinoma (HCC). An orthotopic model of HCC was established and treated with TACE (doxorubicin-lipiodol emulsion) with or without AMD3100. The tumor volume was measured by magnetic resonance imaging (MRI). Histopathological changes were detected by hematoxylin-eosin (HE) staining. HCC cell apoptosis was assessed by terminal deoxyribonucleotidyl transferase (TdT)-mediated biotin-16-dUTP nick-end labeling (TUNEL) staining. Immunohistochemistry was used to detect the expression of CD34, hypoxia-inducible factor 1α (HIF-1α), vascular endothelial growth factor (VEGF), and Ki67. Gene and protein expressions were quantified by quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and western blotting, respectively. Both TACE and AMD3100 reduced the tumor volume in orthotopic rat model of HCC with the decreased CXCR4 expression in tumor tissues, and the combination had better effect. However, TACE increased the microvessel density (MVD) in HCC tissues of rats, while AMD3100 treatment reduced MVD in HCC tissues. AMD3100 reduced the TACE induced MVD in HCC tissues with the reduction of HIF-1α and VEGF expression. Either AMD3100 or TACE could promote HCC cell apoptosis accompanying by decreased cell proliferation, and their combined use had better therapeutic effects. CXCR4 antagonist AMD3100 enhance therapeutic efficacy of TACE in rats with HCC via promoting the HCC cell apoptosis, reducing cell proliferation, and inhibiting MVD, thus reducing tumor volume.

Effects of cinnamon granules on pharmacokinetics of berberine in Rhizoma Coptidis granules in healthy male volunteers.

The effects of Cinnamon granules on pharmacokinetics of berberine in Rhizoma Coptidis granules in healthy male volunteers, and the compatibility mechanism of Jiao-Tai-Wan (JTW) composed of Rhizoma Coptidis granules and Cinnamon granules were investigated. The concentration of berberine in plasma of healthy male volunteers was determined directly by high performance liquid chromatography (HPLC) after an oral administration of Rhizoma Coptidis granules alone or combined with Cinnamon granules (JTW). The plasma concentration-time curves of berberine were plotted. The data were analyzed with Drug and Statistics (DAS) 2.0 pharmacokinetic program (Chinese Pharmacology Society) to obtain the main pharmacokinetic parameters. The results showed that the plasma concentration-time curve of berberine was described by a two-compartment model. The C(max), T(max), t(1/2) and CLz/F of berberine in Rhizoma Coptidis granules were 360.883 µg/L, 2.0 h, 3.882 h, 119.320 L·h(-1)·kg(-1) respectively, and those of berberine in JTW were 396.124 µg/L, 1.5 h, 4.727 h, 57.709 L·h(-1)·kg(-1) respectively. It was suggested that Rhizoma Coptidis granules combined with Cinnamon granules could increase the plasma concentration of berberine, promote berberine absorption and lengthen the detention time of berberine in healthy male volunteers.