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1.
Biochim Biophys Acta Mol Basis Dis ; 1870(7): 167304, 2024 Jun 13.
Article in English | MEDLINE | ID: mdl-38878830

ABSTRACT

Pancreatic cancer (PC) responds weakly to conventional immunotherapy. RNA N6-methyladenosine (m6A) modification has an essential role in the immune response, while its potential role in PC tumor microenvironment (TME) immune cell infiltration remains unknown. In this study, we thoroughly assessed the m6A modification patterns of 472 PC samples using 19 m6A regulators, and we systematically correlated these modification patterns with TME immune cell infiltration characteristics. We also created the m6Ascore and evaluated the m6A modification patterns of individual tumors, identified three different m6A modification patterns, and explored the role of the important m6A "writer" RBM15 in the regulation of macrophage function in PC. Two independent PC cohorts confirmed that patients with higher m6Ascore showed significant survival benefit. We verified that knockdown of RBM15 has the ability to inhibit PC growth and to promote macrophage infiltration and enhance phagocytosis of PC cells by macrophages. In conclusion, m6A modifications play a non-negligible role in the formation of TME diversity and complexity in PC. We reveal that inhibition of RBM15 suppresses PC development and modulates macrophage phagocytosis, and provide a more effective immunotherapeutic strategy for PC.

2.
Discov Oncol ; 14(1): 102, 2023 Jun 15.
Article in English | MEDLINE | ID: mdl-37318676

ABSTRACT

Intrahepatic cholangiocarcinoma (ICC) is a fatal disease and the molecular mechanism of its progression remains unknown. Aurora Kinase B (AURKB) is a central regulator of chromosome separation and cytokinesis and is abnormally expressed in a variety of cancer cells. This research aimed to explore the effect of AURKB in occurrence and metastasis of ICC. We found that AURKB showed a progressive up-regulation pattern from normal bile duct tissue to ICC with high invasion. Our data showed that AURKB significantly promoted ICC cell proliferation, induced epithelial-mesenchymal transition (EMT), migration and invasion through gain- and loss- of function experiments. In vivo results consistently showed that AURKB up-regulation not only promoted tumor growth, but also promoted tumor metastasis. Importantly, we discovered that AURKB regulates the expressions of EMT-related genes via PI3K/AKT signaling axis. Herein, our results suggest that AURKB induced EMT through the activation of PI3K/AKT signaling pathway is critical to the progression of ICC, which may be a prospective therapeutic treatment for overcoming ICC metastasis and progression.

3.
Front Oncol ; 11: 762653, 2021.
Article in English | MEDLINE | ID: mdl-34868978

ABSTRACT

Most randomized trials for acute promyelocytic leukemia (APL) have investigated highly selected patients under idealized conditions, and the findings need to be validated in the real world. We conducted a population-based study of all APL patients in Zhejiang Province, China, with a total population of 82 million people, to assess the generalization of all-trans retinoic acid (ATRA) and arsenic as front-line treatment. The outcomes of APL patients were also analyzed. Between January 2015 and December 2019, 1,233 eligible patients were included in the final analysis. The rate of ATRA and arsenic as front-line treatment increased steadily from 66.2% in 2015 to 83.3% in 2019, with no difference among the size of the center (≥5 or <5 patients per year, p = 0.12) or age (≥60 or <60 years, p = 0.35). The early death (ED) rate, defined as death within 30 days after diagnosis, was 8.2%, and the 3-year overall survival (OS) was 87.9% in the whole patient population. Age (≥60 years) and white blood cell count (>10 × 109/L) were independent risk factors for ED and OS in the multivariate analysis. This population-based study showed that ATRA and arsenic as front-line treatment are widely used under real-world conditions and yield a low ED rate and a high survival rate, which mimic the results from clinical trials, thereby supporting the wider application of APL guidelines in the future.

4.
Chem Commun (Camb) ; 57(64): 7954-7957, 2021 Aug 10.
Article in English | MEDLINE | ID: mdl-34286749

ABSTRACT

Herein, we report, for the first time, a Pd6L8(NO3)5.4(ICG)6.6 (ICG = indocyanine green) cage-based hexagonal nanoplate (3) via a combined nanoprecipitation and solid-state anion-exchange approach. Nanoplate 3 possesses enhanced near-infrared (NIR) light-triggered 1O2 generation, high cellular uptake selective lysosome-targeting ability, and, consequently, excellent antineoplastic activity.


Subject(s)
Antineoplastic Agents/pharmacology , Metal-Organic Frameworks/pharmacology , Nanoparticles/chemistry , Photosensitizing Agents/pharmacology , Antineoplastic Agents/chemistry , Cell Proliferation/drug effects , Drug Screening Assays, Antitumor , Humans , Infrared Rays , MCF-7 Cells , Metal-Organic Frameworks/chemistry , Molecular Structure , Particle Size , Photochemotherapy , Photosensitizing Agents/chemistry
5.
Article in English | MEDLINE | ID: mdl-33548831

ABSTRACT

Pagiophloeus tsushimanus is a new, destructive, and monophagous weevil pest that thrives on Cinnamomum camphora, found in Shanghai. The functions of chemosensory genes involved in the host location and intraspecific communication of P. tsushimanus remain unknown. The male-female transcriptomes of P. tsushimanus adults were assembled using Illumina sequencing, and we focused on all chemosensory genes in transcriptomes. In general, 58,088 unigenes with a mean length of 1018.19 bp were obtained. In total, 39 odorant binding proteins (OBPs), 10 chemosensory proteins (CSPs), 22 olfactory receptors (ORs), 16 gustatory receptors (GRs), eight ionotropic receptors (IRs), and five sensory neuron membrane proteins (SNMPs) were identified. PtsuOBPs comprised four subfamilies (20 Minus-C, one Plus-C, two Dimer, and 15 Classic). Both PtsuOBPs and PtsuCSPs contained a highly conserved sequence motif of cysteine residues. PtsuORs including one olfactory receptor co-receptors (Ptsu/Orco) comprised seven predicted transmembrane domains. Phylogenetic analysis revealed that PtsuOBPs, PtsuCSPs, and PtsuORs in P. tsushimanus exhibited low homology compared to other insect species. The results of tissue- and sex-specific expression patterns indicated that PtsuOBPs and PtsuORs were highly abundant in the antennae; whereas, PtsuCSPs were not only highly abundant in antennae, but also abdominal apexes, wings, and legs. In conclusion, these results enrich the gene database of P. tsushimanus, which may serve as a basis for identifying novel targets to disrupt olfactory key genes and may provide a reverse validation method to identify attractants for formulating potential eco-friendly control strategies for this pest.


Subject(s)
Transcriptome , Weevils/genetics , Animals , Cinnamomum camphora/parasitology , Female , Insect Proteins/genetics , Ligand-Gated Ion Channels/genetics , Male , Membrane Proteins/genetics , Phylogeny , Receptors, Odorant/genetics , Sensory Receptor Cells/metabolism , Weevils/cytology
6.
Nat Prod Res ; 35(9): 1491-1496, 2021 May.
Article in English | MEDLINE | ID: mdl-31429297

ABSTRACT

A phytochemical investigation on the whole plant of Plantago maxima Juss. ex Jacq led to the isolation of a new and rare chlorinated iridoid glycoside named plantomoside (1), along with three known compounds, geniposidic acid (2), 10-deoxygeniposidic acid (3), and viteoid II (4). The structure of 1 was determined through 1 D and 2 D NMR spectroscopic data analysis, HR-ESI-MS, and acid hydrolysis.


Subject(s)
Chlorine/chemistry , Iridoid Glycosides/isolation & purification , Plantago/chemistry , Animals , Cell Death/drug effects , Cell Line, Tumor , Humans , Iridoid Glucosides/chemistry , Iridoid Glucosides/isolation & purification , Iridoid Glycosides/chemistry , Iridoid Glycosides/pharmacology , Lipopolysaccharides/pharmacology , Mice , Nitric Oxide/biosynthesis , Phytochemicals/chemistry , Phytochemicals/isolation & purification , Phytochemicals/pharmacology , RAW 264.7 Cells
7.
Ann Transl Med ; 8(8): 530, 2020 Apr.
Article in English | MEDLINE | ID: mdl-32411753

ABSTRACT

BACKGROUND: Hyperphosphatemia is a common complication of late-stage chronic kidney disease (CKD). Nicotinamide (NAM) has been reported as an adjunctive therapy for hyperphosphatasemia, but the effect of NAM on fibroblast growth factor 23 (FGF23) and Klotho has rarely been reported. METHODS: We randomly assigned 98 patients who underwent regular hemodialysis to received NAM (0.5-1.5 g per day, or 1-3 tablets per day) or placebo (1-3 tablets per day) as an add-on therapy of calcium-based phosphorus binders in a 1:1 ratio. All enrollments were followed-up for 52 weeks. We investigated the serum phosphorus as the primary outcome and serum FGF23 and Klotho as the secondary outcomes. Abdominal aortic calcification (AAC), which had a good correlation with coronary calcification was also compared between the two groups. RESULTS: In total, 37 patients in the placebo group and 35 patients in the NAM group completed the 52-week follow-up. Compared with the placebo group, the NAM group showed a significant decrease of serum phosphorus at the 8th, 12th, 20th, 44th, and 52nd week. There was a declining trend of FGF23 and Klotho in both the placebo and NAM groups. Linear mixed models (LMMs) for overall comparisons by repeated measures of analysis of variance (ANOVA) revealed a significant decrease of FGF23 and slower declining rate of Klotho in the NAM group. No significant difference of AAC was detected between the two groups (P=0.805). CONCLUSIONS: NAM can not only further decrease the phosphorus level but also reduce the FGF23 level and slow down the descending rate of Klotho in chronic hemodialysis patients.

8.
Cytotherapy ; 21(11): 1122-1136, 2019 11.
Article in English | MEDLINE | ID: mdl-31699595

ABSTRACT

Systemic chemotherapy is a conventional and important strategy for inhibition of cancer progression, but it is usually accompanied by various adverse effects. Targeting drug delivery systems, effective tools to avoid the adverse effects of chemotherapy, have been intensively studied and developed. Recently, the emerging application of exosomes and exosome-mimics (small extracellular vesicles [sEVs]) in targeted drug delivery and therapeutics has been widely appreciated. The sEVs-based delivery system comprises three basic components: vesicles, cargoes and surface decorations. In this article, we review the current status, existing challenges and future directions in this field from the following aspects: selection and production of vesicles; cargoes and methods to load them into vesicles; modifications to the surfaces of vesicles; as well as ways to prolong the half-life of sEVs in the circulation. Existing and emerging data indicate that sEVs are promising nanocarriers for clinical use, but additional efforts are needed to translate research findings into therapeutic products.


Subject(s)
Drug Delivery Systems/methods , Extracellular Vesicles/metabolism , Medical Oncology/trends , Neoplasms/therapy , Animals , Drug Compounding/methods , Drug Compounding/trends , Exosomes/physiology , Exosomes/transplantation , Extracellular Vesicles/physiology , Humans , Medical Oncology/methods
9.
J Cancer ; 10(18): 4397-4407, 2019.
Article in English | MEDLINE | ID: mdl-31413760

ABSTRACT

Cancer-associated fibroblasts (CAFs), which are an important component of the tumor microenvironment, have been identified in the blood circulation of patients with cancer metastasis, and metastatic cancer cells can recruit circulating CAFs. However, primary carcinoma sites usually regulate the behavior of metastatic cancer cells through exosomes. Here, we hypothesized that cancer-derived exosomes could enhance CAF recruitment. Exosomes secreted by pancreatic cancer cells (PANC-1 and MIA PaCa-2) were isolated and characterized. The ability of pancreatic cancer to recruit pancreatic stellate cells (PSCs) was assessed with Transwell assays in vitro and bioluminescent imaging in a mouse model in vivo, and the underlying molecular mechanism was also investigated. The results showed that pancreatic cancer cell-derived exosomes (Exo-Pan and Exo-Mia) promoted the pancreatic cancer recruitment of PSCs. This effect was mediated partially by the transfer of the exosomal protein Lin28B to the recipient cells to activate the Lin28B/let-7/HMGA2/PDGFB signaling pathway. These results suggested that exosomes derived from local cancer could promote the formation of distant metastases through transferring the exosomal protein Lin28B to the metastatic cancer cells.

10.
Front Pharmacol ; 10: 832, 2019.
Article in English | MEDLINE | ID: mdl-31404235

ABSTRACT

Lamotrigine (LTG) is a second-generation anti-epileptic drug widely used for focal and generalized seizures in adults and children, and as a first-line medication in pregnant women and women of childbearing age. However, LTG pharmacokinetics shows high inter-individual variability, thus potentially leading to therapeutic failure or side effects in patients. This prospective study aimed to establish a population pharmacokinetics model for LTG in Chinese patients with epilepsy and to investigate the effects of genetic variants in uridine diphosphate glucuronosyltransferase (UGT) 1A4, UGT2B7, MDR1, ABCG2, ABCC2, and SLC22A1, as well as non-genetic factors, on LTG pharmacokinetics. The study population consisted of 89 patients with epilepsy, with 419 concentrations of LTG. A nonlinear mixed effects model was implemented in NONMEM software. A one-compartment model with first-order input and first-order elimination was found to adequately characterize LTG concentration. The population estimates of the apparent volume of distribution (V/F) and apparent clearance (CL/F) were 12.7 L and 1.12 L/h, respectively. The use of valproic acid decreased CL/F by 38.5%, whereas the co-administration of rifampicin caused an increase in CL/F of 64.7%. The CL/F decreased by 52.5% in SLC22A1-1222AA carriers. Patients with the ABCG2-34AA genotype had a 42.0% decrease in V/F, whereas patients with the MDR1-2677TT and C3435TT genotypes had a 136% increase in V/F. No obvious genetic effect of UGT enzymes was found relative to the concentrations of LTG in Chinese patients. Recommended dose regimens for patients with different gene polymorphisms and comedications were estimated on the basis of Monte Carlo simulations and the established model. These findings should be valuable for developing individualized dosage regimens in adult and adolescent Chinese patients 13-65 years of age.

11.
Clin Lab ; 65(1)2019 Jan 01.
Article in English | MEDLINE | ID: mdl-30775888

ABSTRACT

BACKGROUND: In order to increase the detection rate of pathogenic microorganisms in CSF, an improved specimen handling procedure (ISHP) was created. METHODS: This study enrolled encephalitis and control groups, both groups were handled with traditional specimen handling procedure (TSHP) and ISHP. Glutaraldehyde was added to the ISHP. Observed items included: total protein, glucose, chloride, adenosine deaminase, lactate dehydrogenase, sediment, cell and pathogen, Pandy's test. RESULTS: Sediment test of CSF: There was 1 specimen in 10 control specimens tested by TSHP in which Pandy's test was positive; there were 2 specimens tested by ISHP which could see sediment by eye. There was no statistical difference between those two methods (p = 1.000, Table 1). Ten specimens in 23 of the encephalitis group processed by TSHP were positive with Pandy's test; 23 specimens processed by ISHP could all see sediments by eye (Figure 1). There was a statistical difference between the two methods (p = 0.000, Table 1). Pathogen test of CSF: no pathogen was found in the control group processed by TSHP and ISHP. No pathogen was found in the encephalitis group specimens processed by TSHP. Pathogen tests were positive in 7 encephalitis specimens processed by ISHP (p = 0.009, Table 1), which were confirmed as Rickettsia spp. by Gimenze stain (Figure 1B), IFA (Figure 2). CONCLUSIONS: The results revealed that ISHP contributes to the separation of cells, pathogens (such as Rickettsia), and proteins.


Subject(s)
Infectious Encephalitis/cerebrospinal fluid , Rickettsia Infections/cerebrospinal fluid , Rickettsia/physiology , Specimen Handling/methods , Adolescent , Adult , Aged , Aged, 80 and over , Child , Female , Humans , Infectious Encephalitis/diagnosis , Infectious Encephalitis/microbiology , Male , Microscopy, Fluorescence , Middle Aged , Rickettsia Infections/diagnosis , Rickettsia Infections/microbiology , Young Adult
12.
J Invest Surg ; 32(1): 27-34, 2019 Jan.
Article in English | MEDLINE | ID: mdl-28985095

ABSTRACT

OBJECTIVE: The aim of this study was to compare the efficacy between SBRT and surgery based on the Propensity-Matched Analysis. METHODS: Publications on comparison SBRT and Surgery for early stage non- small cell lung cancer (NSCLC) from 2011 to 2017 were collected. Propensity score matching was used to achieve comparable treatment hazard ratios of the overall survival (OS), local control survival (LC), regional control survival (RC), loco-regional control survival (LRC), distant control survival (DC), disease-free survival (DFS), and progression-free survival (PFS) between SBRT and Surgery. The major outcomes measures were hazard ratios (HRs). Meta-analysis Revman 5.3 software was used to analyze the combined Pooled HRs using fixed- or random-effects models according to the heterogeneity. RESULT: Eleven studies met our inclusion criteria. The LC, L-R C, DC, DFS and PFS rates of patients with early-stage lung cancer who were treated with SBRT are equal to surgical results. While, patients with surgery achieved superior OS compared with SBRT. CONCLUSION: In this study we carried out a meta-analysis, which controls the acceptable level of the efficacy in the propensity score to match patients. The surgery had obvious OS advantages in this meta-analysis. However, these conclusions would be proven by further studies incorporating comorbidity data, and outcomes from randomized control study. The final decision for the optimal treatment of a patient with early-stage NSCLC can be substantiated by a personalized treatment model.


Subject(s)
Carcinoma, Non-Small-Cell Lung/therapy , Lung Neoplasms/therapy , Neoplasm Recurrence, Local/epidemiology , Pneumonectomy , Radiosurgery , Carcinoma, Non-Small-Cell Lung/mortality , Carcinoma, Non-Small-Cell Lung/pathology , Disease-Free Survival , Humans , Lung Neoplasms/mortality , Lung Neoplasms/pathology , Neoplasm Recurrence, Local/prevention & control , Neoplasm Staging , Progression-Free Survival , Propensity Score
13.
Dig Dis Sci ; 63(9): 2285-2293, 2018 09.
Article in English | MEDLINE | ID: mdl-29781054

ABSTRACT

BACKGROUND: This study was designed to explore the anticancer potential of isoalantolactone, a sesquiterpene lactone, on esophageal squamous cell carcinoma (ESCC) cells and associated molecular mechanisms. METHODS: ESCC cell lines were treated with isoalantolactone or vehicle and tested for viability, proliferation, cell cycle distribution, and apoptosis. Xenograft tumor studies in nude mice were done to examine the in vivo anticancer effect of isoalantolactone. RESULTS: Isoalantolactone treatment reduced ESCC cell viability and proliferation in vitro, which was coupled with induction of G0/G1 cell cycle arrest and apoptosis. In vivo studies confirmed the growth-suppressive effect of isoalantolactone on ESCC cells. Mechanistically, isoalantolactone reversed microRNA-21-mediated repression of programmed cell death 4 (PDCD4). Overexpression of microRNA-21 and knockdown of PDCD4 blocked the growth suppression and apoptosis induction by isoalantolactone in ESCC cells. CONCLUSIONS: Isoalantolactone shows growth-suppressive activity against ESCC cells, which is ascribed to upregulation of PDCD4 via downregulation of microRNA-21.


Subject(s)
Antineoplastic Agents/pharmacology , Apoptosis Regulatory Proteins/metabolism , Carcinoma, Squamous Cell/drug therapy , Cell Proliferation/drug effects , Esophageal Neoplasms/drug therapy , MicroRNAs/metabolism , RNA-Binding Proteins/metabolism , Sesquiterpenes/pharmacology , Animals , Apoptosis/drug effects , Apoptosis Regulatory Proteins/genetics , Carcinoma, Squamous Cell/enzymology , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/pathology , Cell Cycle Checkpoints/drug effects , Cell Line, Tumor , Dose-Response Relationship, Drug , Down-Regulation , Esophageal Neoplasms/enzymology , Esophageal Neoplasms/genetics , Esophageal Neoplasms/pathology , Esophageal Squamous Cell Carcinoma , Gene Expression Regulation, Neoplastic , Humans , Male , Mice, Inbred BALB C , Mice, Nude , MicroRNAs/genetics , RNA-Binding Proteins/genetics , Signal Transduction/drug effects , Time Factors , Tumor Burden/drug effects , Xenograft Model Antitumor Assays
14.
Eur J Clin Pharmacol ; 74(1): 61-67, 2018 Jan.
Article in English | MEDLINE | ID: mdl-28975417

ABSTRACT

PURPOSE: The purpose of this study was to investigate the potential effects of a meal and grapefruit juice on the pharmacokinetics of blonanserin and its metabolite N-desethyl blonanserin in healthy Chinese volunteers. METHODS: This was a single-centre, open-label, fixed-sequence study, where 12 healthy Chinese volunteers received a single dose of 8 mg blonanserin after an overnight fast in period 1 (reference), a high-fat meal during period 2 and with co-administration of 250 mL of grapefruit juice in period 3. The washout period was 7 days. Series of plasma samples were collected after each dose to determine concentrations of blonanserin and its metabolite N-desethyl blonanserin using liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters were estimated by non-compartmental analysis and compared between periods by standard average bioequivalence ANOVA. Adverse events were monitored throughout the study. RESULTS: All subjects completed the study. High-fat meals significantly increased blonanserin exposure (AUCt) 2.58-fold (90% CI 2.21, 3.02), relative to the reference period. Co-administration of blonanserin with grapefruit juice remarkably prolonged elimination half-life of blonanserin (from 9.7 to 21.4 h) and significantly increased exposures to blonanserin and N-desethyl blonanserin by 5.82-fold (90% CI 4.57, 7.42) and 1.81-fold (90% CI 1.65, 1.98), respectively. CONCLUSIONS: These results suggested that blonanserin was largely metabolised in the intestinal tract before becoming systemically available, and both food and grapefruit juice enhanced exposure to blonanserin and N-desethyl blonanserin. Grapefruit juice increased bioavailability and may have reduced systemic clearance of blonanserin. Further intestinal CYP3A4 and hepatic CYP3A4 might be postulated to explain the delayed elimination of blonanserin. Dose adjustment of blonanserin is needed on the basis of co-intake of known strong CYP3A4 inhibitor. Patients taking high-dose blonanserin also need to be cautious about the ingestion of grapefruit juice.


Subject(s)
Citrus paradisi , Food-Drug Interactions , Fruit and Vegetable Juices , Piperazines/blood , Piperidines/blood , Adult , Area Under Curve , Biological Availability , Cytochrome P-450 CYP3A/metabolism , Dose-Response Relationship, Drug , Healthy Volunteers , Humans , Intestines/enzymology , Male , Piperazines/administration & dosage , Piperidines/administration & dosage , Young Adult
15.
Tumour Biol ; 39(3): 1010428317695971, 2017 Mar.
Article in English | MEDLINE | ID: mdl-28347229

ABSTRACT

The aim of this study was to investigate the role of G-protein signaling modulator 2 in the carcinogenesis and progression of hepatocellular carcinoma. We previously showed that G-protein signaling modulator 2 was upregulated in hepatitis B virus-related hepatocellular carcinoma tissues through a hierarchical clustering analysis. With this study, we first assessed the expression pattern of G-protein signaling modulator 2 in hepatocellular carcinoma specimens and adjacent noncancerous tissues; clinical data were analyzed, along survival times, utilizing the Kaplan-Meier method. Moreover, the functions of G-protein signaling modulator 2 were examined using small-interfering RNAs in vitro. The results showed that G-protein signaling modulator 2 was clearly overexpressed in hepatocellular carcinoma tissues and cell lines and that the G-protein signaling modulator 2 expression level was related to tumor size and hepatitis B virus infection. Furthermore, G-protein signaling modulator 2 knockdown studies suggested that G-protein signaling modulator 2 accelerates cell growth, cell cycle, migration, and invasion and inhibits apoptosis, acting as an oncogene in hepatocellular carcinoma. Western blotting indicated that silencing of G-protein signaling modulator 2 in HepG2 and SMMC-7721 cells increased the expression levels of Bax, caspase-3, and E-cadherin, while notably suppressing the cyclin-dependent kinase 4, cyclin-dependent kinase 6, CyclinD1, Snail1, Vimentin, and matrix metallopeptidase 9 expression levels, compared with that in the control groups. In addition, we found that G-protein signaling modulator 2 can affect the expression of key proteins involved in protein kinase B activation. In conclusion, high expression of G-protein signaling modulator 2 was involved in the pathological processes of hepatocellular carcinoma through activation of the phosphatidylinositol 3-kinase/protein kinase B signaling pathway, which may provide an attractive potential diagnostic biomarker and therapeutic target for treatment of hepatocellular carcinoma.


Subject(s)
Carcinoma, Hepatocellular/genetics , Intracellular Signaling Peptides and Proteins/biosynthesis , Liver Neoplasms/genetics , Neoplasm Proteins/biosynthesis , Adult , Aged , Apoptosis/genetics , Carcinoma, Hepatocellular/pathology , Cell Cycle/genetics , Cell Movement/genetics , Cell Proliferation/genetics , Female , Gene Expression Regulation, Neoplastic , Hep G2 Cells , Humans , Intracellular Signaling Peptides and Proteins/genetics , Liver Neoplasms/pathology , Male , Middle Aged , Neoplasm Invasiveness/genetics , Neoplasm Invasiveness/pathology , Neoplasm Metastasis , Neoplasm Proteins/genetics , Phosphatidylinositol 3-Kinase/genetics , Proto-Oncogene Proteins c-akt/genetics , Signal Transduction
16.
Clin Drug Investig ; 36(9): 705-711, 2016 Sep.
Article in English | MEDLINE | ID: mdl-27317305

ABSTRACT

BACKGROUND AND OBJECTIVES: Peramivir, an antiviral agent for intravenous administration, is used to treat progressive influenza in patients with serious complications. The present study was designed to determine the pharmacokinetics of single and multiple intravenous infusions of peramivir in healthy Chinese subjects. METHODS: Single (150, 300 and 600 mg) and multiple (600 mg) doses of peramivir were intravenously administered to 12 healthy Chinese subjects. There was a 7-day washout period between dosing periods. Blood samples were collected in heparinized tubes at various times. Plasma peramivir and urine peramivir concentrations were measured using a high-performance liquid chromatography-tandem mass spectrometry method. RESULTS: Following single doses of peramivir (150, 300 and 600 mg), the maximum concentration (C max) values were 12,416 ± 3078, 23,147 ± 3668 and 44,113 ± 3787 µg/L, respectively, and the area under the plasma concentration-time curve (AUC) from 0 h to infinity post-dose (AUC∞) values were 24.68 ± 6.48, 47.33 ± 9.22 and 92.43 ± 12.72 mg·h/L, respectively. C max, AUC from 0 to 36 h (AUC0-36) and AUC∞ of peramivir increased proportionally with the dose, and no trend towards accumulation after multiple doses was observed. About 65 % of the peramivir was excreted unchanged in the urine within the first 24 h. CONCLUSIONS: Peramivir pharmacokinetics were dose proportional with increasing doses, with no accumulation after multiple dosing. Peramivir was generally well tolerated, and no serious adverse events occurred.


Subject(s)
Antiviral Agents/pharmacokinetics , Cyclopentanes/pharmacokinetics , Guanidines/pharmacokinetics , Acids, Carbocyclic , Adolescent , Adult , Antiviral Agents/administration & dosage , Antiviral Agents/urine , Area Under Curve , Asian People , Biotransformation , Chromatography, High Pressure Liquid , Cyclopentanes/administration & dosage , Cyclopentanes/urine , Female , Guanidines/administration & dosage , Guanidines/urine , Healthy Volunteers , Humans , Infusions, Intravenous , Male , Tandem Mass Spectrometry , Young Adult
17.
Lung ; 193(4): 583-92, 2015 Aug.
Article in English | MEDLINE | ID: mdl-25851596

ABSTRACT

BACKGROUND: Non-small-cell lung cancer (NSCLC), the most common lung cancer, leads to the largest number of cancer-related deaths worldwide. There are many studies to identify the differentially expressed genes (DEGs) between NSCLC and normal control (NC) tissues by means of microarray technology. Because of the inconsistency of the microarray data sets, we performed an integrated analysis to identify DEGs and analyzed their biological function. METHODS AND RESULTS: We combined 15 microarray data sets and identified 1063 DEGs between NSCLC and NC tissues; in addition, we found that the DEGs were enriched in regulation of cell proliferation process and focal adhesion signaling pathway. The protein-protein interaction network analysis for the top 20 significantly DEGs revealed that CAV1, COL1A1, and ADRB2 were the significant hub proteins. Finally, we employed qRT-PCR to validate the meta-analysis approach by determining the expression of the top 10 most significantly DEGs and found that the expression of these genes were significantly different between tumor and NC tissues, in accordance with the results of meta-analysis. CONCLUSION: qRT-PCR results indicated that the meta-analysis approach in our study was acceptable. Our data suggested that some of the DEGs, including MMP12, COL11A1, THBS2, FAP, and CAV1, may participate in the pathology of NSCLC and could be applied as potential markers or therapeutic targets for NSCLC.


Subject(s)
Carcinoma, Non-Small-Cell Lung/genetics , Lung Neoplasms/genetics , Lung/chemistry , Caveolin 1/genetics , Cell Adhesion/genetics , Cell Proliferation/genetics , Collagen Type I/genetics , Collagen Type I, alpha 1 Chain , Gene Expression Profiling , Humans , Real-Time Polymerase Chain Reaction , Receptors, Adrenergic, beta-2/genetics , Signal Transduction , Tissue Array Analysis
18.
Int J Syst Evol Microbiol ; 65(Pt 5): 1587-1591, 2015 May.
Article in English | MEDLINE | ID: mdl-25713037

ABSTRACT

A novel actinomycete strain, designated TRM 45387(T), was isolated from a saline-alkali soil in Xinjiang Province (40° 22' N 79° 08' E), north-west China. The isolate was characterized using a polyphasic approach. 16S rRNA gene sequence analysis indicated that strain TRM 45387(T) belonged to the genus Glycomyces and was closely related to Glycomyces arizonensis DSM 44726(T) (96.59% 16S rRNA gene sequence similarity). The G+C content of the DNA was 71.26 mol%. The isolate contained meso-diaminopimelic acid as the diagnostic diamino acid, and xylose, glucose, galactose, arabinose and ribose as the major whole-cell sugars. The diagnostic phospholipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol and phosphatidylinositolmannosides. The predominant menaquinone was MK-10(H6). The major fatty acids were iso-C16 : 0, anteiso-C17 : 0 and anteiso-C15 : 0. On the basis of the evidence from this polyphasic study, a novel species, Glycomyces tarimensis sp. nov., is proposed. The type strain of Glycomyces tarimensis is TRM 45387(T) ( =CCTCC AA 2014007(T) =JCM 30184(T)).


Subject(s)
Actinomycetales/classification , Phylogeny , Soil Microbiology , Actinomycetales/genetics , Actinomycetales/isolation & purification , Alkalies , Base Composition , China , DNA, Bacterial/genetics , Diaminopimelic Acid/chemistry , Fatty Acids/chemistry , Molecular Sequence Data , Phospholipids/chemistry , RNA, Ribosomal, 16S/genetics , Salinity , Sequence Analysis, DNA , Vitamin K 2/chemistry
19.
Int J Clin Exp Med ; 8(10): 18130-6, 2015.
Article in English | MEDLINE | ID: mdl-26770410

ABSTRACT

Massive cryptogenic hemoptysis is a common presenting symptom and cause of hospitalization for respiratory diseases, and represents a challenging condition in the clinical. This study aimed to analyze the clinical and pathologic data and management of patients with massive cryptogenic hemoptysis. We retrospectively reviewed 12 patients with massive cryptogenic hemotysis in our hospital between January 2003 and December 2012. Bronchoscopy showed submucosal vascular abnormalities in 4 patients. Of 6 patients managed with conservative measures, bleeding was completely controlled in 2 patients. Of 10 hemoptysis patients, three were controlled by bronchial arterial embolization, and seven by surgery. Pathological examination showed a superficial dysplastic, tortuous and dilated bronchial artery under the bronchial epithelium in 4 patients, and bronchiole dilation in 2 patients, indicating Dieulafoy's disease of the bronchus and bronchiectasis. No malignance developed within the follow-up. In conclusion, Dieulafoy's disease of the bronchus and bronchiectasis should be suspected in patients with massive cryptogenic hemoptysis. BAE and surgical treatment should be considered in case that massive hemoptysis could not be controlled by conservative management.

20.
Int J Syst Evol Microbiol ; 64(Pt 10): 3532-3537, 2014 Oct.
Article in English | MEDLINE | ID: mdl-25061064

ABSTRACT

A novel actinomycete strain, designated TRM 45123(T), was isolated from a hypersaline habitat in Xinjiang Province (40° 20' N 90° 49' E), north-west China. The isolate was characterized using a polyphasic approach. 16S rRNA gene sequence analysis indicated that strain TRM 45123(T) belonged to the genus Saccharopolyspora and was closely related to Saccharopolyspora gloriosae (96.7% similarity). The G+C content of the DNA was 69.07 mol%. The isolate contained meso-diaminopimelic acid as the diagnostic diamino acid, and arabinose and ribose as the major whole-cell sugars. The diagnostic phospholipids were phosphatidylethanolamine, phosphatidylcholine and phosphatidylglycerol. The predominant menaquinone was MK-9(H4). The major fatty acids were iso-C16 : 0, anteiso-C17:0, iso-C15:0 and anteiso-C15:0. On the basis of the evidence from this polyphasic study, a novel species, Saccharopolyspora halotolerans sp. nov., is proposed. The type strain of Saccharopolyspora halotolerans is TRM 45123(T) ( = CCTCC AA 2013006(T) = DSM 45990(T)).


Subject(s)
Lakes/microbiology , Phylogeny , Saccharopolyspora/classification , Water Microbiology , Bacterial Typing Techniques , Base Composition , China , DNA, Bacterial/genetics , Diaminopimelic Acid/chemistry , Ecosystem , Fatty Acids/chemistry , Molecular Sequence Data , Phospholipids/chemistry , RNA, Ribosomal, 16S/genetics , Saccharopolyspora/genetics , Saccharopolyspora/isolation & purification , Salinity , Sequence Analysis, DNA , Vitamin K 2/analogs & derivatives , Vitamin K 2/chemistry
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