Adolescent ; Adult ; Eye Injuries ; epidemiology ; etiology ; therapy ; Facility Design and Construction ; Female ; Humans ; Male ; Middle Aged ; Occupational Exposure ; Retrospective Studies ; Visual Acuity

Benzoates ; urine ; Gas Chromatography-Mass Spectrometry ; methods ; Humans

The lipids present in hepatic stellate cells (HSCs) lipid droplets include retinyl ester, triglyceride, cholesteryl ester, cholesterol, phospholipids and free fatty acids. Activation of HSCs is crucial to the development of fibrosis in liver disease. During activation, HSCs transform into myofibroblasts with concomitant loss of their lipid droplets and production of excessive extracellular matrix. Release of lipid droplets containing retinyl esters and triglyceride is a defining feature of activated HSCs. Accumulating evidence supports the proposal that recovering the accumulation of lipids would inhibit the activation of HSCs. In healthy liver, quiescent HSCs store 80%of total liver retinols and release them depending on the extracellular retinol status. However, in injured liver activated HSCs lose their retinols and produce a considerable amount of extracellular matrix, subsequently leading to liver fibrosis. Further findings prove that lipid metabolism of HSCs is closely associated with its activation, yet relationship between activated HSCs and the lipid metabolism has remained mysterious.

The fragmentation pathways of two taxanes drugs have been studied in positive ion mode by Q-TOF with the advantages of high mass accuracy and high resolution analysis. The [M+H] + ions were observed by ESI-MS, from which the molecular weights were obtained. Using the protonated pseudo-molecular ions [M+H]+ as internal reference compounds, the accurate mass and element composition of the fragment ions were determined. The collision induced dissociation (CID) data of the [M+H] ions provided fragmentation pathways of related compounds. Results showed that the major cleavage pathways of paclitaxel and docetaxel were the same that the cleavage of C-O bond between the side chain and taxol skeleton easily occurred, then stripping of the functional groups on the parent ring. Some common fragments were formed, such as m/z 105.033 7, 291.137 3, 309.148 5, 327.159 7, 387.181 2 and 509.217 4, which would provide a basis for future qualitative and quantitative analysis of taxanes in vitro and in vivo.
Paclitaxel ; chemistry ; Peptide Fragments ; chemistry ; Spectrometry, Mass, Electrospray Ionization ; methods ; Taxoids ; chemistry

Background Diabetic retinopathy (DR) leads to blindness because of the retinal angiogenesis caused by the ischemia of retina.Vascular endothelial growth inhibitor (VEGI) is a recently identified anti-angiogenic cytokine,which can suppress endothelial cell proliferation and angiogenesis.Objective The aim of this study was to detect the change of serum and vitreous VEGI/TL1A and its relative cytokines in patients with DR.Methods A non-randomized controlled clinical trial was performed.Fifty-five DR patients were enrolled in Tianjin Medical University General Hospital from November 2012 to March 2013 with the informed consent.The patients were divided into non-proliferative DR (NPDR) group (20 cases) and PDR group (35 cases).Eleven cataract patients served as normal control group,and 15 patients with diabetic mellitus (DM) were included as DM group.The demography was matched among the groups,but the course of DM and the blood glucose level were elevated in the PDR group and the DM group compared with DR group (all at P＜0.05).We collected the serum of all the patients above.Another 23 PDR patients (25 eyes) were enrolled in Tianjin Medical University General Hospital from November 2012 to March 2013 with the informed consent and served as PDR group,healthy corpse's eyes (n=7) as control group,the patients were assigned to the retinal photocoagulation group,surgery group and photocoagulation +surgery group according to different treatment procedures.Vitreous samples were collected during the progress of vitrectomy.TL1A/VEGI 251,VEGF,TNF-α,IL-1β and NF-κB p65 concentrations in the serum and vitreous specimens were detected using ELISA.The differences of serum and vitreous TL1A/VEGI 251,VEGF,TNF-α,IL-1β and NF-κB p65 in various groups were statistically analyzed by ANOVA and independent sample t test,respectively.The correlation between TL1A/VEGI 251 and VEGF,TNF-α,IL-1β,NF-κB p65 were calculated by Pearson correlation analysis.Results TL1A/VEGI 251 concentration was elevated in the DM group,NPDR group and PDR group compared with the normal control group,with significant difference among the 4 group (F =27.431,P =0.009),and TL1A/VEGI 251 concentration was higher in the PDR group than that in the DM group or the NPDR group (P＜0.05).VEGF,TNF-α,IL-1 β and NF-κB p65 concentrations in serum were increased in the PDR group in comparison with the DM group,NPDR group and the normal control group (P＜0.05).However,no significant difference among the DM group,NPDR group and the normal control group (P＞0.05).Serum TL1A/VEGI 251 concentration was significant correlated with VEGF,TNF-α,IL-1β and NF-κB p65 concentration (r=0.951,0.951,0.851,0.944,all at P＜0.01).Vitreous TL1A/VEGI 251,VEGF,TNF-α,IL-1 β concentrations were ascended in the PDR group compared with the normal control group (P =0.024,0.001,0.000,0.037),but there was no significantly difference in vitreous NF-κB p65 concentration between the two groups (P =0.073).Vitreous TL1A/VEGI 251 concentrations declined in the retinal photocoagulation group and the surgery group compared with the normal group (all at P＜ 0.05),and significant positive correlations were found between vitreous TL1A/VEGI 251 concentration and VEGF or TNF-α concentration (r =0.675,0.950,P ＜ 0.01) ;while Pearson correlation coefficient was not statistically significant between vitreous TL1A/VEGI 251 concentration and IL-1β or NF-κB p65 concentration (r=0.233,0.318,P＞0.05).Conclusions VEGI is involved in the pathogenesis of DR,and it interacts with VEGF,TNF-α,IL-1β and NF-κB to affect the development of DR.These results provide a new clue for the further study of DR.

Pro-inflammatory macrophages play key regulatory role in the occurrence and development of rheumatoid arthritis (RA). In this study, we constructed a celastrol (Cel)-loaded polyamide-amine dendrimer (PAMAM) drug delivery system, which could target folate receptor and mitochondria. It could target inflammatory macrophages and realize chemo-photothermal synergistic therapy. Using PAMAM as the nano-carrier, folate receptor-targeting group folic acid (FA) and mitochondria-targeting group IR808 (also known as the photothermal agent) were conjugated with PAMAM through amide reaction, and then complexed with anti-inflammatory drug Cel to prepare the FA-PAMAM-IR808/Cel nanocomplex. In vitro characterization results showed that the drug loading efficiency of the nanocomplex was 50.90%, particle size was between 130 and 160 nm, average potential was between 1.0 and 3.5 mV, the drug release showed pH sensitivity, temperature reached to 42.5 ℃ after near-infrared (NIR) light irradiation for 10 min. In vitro cellular uptake experiments showed that the nanocomplex had obvious folate receptor-targeting and mitochondria-targeting ability. Following irradiation with NIR light, the cytotoxicity and cellular apoptosis enhanced. The secretion of pro-inflammatory factors tumor necrosis factor α (TNF-α), interleukin (IL)-1β, IL-6 and nitric oxide (NO) decreased in a concentration-dependent manner. This study provided insights for the development of novel anti-RA nanomedicines.

OBJECTIVETo study the acute toxicity of the water extracts (ERWE) and 60% ethanol extracts (EREE) from different processed products of Radix Polygalae (crude Radix Polygalae, licorice, and honey processed Radix Polygalae), thus providing scientific evidence for toxicity study of Radix Polygalae and its safe clinical application.

METHODSThe ERWE and EREE were prepared from different processed products of Radix Polygalae. Their contents of saponins were respectively determined. The poisoning condition and death of the mice administered with ERWE and EREE by gastrogavage were observed within fourteen days. The modified Karber's method was used to calculate LD50 and 95% confidence interval (CI).

RESULTSThe EREE of licorice processed Radix Polygalae had the maximum toxicity with highest content of saponins, while the ERWE of honey processed Radix Polygalae had the minimum toxicity with lowest content of saponins.

CONCLUSIONSDifferent processing methods have effects on the contents of saponins in Radix Polygalae. The experiment showed that the toxicity of Radix Polygalae is in direct proportion to the content of saponins. The higher the saponins contents, the higher the toxicity.

Animals ; Female ; Lethal Dose 50 ; Male ; Mice ; Mice, Inbred Strains ; Plant Extracts ; toxicity ; Polygala ; Saponins ; toxicity ; Toxicity Tests, Acute

The aim of this study was to investigate the expanding capacity of bone marrow-derived mesenchymal stem cells (MSCs) in 34 patients who received a marrow and/or peripheral blood stem cells transplant (SCT). Marrow samples were obtained from iliac crest aspirates of healthy individuals (normal controls) and patients for the isolation, purification, and expansion of MSCs. The different passage MSCs of patients were analyzed by flow cytometry (FCM) to reveal the cell surface antigen expression. The expanding function of MSCs from patients after SCT, which might be affected by cytotoxic therapy in the conditioning regimen, colony-forming unit-fibroblast (CFU-F), confluent time, and passage number of the culture were measured, and then compared with those in the normal controls. At the same time, the numbers of colony-forming unit of hematopoietic progenitor were detected and compared with normal controls. In addition, CFU-F, confluent time, and passage number of MSCs were compared between group of BMSCs plus PBSCs co-transplanted patients and group of BMSCs plus PBSCs with the second donor umbilical cord blood cells (UBCs) co-transplanted patients. The results indicated that a confluent monolayer of stroma cells was generated in 31 out of the 34 cases (91.1%), a subconfluent monolayer was generated in one case (2.9%), no adherent stromal layer was generated in 2 cases (5.9%). As compared with the normal controls, the time generating a confluent layer of stroma cells from primary MSCs of patients was longer significantly, and the passage number and CFU-F of MSCs of patients in vitro was less than that of normal controls significantly. Compared with the group of BMSCs plus PBSCs co-transplanted patients, the confluent time of MSCs in group of BMSCs plus PBMSCs with UBCs co-transplanted patients was shorter, the passage number and CFU-F count in this group were higher. It is concluded that the MSCs of patients after HSCT are damaged, and the co-transplant of BMSCs and PBSCs plus UBCs can partially improve in vitro expanding capacity of MSCs from patients.
Adolescent ; Adult ; Bone Marrow Cells ; pathology ; Cell Proliferation ; Cells, Cultured ; Female ; Fetal Blood ; cytology ; transplantation ; Hematologic Neoplasms ; pathology ; therapy ; Hematopoietic Stem Cell Transplantation ; Hematopoietic Stem Cells ; cytology ; Humans ; Male ; Mesenchymal Stromal Cells ; pathology ; Middle Aged ; Peripheral Blood Stem Cell Transplantation ; Young Adult

The aim of this study was to investigate the origin of bone marrow-derived mesenchymal cells in 34 patients who had received a sex-mismatched hematopoietic stem cells transplant (HSCT). The mesenchymal stem cells (MSC) from 34 patients were collected for test. The different passage MSC of patients were analyzed by flow cytometry (FCM) to reveal the cell surface antigen expression. The polymerase chain reaction (PCR) analysis of the amelogenin (AMEL) genes was used to detect donor cells from host cells. The cultured MSC were stained by fluorescence in situ hybridization (FISH) probes for chromosomes X (Xp11.1-Xq11.1) and Y (Yq12) to distinguish donor cells from host cells. The results indicated that 31 out of 34 cases showed the confluent stroma and 24 out of these 31 cases were successfully passaged for more than 5 generations which could be used for PCR and FISH analysis. According to FCM results the number of CD14+CD45+ cells, which was regarded as monocyte/macrophage from the cultured MSC (passage 5) was less than 0.04%. In PCR assay, the marrow-derived MSC from the passage 5 were found to be of host origin. FISH assay demonstrated that marrow-derived MSC from the passage 5 were found to be of host origin up to 100%. It is concluded that the origin of MSC in bone marrow of patients after allogeneic stem cell transplantation was confirmed to be derived still from the recipients their own.
Adolescent ; Adult ; Bone Marrow Cells ; pathology ; Cells, Cultured ; Chromosomes, Human, X ; genetics ; Chromosomes, Human, Y ; genetics ; Female ; Hematologic Neoplasms ; therapy ; Hematopoietic Stem Cell Transplantation ; Humans ; In Situ Hybridization, Fluorescence ; Leukocyte Common Antigens ; analysis ; Lipopolysaccharide Receptors ; analysis ; Male ; Mesenchymal Stromal Cells ; pathology ; Middle Aged ; Peripheral Blood Stem Cell Transplantation ; Transplantation Conditioning ; Transplantation, Homologous

This study was purposed to explore the caspase-independent apoptosis pathway in human multiple myeloma cell RPMI8226 induced by arsenic trioxide (As(2)O(3)). MTT method was used to analyze the proliferation inhibition rate; flow cytometry was used to detect the apoptosis rate; Western blot was used to determine the expressions of BCL-2 and Caspase-3 in RPMI8226 cells. The results showed that As(2)O(3) (0.1 - 20 µmol/L) significantly inhibited the proliferation of RPMI8226 (P < 0.05) in concentration- and time-dependent manner. Compared with the group treated with As(2)O(3) (10 µmol/L) alone, the apoptosis rate of zVAD-fmk (20 µmol/L) and As(2)O(3) combined treated group did not change. Compared with the group treated with As(2)O(3) (10 µmol/L) alone, zVAD-fmk (20 µmol/L) combined with As(2)O(3) (10 µmol/L) treatment group showed significant increase of expressions of Caspase-3 and BCL-2. It is concluded that As(2)O(3) can inhibit the proliferation of RPMI8226 cells. As(2)O(3) can induce apoptosis of RPMI8226 cells, and a caspase-independent process probably exist in As2O3-inducing RPMI8266 cells apoptosis.
Apoptosis ; drug effects ; Arsenicals ; pharmacology ; Caspase 3 ; metabolism ; Cell Line, Tumor ; Humans ; Multiple Myeloma ; metabolism ; pathology ; Oxides ; pharmacology ; Proto-Oncogene Proteins c-bcl-2 ; metabolism