Biomedical subjects

Bing Zhu

Publications and source records attributed to Bing Zhu.

At least 19 recordsLinked to original sources

PubMed2026

A 7-mm Covered TIPS Reduces Hepatic Encephalopathy Without Increasing Rebleeding in Cirrhotic Patients With Small Liver: A Randomized Study.

BACKGROUND/AIMS: International guidelines recommend initiating transjugular intrahepatic portosystemic shunt (TIPS) placement with an 8-mm stent. However, there is an evident lack of randomized controlled trials evaluating TIPS diameters < 8 mm in cirrhotic patients with a relatively small liver. The aim of this study was to determine whether 7 mm-covered TIPS, compared with 8-mm stents, could achieve comparable shunt function with a lower incidence of hepatic encephalopathy (HE). METHODS: In this multicenter randomized controlled trial, patients with cirrhosis and relatively small liver were randomized 1:1 to receive TIPS with a 7-mm (n = 92) or 8-mm (n = 92) covered stent to prevent variceal rebleeding. The primary endpoint was the incidence of overt HE after randomization. All-cause rebleeding, orthotopic liver transplantation (OLT)-free survival and a composite of these outcomes, were designated as secondary endpoints. RESULTS: Among the 184 enrolled patients, the predominant etiologies of liver cirrhosis were hepatitis B virus infection (56.0%) and alcohol-related liver disease (20.7%). Over a median follow-up of 26.5 months, overt HE occurred in 19 patients (20.7%) in the 7-mm group and 33 patients (35.9%) in the 8-mm group. The 2-year cumulative incidence of overt HE was significantly lower in the 7-mm group than in the 8-mm group (21.4% vs. 37.2%, p = 0.02). Stent diameter, post-TIPS portosystemic pressure gradient, pre-covert HE and MELD-Na score were identified as independent risk factors for overt HE. The rates of shunt dysfunction were statistically similar between groups (8.7% vs. 8.7%, p = 1.0), as were 2-year rebleeding rates (10.9% vs. 9.8%, p = 0.81) and OLT-free survival rates (91.3% vs. 88.0%, p = 0.82). CONCLUSIONS: A 7-mm covered TIPS demonstrated comparable shunt function to an 8-mm covered stents, with a significantly lower risk of overt HE. These findings support consideration of 7-mm TIPS stents for preventing variceal rebleeding in cirrhotic patients with a small liver who are undergoing TIPS. TRAIL REGISTRATION: ClinicalTrials.gov, NCT02541825.

Humans↗

PubMed2007

Metabolism and excretion of the dipeptidyl peptidase 4 inhibitor [14C]sitagliptin in humans.

The metabolism and excretion of [(14)C]sitagliptin, an orally active, potent and selective dipeptidyl peptidase 4 inhibitor, were investigated in humans after a single oral dose of 83 mg/193 muCi. Urine, feces, and plasma were collected at regular intervals for up to 7 days. The primary route of excretion of radioactivity was via the kidneys, with a mean value of 87% of the administered dose recovered in urine. Mean fecal excretion was 13% of the administered dose. Parent drug was the major radioactive component in plasma, urine, and feces, with only 16% of the dose excreted as metabolites (13% in urine and 3% in feces), indicating that sitagliptin was eliminated primarily by renal excretion. Approximately 74% of plasma AUC of total radioactivity was accounted for by parent drug. Six metabolites were detected at trace levels, each representing <1 to 7% of the radioactivity in plasma. These metabolites were the N-sulfate and N-carbamoyl glucuronic acid conjugates of parent drug, a mixture of hydroxylated derivatives, an ether glucuronide of a hydroxylated metabolite, and two metabolites formed by oxidative desaturation of the piperazine ring followed by cyclization. These metabolites were detected also in urine, at low levels. Metabolite profiles in feces were similar to those in urine and plasma, except that the glucuronides were not detected in feces. CYP3A4 was the major cytochrome P450 isozyme responsible for the limited oxidative metabolism of sitagliptin, with some minor contribution from CYP2C8.

Adenosine Deaminase↗

PubMed2006

Effective regularity in modulation on gastric motility induced by different acupoint stimulation.

AIM: To investigate whether manual acupuncture at representative acupoints in different parts of the body can modulate responses of gastric motility in rats and regular effects in different acupoint stimulation. METHODS: The gastric motor activity of rats was recorded by the intrapyloric balloon. The changes of gastric motility induced by the stimulation were compared with the background activity in intragastric pressure and/or waves of gastric contraction recorded before any stimulation. Morphological study was also conducted by observing the Evans dye extravasation in the skin after mustard oil injection into the intragastric mucous membrane to certify cutaneous innervations of blue dots related to gastric segmental innervations. RESULTS: In all six rats that received mustard oil injections into intragastric mucosa, small blue dots appeared in the skin over the whole abdomen, but mainly in peri-midline upper- and middle- abdomen and middle-back, a few in thigh and groin. It may speculate that cutaneous innervations of blue dots have the same distribution as gastric segmental innervations. Acu-stimulation in acupoints of head-neck, four limbs, upper chest-dorsum and lower-dorsum induced markedly augmentation of gastric motility (acupoints on head-neck such as St-2: n = 16, 105.19 +/- 1.36 vs 112.25 +/- 2.02 and St-3: n = 14, 101.5 +/- 1.75 vs 109.36 +/- 1.8; acupoints on limbs such as Sp-6: n = 19, 100.74 +/- 1.54 vs 110.26 +/- 3.88; St-32: n = 17, 103.59 +/- 1.64 vs 108.24 +/- 2.41; St-36: n = 16, 104.81 +/- 1.72 vs 110.81 +/- 2.74 and Li-11: n = 17, 106.47 +/- 2.61 vs 114.77 +/- 3.77, P < 0.05-0.001). Vigorous inhibitory regulations of gastric motility induced by acu-stimulation applied in acupoints on whole abdomen and middle-dorsum were significantly different as compared with the controls before acu-stimulation (abdomen acupoints such as Cv-12: n = 11, 109.36 +/- 2.09 vs 101 +/- 2.21; Cv-6: n = 18, 104.39 +/- 1.42 vs 91.83 +/- 3.22 and St-21: n = 12, 107 +/- 2.97 vs 98.58 +/- 2.81; acupoints on middle-dorsum such as Bl-17: n = 19, 100.63 +/- 1.4 vs 92.21 +/- 2.07 and Bl-21: n = 19, 103.84 +/- 1.48 vs 97.58 +/- 2.16, P < 0.05-0.001). CONCLUSION: Regular regulatory effects of facilitation and inhibition on gastric motility appear to be somatotopically organized in the acupoints of whole body, and the effective regularity of site-special acupoints on gastric motility is involved in segmental innervations between stomach and acupoints.

Acupuncture↗

PubMed2006

Chemoprevention of bicyclol against hepatic preneoplastic lesions.

Oral administration of 100 and 200 mg/kg body weight/day of 4,4-dimethoxy-5,6,5', 6'-dimethylene-dioxy-2-hydroxymethyl-2'-carbonyl biphenyl, Bicyclol, inhibited rat hepatic preneoplastic lesions induced by diethylnitrosamine (DEN). Bicyclol reduced densities of number and area of gamma-glutamyltransferase positive foci, indexes for neoplastic hyperplasia; and also suppressed protein expressions for glutathione S transferase P isoform (GST-P) and alpha-fetal protein and mRNA for N-ras, c-myc and PKCalpha genes. With increases of total microsomal P450 and specific CYP2B1 activities in normal rat liver, Bicyclol enhanced particularly the denitrosation of DEN, a low toxic pathway of metabolism. There is a minor effect of Bicyclol on the deethylation of DEN to produce highly mutagenic metabolites. These results suggest that Bicyclol exists the ability of protecting hepatocytes from the mutagenicity of DEN. Such hypothesis was validated by the observation that Bicyclol inhibited DEN-induced unscheduled DNA synthesis, a DNA damage index, in primary cultured rat hepatocytes. More, in virto Bicyclol inhibited two-stages transformation of mice fibroblastic Balb/c 3T3 cells induced by 3-methylcholanthrene and tetradecanoyl-phorbol 13-acetate (TPA), and blocked the anchorage-independent growth of transformed cells in soft agar. Bicyclol also suppressed TPA-stimulated Balb/c 3T3 cell proliferation in both cell number and 3H-thymidine incorporation. Dot blot indicated that Bicyclol inhibited mRNA expressions of H-ras, c-myc and PKCalpha genes by TPA-stimulation. These data demonstrate that Bicyclol prevents carcinogens-induced animal neoplasm and cell malignant transformation via mechanisms at stages of initiation and promotion. It substantiates those evidences that Bicyclol would be used as potential a chemopreventive agent for hepatocarcinogenesis along with its major therapy against chronic anti-hepatitis.

Animals↗

PubMed2006

Role of neuronal nitric oxide synthase and inducible nitric oxide synthase in intestinal injury in neonatal rats.

AIM: To investigate the dynamic change and role of neuronal nitric oxide synthase (nNOS) and inducible nitric oxide synthase (iNOS) in neonatal rat with intestinal injury and to define whether necrotizing enterocolitis (NEC) is associated with the levels of nitric oxide synthase (NOS) in the mucosa of the affected intestine tissue. METHODS: Wistar rats less than 24 h in age received an intraperitoneal injection with 5 mg/kg lipopolysaccharide (LPS). Ileum tissues were collected at 1, 3, 6, 12 and 24 h following LPS challenge for histological evaluation of NEC and for measurements of nNOS and iNOS. The correlation between the degree of intestinal injury and levels of NOS was determined. RESULTS: The LPS-injected pups showed a significant increase in injury scores versus the control. The expression of nNOS protein and mRNA was diminished after LPS injection. There was a negative significant correlation between the nNOS protein and the grade of median intestinal injury within 24 h. The expression of iNOS protein and mRNA was significantly increased in the peak of intestinal injury. CONCLUSION: nNOS and iNOS play different roles in LPS-induced intestinal injury. Caution should be exerted concerning potential therapeutic uses of NOS inhibitors in NEC.

Animals↗

PubMed2006

(2S,3S)-3-Amino-4-(3,3-difluoropyrrolidin-1-yl)-N,N-dimethyl-4-oxo-2-(4-[1,2,4]triazolo[1,5-a]-pyridin-6-ylphenyl)butanamide: a selective alpha-amino amide dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes.

A series of beta-substituted biarylphenylalanine amides were synthesized and evaluated as inhibitors of dipeptidyl peptidase IV (DPP-4) for the treatment of type 2 diabetes. Optimization of the metabolic profile of early analogues led to the discovery of (2S,3S)-3-amino-4-(3,3-difluoropyrrolidin-1-yl)-N,N-dimethyl-4-oxo-2-(4-[1,2,4]triazolo[1,5-a]pyridin-6-ylphenyl)butanamide (6), a potent, orally active DPP-4 inhibitor (IC(50) = 6.3 nM) with excellent selectivity, oral bioavailability in preclinical species, and in vivo efficacy in animal models. Compound 6 was selected for further characterization as a potential new treatment for type 2 diabetes.

Administration, Oral↗

PubMed2006

Histone H2B monoubiquitination functions cooperatively with FACT to regulate elongation by RNA polymerase II.

Over the past years, a large number of histone posttranslational modifications have been described, some of which function to attain a repressed chromatin structure, while others facilitate activation by allowing access of regulators to DNA. Histone H2B monoubiquitination is a mark associated with transcriptional activity. Using a highly reconstituted chromatin-transcription system incorporating the inducible RARbeta2 promoter, we find that the establishment of H2B monoubiquitination by RNF20/40 and UbcH6 is dependent on the transcription elongation regulator complex PAF, the histone chaperone FACT, and transcription. H2B monoubiquitination facilitates FACT function, thereby stimulating transcript elongation and the generation of longer transcripts. These in vitro analyses and corroborating in vivo experiments demonstrate that elongation by RNA polymerase II through the nucleosomal barrier is minimally dependent upon (1) FACT and (2) the recruitment of PAF and the H2B monoubiquitination machinery.

Animals↗

PubMed2006

Chemosensitizing multiple drug resistance of human carcinoma by Bicyclol involves attenuated p-glycoprotein, GST-P and Bcl-2.

Bicyclol, a second generation of synthetic hepatoprotectant being used in China for anti-hepatitis therapy, shows chemosensitizing effect on reverting multiple drug resistance (MDR) of cytostatic agents in two established MDR carcinoma cell lines, vincristine resistant human stomatic epidermoid carcinoma VinRKB and adriamycin resistant human breast carcinoma AdrRMCF-7. The reversal rate of drug resistance was calculated from the changes of the IC50 of cell growth inhibition. Bicyclol at the concentration of 25, 50, 100 microM induced 2.8 7.3 and 20.7 fold, respectively, reversal of vincristine resistance in VinRKB cell. Bicyclol also reversed the cross-resistance of VinRKB cell to taxol and AdrRMCF-7 cell resistance to adriamycin at the similar range of potency. Further, Bicyclol recovered the reduced accumulation of adriamycin in AdrRMCF-7 cell partially to the level in drug-sensitive MCF-7 cell, indicate the inhibition of MDR related membrane efflux pump system. Overexpression of membrane p-glycoprotein coded by Mdr-1 genes, the most common efflux pump correlated to MDR, was found in both VinRKB and AdrRMCF-7 cells by Western blot and immunocytochemistry as compared with drug-sensitive cells. The p-glycoprotein was decreased to the levels in drug-sensitive cells when VinRKB and AdrRMCF-7 cells were treated with Bicyclol for 12-72 hours. Both VinRKB and AdrRMCF-7 cells showed increased GSH contents, and AdrRMCF-7 cell showed increased GST activity and the overexpression of Bcl-2 protein, by which molecules are tightly related to the MDR formation besides Mdr-1 p-glycoprotein. Bicyclol reduced the GSH contents, GST activities and Bcl-2 expression. All these data demonstrate that, by modifying the expressions of Mdr-1, GSH/GST and Bcl-2, Bicyclol increases the intracellular drug concentration and sensitizes the resistant cells to the anti-carcinoma agents.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2006

Differential role of programmed death-ligand 1 [corrected] and programmed death-ligand 2 [corrected] in regulating the susceptibility and chronic progression of experimental autoimmune encephalomyelitis.

Programmed death-1 (PD-1) is a negative costimulatory molecule, and blocking the interaction of PD-1 with its ligands, PD-L1 (B7-H1) and PD-L2 (B7-DC), enhances autoimmune disease in several animal models. We have studied the role of PD-1 ligands in disease susceptibility and chronic progression in experimental autoimmune encephalomyelitis (EAE). In BALB/c mice immunized with myelin oligodendrocyte glycoprotein (MOG) peptide 35-55, PD-L1 but not PD-L2 blockade significantly increased EAE incidence. In B10.S mice immunized with myelin proteolipid protein (PLP) peptide 139-151, both PD-L1 and PD-L2 blockade markedly enhanced EAE severity. In prediabetic NOD mice immunized with PLP48-70, PD-L2 blockade worsened EAE but did not induce diabetes, whereas PD-L1 blockade precipitated diabetes but did not worsen EAE, suggesting different regulatory roles of these two ligands in EAE and diabetes. B6 mice immunized with MOG35-55 developed chronic persistent EAE, and PD-L2 blockade in the chronic phase exacerbated EAE, whereas PD-L1 blockade did not. In contrast, SJL/J mice immunized with PLP139-151 developed chronic relapsing-remitting EAE, and only PD-L1 blockade during remission precipitated EAE relapse. The strain-specific effects of PD-1 ligand blockade did not correlate with the expression of PD-L1 and PD-L2 on dendritic cells and macrophages in lymphoid tissue, or on inflammatory cells in the CNS. However, EAE enhancement is correlated with less prominent Th2 cytokine induction after specific PD-1 ligand blockade. In conclusion, PD-L1 and PD-L2 differentially regulate the susceptibility and chronic progression of EAE in a strain-specific manner.

Animals↗

PubMed2006

8-chloroadenosine induced HL-60 cell growth inhibition, differentiation, and G(0)/G(1) arrest involves attenuated cyclin D1 and telomerase and up-regulated p21(WAF1/CIP1).

8-Chloroadenosine, an active dephosphorylated metabolite of the antineoplastic agent 8-chloroadenosine 3',5'-monophosphate (8-Cl-cAMP), induces growth inhibition in multiple carcinomas. Here we report that 8-chloroadenosine inhibits growth in human promyelocytic leukemia HL-60 cells by a G(0)/G(1) phase arrest and terminates cell differentiation along the granulocytic lineage. The mechanism of 8-chloroadenosine-induced G(0)/G(1) arrest is independent of apoptosis. The expressions of cyclin D1 and c-myc in HL-60 are suppressed by 8-chloroadenosine, whereas the cyclin-dependent kinases inhibitor p21(WAF1/CIP1) is up-regulated. 8-Chloroadenosine has less effect on the expressions of cyclin-dependent kinase (cdk)2 and cdk4, G(1) phase cyclin-dependent kinases, and only moderately induces the expression of transforming growth factor beta1 (TGFbeta1) and the mitotic inhibitor p27(KIP1). Telomerase activity is reduced in extracts of 8-chloroadenosine treated HL-60 cells, but 8-chloroadenosine does not directly inhibit the catalytic activity of telomerase in vitro. Therefore, anti-proliferation of HL-60 cells by 8-chloroadenosine involves coordination of cyclin D1 suppression, reduction of telomerase activity, and up-regulation of p21(WAF1/CIP1) that arrest cell-cycle progression at G(0)/G(1) phase and terminate cell differentiation.

2-Chloroadenosine↗

PubMed2006

Comparative genomic analysis of two strains of human adenovirus type 3 isolated from children with acute respiratory infection in southern China.

Human adenovirus type 3 (HAdV-3) is a causative agent of acute respiratory disease, which is prevalent throughout the world, especially in Asia. Here, the complete genome sequences of two field strains of HAdV-3 (strains GZ1 and GZ2) isolated from children with acute respiratory infection in southern China are reported (GenBank accession nos DQ099432 and DQ105654, respectively). The genomes were 35,273 bp (GZ1) and 35,269 bp (GZ2) and both had a G+C content of 51 mol%. They shared 99% nucleotide identity and the four early and five late regions that are characteristic of human adenoviruses. Thirty-nine protein- and two RNA-coding sequences were identified in the genome sequences of both strains. Protein pX had a predicted molecular mass of 8.3 kDa in strain GZ1; this was lower (7.6 kDa) in strain GZ2. Both strains contained 10 short inverted repeats, in addition to their inverted terminal repeats (111 bp). Comparative whole-genome analysis revealed 93 mismatches and four insertions/deletions between the two strains. Strain GZ1 infection produced a typical cytopathic effect, whereas strain GZ2 did not; non-synonymous substitutions in proteins of GZ2 may be responsible for this difference.

Acute Disease↗

PubMed2006

Drosophila Paf1 modulates chromatin structure at actively transcribed genes.

The Paf1 complex in yeast has been reported to influence a multitude of steps in gene expression through interactions with RNA polymerase II (Pol II) and chromatin-modifying complexes; however, it is unclear which of these many activities are primary functions of Paf1 and are conserved in metazoans. We have identified and characterized the Drosophila homologs of three subunits of the yeast Paf1 complex and found striking differences between the yeast and Drosophila Paf1 complexes. We demonstrate that although Drosophila Paf1, Rtf1, and Cdc73 colocalize broadly with actively transcribing, phosphorylated Pol II, and all are recruited to activated heat shock genes with similar kinetics; Rtf1 does not appear to be a stable part of the Drosophila Paf1 complex. RNA interference (RNAi)-mediated depletion of Paf1 or Rtf1 leads to defects in induction of Hsp70 RNA, but tandem RNAi-chromatin immunoprecipitation assays show that loss of neither Paf1 nor Rtf1 alters the density or distribution of phosphorylated Pol II on the active Hsp70 gene. However, depletion of Paf1 reduces trimethylation of histone H3 at lysine 4 in the Hsp70 promoter region and significantly decreases the recruitment of chromatin-associated factors Spt6 and FACT, suggesting that Paf1 may manifest its effects on transcription through modulating chromatin structure.

Animals↗

PubMed2006

[Case analysis on treatment and recurrence of giant cell tumor of bone].

OBJECTIVE: To analyze the clinical features, treatment methods, and recurrence factors of giant cell tumor of the bone and to investigate the surgical therapy choice for the tumor around the knees. METHODS: Thirty-eight patients (13 males and 25 females; average age 31.1 years, range 14-59 years) with giant cell tumor of the bone were treated and followed up from January 1993 to January 2005. The patients' diagnoses were established by biopsies of the specimens from the preoperative punctures or operations. The clinical features and the radiological and laboratory data from the 38 patients were reviewed. By the Campanacci's radiological grading system, 5 patients were in Grade I, 22 in Grade II, and 11 in Grade III . By the Enneking classification, 9 patients were in Grade I, 21 in Grade II, and 8 in Grade III . By the Jaffe's classification, 7 patients were in Grade I, 24 in Grade II, and 7 in Grade III. The intralesional excision (curettage) with the bone grafting was performed on 4 patients; the curettage with some adjuvant treatments (high-speed burring, phenol, alcohol, cement, hydrogen peroxide, 50% ZnCl2, 3% iodine tincture, or bone cement) was used in 26 patients; and resection of the whole tumor was performed on 8 patients. RESULTS: The follow-up of the 38 patients for 12-144 months (average, 67 months) revealed that giant cell tumor of the bone was found around the knees in 29 of the 38 patients (13 at the distal femur, 16 at the proximal tibia), at the proximal femur in 2, at the proximal ulna in 2, at the distal radius in 2, at the sacroiliac area in 2, and at lumbar spine in 1. Of the 38 patients, 4 had a recurrence after simple curettage, 8 had no recurrence after resection of the whole tumor, and 8 of the remaining 26 patients had a recurrence after curettage with some adjuvant treatments. Five patients in Grade I (Campanacci's radiological grading) had no recurrence, 6 of the 11 patients in Grade II had a recurrence, and 6 of the 11 patients in Grade III had a recurrence. Two of the 9 patients in Grade I (Enneking grading) had a recurrence, 6 of the 21 patients in Grade II had a recurrence, and 4 of the patients in Grade III had a recurrence; all the recurrent lesions were around the knee, with a duration of the recurrence ranging from 2 months to 36 months (average, 14.3 months). Of the patients with the recurrence, 12 underwent reoperations (8 by the total resection of the recurrent tumor, 4 by the curettage with adjuvant treatments), and there was no recurrence after the reoperation. CONCLUSION: Giant cell tumor of the bone usually recurs around the knee joint, especially at the proximal tibia, usually graded as Grade II or III by the Campanacci's radiological grading system. Simple curettage has a higher recurrence rate; therefore, extensive curettage and resection of the lesions combined with some adjuvant treatments after the correct diagnosis can be used to reduce the high recurrence rate of giant cell tumor of the bone.

Adolescent↗

PubMed2005

Monoubiquitination of human histone H2B: the factors involved and their roles in HOX gene regulation.

In yeast, histone H2B monoubiquitination is a cotranscriptional event regulating histone H3 methylation at lysines 4 and 79. However, mammalian H2B monoubiquitination remains poorly understood. We report that in humans, the 600 kDa RNF20/40 complex is the E3 ligase and UbcH6 is the ubiquitin E2-conjugating enzyme for H2B-Lys120 monoubiquitination. RNF20 and RNF40 are both homologs of Bre1, the E3 ligase in the yeast case. UbcH6 physically interacts with RNF20/40 and with the hPAF complex. Formation of a trimeric complex with hPAF stimulates H2B monoubiquitination activity in vitro. Accordingly, UbcH6, RNF20/40, and the hPAF complex are recruited to transcriptionally active genes in vivo. RNF20 overexpression leads to elevated H2B monoubiquitination, subsequently higher levels of methylation at H3 lysines 4 and 79, and stimulation of HOX gene expression. In contrast, RNAi against the RNF20/40 complex or hPAF complex reduces H2B monoubiquitination, lowers methylation levels at H3 lysines 4 and 79, and represses HOX gene expression.

DNA Methylation↗

PubMed2005

Faraday-Michelson system for quantum cryptography.

Quantum key distribution provides unconditional security for communication. Unfortunately, current experimental schemes are not suitable for long-distance fiber transmission because of phase drift or Rayleigh backscattering. In this Letter we present a unidirectional intrinsically stable scheme that is based on Michelson-Faraday interferometers, in which ordinary mirrors are replaced with 90 degree Faraday mirrors. With the scheme, a demonstration setup was built and excellent stability of interference fringe visibility was achieved over a fiber length of 175 km. Through a 125 km long commercial communication fiber cable between Beijing and Tianjin, the key exchange was performed with a quantum bit-error rate of less than 6%, which is to our knowledge the longest reported quantum key distribution experiment under field conditions.

Journal Article↗

PubMed2005

[Therapeutic effects of recombinant mutant human tumor necrosis factor-related apoptosis-inducing ligand on non-small lung cell cancer: an experimental with rats].

OBJECTIVE: To evaluate the therapeutic effects of recombinant mutant human tumor necrosis factor-related apoptosis-inducing ligand (rmhTRAIL) on non-small cell cancer (NSCLC). METHODS: NSCLC cells of the line NCI-H460 were cultured and underwent agarose gel electrophoresis. rmhTRAIL of different concentrations was added into the culture fluid to observe the influence of rmhTRAIL. Nude BALB/c rats were transplanted with rat NCI-H460 tumor. Then the rats carrying xenografts were randomly divided into 5 groups of 8 rats: negative control group to be injected intraperitoneally with normal saline; positive control group to be injected with vancristine; low-dose rmhTRAIL group, to be injected with 1.7 mg/kg rmhTRAIL, middle-dose rmhTRAIL group to be injected with rmhTRAIL 5.0 mg/kg, and high-dose rmhTRAIL group to be injected with 15.0 mg/kg rmhTRAIL. The size of tumor was measured every 3 approximately 4 days. Ten days after the administration of different drugs the rats were killed and the tumors were taken out to undergo TUNEL staining for microscopy. RESULTS: The relative tumor volume of the low-dose rmhTRAIL group and high-dose rmhTRAIL group were 3.19 +/- 2.05 and 1.47 +/- 0.77 respectively, both significantly smaller than that of the negative group (8.48 +/- 5.87, P < 0.05 and P < 0.01). The relative tumor growth rate of the low-dose rmhTRAIL group and high-dose rmhTRAIL group were 37.6% and 17.3% respectively. The tumor weight of low-dose rmhTRAIL group and high-dose rmhTRAIL group were 1.09 g +/- 0.55 g and 0.31 g +/- 0.09 g respectively, both significantly lighter than that of the negative control group (2.78 +/- 0.77, both P < 0.01). Large amount of apoptotic cells were seen in the tumor tissues of the rmhTRAIL -treated rats and tumors cells cultured with rmhTRAIL. Agarose gel electrophoresis showed apoptosis-characteristic ladder in the DNA extracted from the rmhTRAIL -treated tumors cells. CONCLUSION: rmhTRAIL dose-dependently inhibit the growth of NSCLC cells, primarily by inducing apoptosis of tumor cells.

Animals↗

PubMed2005

The human PAF complex coordinates transcription with events downstream of RNA synthesis.

The yeast PAF (yPAF) complex interacts with RNA polymerase II and coordinates the setting of histone marks associated with active transcription. We report the isolation and functional characterization of the human PAF (hPAF) complex. hPAF shares four subunits with yPAF (hCtr9, hPaf1, hLeo1, and hCdc73), but contains a novel higher eukaryotic-specific subunit, hSki8. RNAi against hSki8 or hCtr9 reduces the cellular levels of other hPAF subunits and of mono- and trimethylated H3-Lys 4 and dimethylated H3-Lys 79. The hSki8 subunit is also a component of the human SKI (hSKI) complex. Yeast SKI complex is cytoplasmic and together with Exosome mediates 3'-5' mRNA degradation. However, hSKI complex localizes to both nucleus and cytoplasm. Immunoprecipitation experiments revealed that hPAF and hSKI complexes interact, and ChIP experiments demonstrated that hSKI associates with transcriptionally active genes dependent on the presence of hPAF. Thus, in addition to coordinating events during transcription (initiation, promoter clearance, and elongation), hPAF also coordinates events in RNA quality control.

HeLa Cells↗

PubMed2005

Effects of augmentation of liver regeneration recombinant plasmid on rat hepatic fibrosis.

AIM: To investigate the effects of eukaryotic expression of plasmid on augmentation of liver regeneration (ALR) in rat hepatic fibrosis and to explore their mechanisms. METHODS: Ten rats were randomly selected from 50 Wistar rats as normal control group. The rest were administered intraperitoneally with porcine serum twice weekly. After 8 wk, they were randomly divided into: model control group, colchicine group (Col), first ALR group (ALR1), second ALR group (ALR2). Then colchicine ALR recombinant plasmid were used to treat them respectively. At the end of the 4th wk, rats were killed. Serum indicators were detected and histopathological changes were graded. Expression of type I, III, collagen and TIMP-1 were detected by immunohistochemistry and expression of TIMP-1 mRNA was detected by semi-quantified RT-PCR. RESULTS: The histologic examination showed that the degree of the rat hepatic fibrosis in two ALR groups was lower than those in model control group. Compared with model group, ALR significantly reduced the serum levels of ALT, AST, HA, LN, PCIII and IV (P<0.05). Immunohistochemical staining showed that expression of type I, III, collagen and TIMP-1 in two ALR groups was ameliorated dramatically compared with model group (I collagen: 6.94+/-1.42, 5.80+/-1.66 and 10.83+/-3.58 in ALR1, ALR2 and model groups, respectively; III collagen: 7.18+/-1.95, 4.50+/-1.67 and 10.25+/-2.61, respectively; TIMP-1: 0.39+/-0.05, 0.20+/-0.06 and 0.53+/-0.12, respectively, P<0.05 or P<0.01). The expression level of TIMP-1 mRNA in the liver tissues was markedly decreased in two ALR groups compared with model group (TIMP-1 mRNA/beta-actin: 0.89+/-0.08, 0.65+/-0.11 and 1.36+/-0.11 in ALR1, ALR2 and model groups respectively, P<0.01). CONCLUSION: ALR recombinant plasmid has beneficial effects on rat hepatic fibrosis by enhancing regeneration of injured liver cells and inhibiting TIMP-1 expressions.

Animals↗