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Biomedical subjects

Jun Lin

Publications and source records attributed to Jun Lin.

At least 55 records · Page 3Linked to original sources

Novel polynuclear platinum adducts detected during the reactions of [Pt(Met-S,N)Cl2] with gamma-glutathione and L-cysteine.

The reactions of platinum(II) complexes with thiol containing molecules are highly relevant to the mechanism of action of platinum-based drugs. This work presents the electrospray mass spectrometry (ESMS) and NMR results on the reactions of [Pt(l-MetH-S,N)Cl(2)] (l-MetH: l-methionine) with gamma-glutathione (GSH) and l-cysteine (l-Cys) at different pH and different molar ratios. Polymeric species such as [Pt(2)(micro-SG-S)(2)(Met-S,N)(2)], [Pt(3)(micro-SG-S)(4)(Met-S,N)(2)], [Pt(4)(micro-SG-S)(6)(Met-S,N)(2)] and [Pt(5)(micro-SG-S)(8)(Met-S,N)(2)] (l-Met: deprotonated l-methionine) were detected and were stable for long hours. For both reactions, the polymerization extent decreased with the increase of pH. For the reaction of l-Cys, only mononuclear complex [Pt(l-Met-S,N)(l-Cys-S,N)] was observed when pH>9. The observation and identification of polymeric (higher than binuclear) adducts of Pt(II)/GSH and Pt(II)/l-Cys appears to be unprecedented.

Cisplatin↗

Effect of two human growth hormone receptor antagonists on glomerulosclerosis in streptozotocin-induced diabetic rats.

AIM: To explore the feasibility of human growth hormone (hGH) receptor antagonist in the treatment of end-stage diabetic renal complications. METHODS: Two hGH mutants, hGHA1 (Cys-hGH-del1-4, G120R, K168A, E174A, C182S, del186-191) and hGHA2 (hGH-H21A, G120R, E174A) were expressed in E coli. The IC50 (Mean+/-SD) values for the mutants for inhibiting 125I-hGH binding to rabbit growth hormone receptor were (65+/-10) ng for hGHA1, (27+/-5.6) ng for hGHA2, and (10+/-0.6) ng for wild type hGH, respectively. RESULTS: After treatment for 12 weeks, the renal histology analysis showed that treatment with hGHA2 at 4 mg/kg body weight daily markedly suppressed glomerulosclerosis in streptozotocin-induced diabetic Sprague-Dawley (SD) rats; hGHA1 at the same dosage slightly increased the renal damage compared with saline; while wild type hGH at 1 U/kg body weight daily severely worsened the glomerulo-sclerosis in diabetic SD rats. CONCLUSION: The data indicated that hGHA2 inhibited the end-stage glomerulosclerosis in diabetic rats, but hGHA1 mildly increased the glomerulosclerosis.

Animals↗

Toward the design of novel polynuclear platinum antitumor complexes: a polydentate ligand system based on dipyridylamine and 1,3,5-trimethylenebenzene.

A novel hexadentate ligand, N,N,N',N',N",N"-hexa(2-pyridyl)-1,3,5-tris(aminomethyl)benzene (L), was designed and synthesized. The X-ray structure analysis reveals that the three dipyridylamine (DPA) groups of L are almost perpendicular to the central trimethylenebenzene, and two of them are spacially close to each other while the third one is further apart. The trinuclear Pt(II) complexes [Pt(3)LCl(6)] (1) and [Pt(3)L(CBDCA)(3)] (2) (where CBDCA represents cyclobutane dicarboxylic acid) were prepared and fully characterized by IR, NMR, and ESMS spectroscopy. A mononuclear complex, [PtL(CBDCA)] (3), was also prepared and structurally characterized, which suggests that controlled formation of mono-, di-, and trinuclear complexes with L is possible. Spectroscopic data showed that complexes 2 and 3 are able to bind to calf thymus DNA and their CBDCA group can be readily replaced by thiourea.

2,2'-Dipyridyl↗

Monofunctional platinum complexes showing potent cytotoxicity against human liver carcinoma cell line BEL-7402.

Three novel Pt(II) complexes [PtL(1)'Cl] I (L(1)' = glycine-N'-8-quinolylamide), [PtL(2)'Cl] II (L(2)' = l-alanine-N'-8-quinolylamide), and [PtL(3)Cl] III [L(3) = N-(tert-butoxycarbonyl)-l-methionine-N'-8-quinolylamide] have been synthesized and characterized. The crystal structure of complexes II and III showed that the ligands are three-coordinated with only one Cl(-) as the leaving group. Complex II crystallized in the monoclinic system with space group P2(1), a = 9.502(2) A, b = 4.724(1) A, c = 14.800(3) A, while complex III crystallized in the orthorhombic system with space group P2(1)2(1)2(1), a = 5.441(1) A, b = 12.978(3) A, c = 29.438(6) A. These complexes have been tested against a wide range of tumor cell lines including BEL-7402, HCT-116, SPC-A4, MOLT-4, P388, HL-60, A-549, SGC-7901, MKN-28, and HO-8910. Complex III is highly cytotoxic against the HCT-116 (IC(50) = 0.38 microM), SPC-A4 (IC(50) = 0.43 microM), BEL-7402 (IC(50) = 0.43 microM), and MOLT-4 (IC(50) = 0.61 microM) cell lines. The cell line most sensitive to III is human liver carcinoma cell line BEL-7402, which has a response rate of 75.1% at 6.6 x 10(-7) M, nearly 6 times higher than that of cisplatin.

Antineoplastic Agents↗

Photocatalytic activity, antibacterial effect, and photoinduced hydrophilicity of TiO2 films coated on a stainless steel substrate.

Transparent TiO2 films on stainless steel prepared by dip coating in a nonionic microemulsions solution have been shown to have much higher photocatalytic activity than those coatings on glass. Fe3+ and Fe2+ ions, diffusing from stainless steel substrate into TiO2 films during high-temperature calcination, behave as dopants to significantly affect the films' photocatalytic activity. An optimum calcination condition, under which the amount of diffused Fe3+ and the ratio of Fe3+ to Fe2+ ions favor the film's photocatalytic reaction, was obtained. In addition, this TiO2 films also exhibits excellent photoinduced hydrophilicity and antibacterial effect for the sterilization of Bacillus pumilus. As stainless steel is a very common material, practical systems for pollution treatment and disinfection may be designed based on this enhanced coating.

Acetone↗

Direct sonochemical preparation of high-surface-area nanoporous ceria and ceria-zirconia solid solutions.

For the first time, nanoporous ceria and ceria-zirconia solid solutions with high surface area have been successfully synthesized directly via high-intensity ultrasound irradiation without thermal post-treatment. The ceria and the solid solutions were characterized by XRD, TEM, and nitrogen adsorption. It was found that the nanoporous structures of the materials obtained were formed by the agglomeration of monodispersed nanoparticles under high-intensity ultrasound irradiation.

Journal Article↗

5-Fluorouracil-cisplatin adducts with potential antitumor activity.

Using 5-fluorouracil (5-FU) and cis-diamminedichloroplatinum(II) (cisplatin, CDDP) as starting compounds, 5-FU-cisplatin adducts cis-[Pt(NH(3))(2)(HFU)Cl] (1) and cis-[Pt(NH(3))(2)(HFU)(2)] (2) were prepared. The obtained complexes were characterized by IR, ES-MS and 1H NMR spectroscopy. Complex 1 reacted with guanosine-5'-monophosphate (5'-GMP) and gave rise to a stable mixed-ligand complex cis-[Pt(NH(3))(2)(HFU)(GMP)] (3), whereas 2 did not undergo a similar reaction. In vitro cell growth inhibition tests of complexes 1 and 2 exhibited moderate antitumor activities against the melanoma B16-BL6 cell line. This work provides the basis for a potential alternative for the combinational use of 5-FU and CDDP in cancer therapy.

Animals↗

Novel Cu(II)-quinoline carboxamide complexes: structural characterization, cytotoxicity and reactivity towards 5'-GMP.

Three new ligands, N-(8-quinolyl)pyridine-2-carboxamide (HL1), N-(8-quinolyl)glycine-N'-Boc-carboxamide (HL2), N-(8-quinolyl)-L-alanine-N'-Boc-carboxamide (HL3), and their Cu(II) complexes have been synthesized. Crystallographic data reveal that complex I, [Cu(L1)(Ac)(H2O)], is penta-coordinated with a square-pyramidal geometry while complexes V [Cu(L2')(H2O)] and VI [Cu(L3')(H2O)] are tetra-coordinated to give square planar geometry. In vitro tests showed that the Cu(II) complexes with L1 (I-IV) exhibited cytotoxicity at a concentration of 10(-8) M against murine leukemia P-388 and human leukemia HL-60 cell lines, which is more potent than cisplatin. However, ligands HL2 and HL3 and their corresponding copper complexes demonstrated very weak in vitro activities towards the cell lines examined. ESMS data shows that complex I binds rapidly with 5'-GMP to form 1:1 and 2:2 adduct.

Alanine↗

Fluoroquinolone-resistant Campylobacter in animal reservoirs: dynamics of development, resistance mechanisms and ecological fitness.

Thermophilic Campylobacter species, including Campylobacter jejuni and Campylobacter coli, are responsible for foodborne campylobacteriosis in humans and are increasingly resistant to fluoroquinolone (FQ) antimicrobials. The therapeutic use of FQ antimicrobial agents in food animal production, particularly in poultry, has become a concern for public health, because the practice may promote the emergence of FQ-resistant Campylobacter that can be transmitted to humans through the food chain. Recent studies have indicated that Campylobacter displays a hypermutable phenotype in response to in vivo treatment with FQ antimicrobials, resulting in the rapid emergence of resistant mutants. Distinct from other Gram-negative bacteria, the acquisition of FQ resistance in Campylobacter does not require stepwise accumulation of gyrA mutations and overexpression of efflux pumps, and is mainly mediated by single-step point mutations in gyrA in the presence of a constitutively expressed multidrug efflux pump, CmeABC. The simplicity of the resistance mechanisms may facilitate the rapid adaptation of Campylobacter to FQ treatment. The FQ-resistant Campylobacter mutants derived from chickens do not show a fitness cost in vivo and are ecologically competitive in the colonization of chickens even in the absence of antimicrobial selection pressure. These findings suggest that FQ-resistant Campylobacter may continue to persist regardless of antimicrobial usage, and highlight the need for extra effort to prevent the occurrence and spread of FQ-resistant Campylobacter in animal reservoirs.

Animals↗

Mutagen sensitivity as a susceptibility marker for endometriosis.

BACKGROUND: The mutagen sensitivity assay has been well established and widely used as a good independent risk predictor for developing cancers. Although endometriosis is considered a benign disorder, it exhibits several features similar to malignancy. The objectives of this study were to evaluate whether mutagen sensitivity can predict the risk of endometriosis development. METHODS: The subjects were women undergoing different surgical procedures due to different stages of endometriosis. Bleomycin was used as a mutagen, and the mutagen sensitivity of peripheral lymphocytes from women with and without endometriosis was determined by measuring chromatid breaks induced by bleomycin in short-term culture using cytogenetic analysis. RESULTS: The mean +/- SD (range) number of chromatid breaks per cell in women with and without endometriosis was 0.68 +/- 0.12 (0.50-0.94) and 0.52 +/- 0.10 (0.35-0.68), respectively. There was a significant difference with regard to mean chromatid breaks per cell between women with and without endometriosis (P < 0.001). On logistic regression analysis, the odds ratio (95% confidence interval) of chromatid breaks per cell was 5.80 (2.19-15.37, P < 0.001) for cases compared with controls. Yet, variables of interest including age, dysmenorrhoea, previous induced abortion and smoking in the home and workplace were not statistically correlated with chromatid breaks per cell. CONCLUSIONS: These preliminary data suggest that sensitivity to bleomycin-induced chromatid breaks in lymphocytes is associated with the risk of endometriosis development.

Abortion, Induced↗

In vivo selection of Campylobacter isolates with high levels of fluoroquinolone resistance associated with gyrA mutations and the function of the CmeABC efflux pump.

Enrofloxacin treatment of chickens infected with fluoroquinolone(FQ)-sensitive Campylobacter promoted the emergence of FQ-resistant Campylobacter mutants which propagated in the intestinal tract and recolonized the chickens. The recovered isolates were highly resistant to quinolone antibiotics but remained susceptible to non-FQ antimicrobial agents. Specific single-point mutations in the gyrA gene and the function of the CmeABC efflux pump were linked to the acquired FQ resistance. These results reveal that Campylobacter is hypermutable in vivo under the selection pressure of FQ and highlight the need for the prudent use of FQ antibiotics.

Animals↗

Critical role of multidrug efflux pump CmeABC in bile resistance and in vivo colonization of Campylobacter jejuni.

CmeABC functions as a multidrug efflux pump contributing to the resistance of Campylobacter to a broad range of antimicrobials. In this study, we examined the role of CmeABC in bile resistance and its contribution to the adaptation of Campylobacter jejuni in the intestinal tract of the chicken, a natural host and a major reservoir for Campylobacter. Inactivation of cmeABC drastically decreased the resistance of Campylobacter to various bile salts. Addition of choleate (2 mM) in culture medium impaired the in vitro growth of the cmeABC mutants but had no effect on the growth of the wild-type strain. Bile concentration varied in the duodenum, jejunum, and cecum of chicken intestine, and the inhibitory effect of the intestinal extracts on the in vitro growth of Campylobacter was well correlated with the total bile concentration in the individual sections of chicken intestine. When inoculated into chickens, the wild-type strain colonized the birds as early as day 2 postinoculation with a density as high as 10(7) CFU/g of feces. In contrast, the cmeABC mutants failed to colonize any of the inoculated chickens throughout the study. The minimum infective dose for the cmeABC mutant was at least 2.6 x 10(4)-fold higher than that of the wild-type strain. Complementation of the cmeABC mutants with a wild-type cmeABC allele in trans fully restored the in vitro growth in bile-containing media and the in vivo colonization to the levels of the wild-type strain. Immunoblotting analysis indicated that CmeABC is expressed and immunogenic in chickens experimentally infected with C. jejuni. Together, these findings provide compelling evidence that CmeABC, by mediating resistance to bile salts in the intestinal tract, is required for successful colonization of C. jejuni in chickens. Inhibition of CmeABC function may not only control antibiotic resistance but also prevent the in vivo colonization of pathogenic Campylobacter.

Animals↗

HLA-DRB1 allele polymorphisms in genetic susceptibility to esophageal carcinoma.

AIM: To probe into the genetic susceptibility of HLA-DRB1 alleles to esophageal carcinoma in Han Chinese in Hubei Province. METHODS: HLA-DRB1 allele polymorphisms were typed by polymerase chain reaction with sequence-specific primers(PCR-SSP) in 42 unrelated patients with esophageal cancer and 136 unrelated normal control subjects and the associated HLA-DRB1 allele was measured by nucleotide sequence analysis with PCR.SAS software was used in statistics. RESULTS: Allele frequency (AF) of HLA-DRB1*0901 was significantly higher in esophageal carcinoma patients than that in the normal controls (0.2500 vs 0.1397, P=0.028, the odds ratio 2.053, etiologic fraction 0.1282). After analyzed the allele nucleotide sequence of HLA-DRB1*0901 which approachs to the corresponded exon 2 sequence of the allele in genebank. There was no association between patients and controls in the rested HLA-DRB1 alleles. CONCLUSION: HLA-DRB1*0901 allele is more common in the patients with esophageal carcinoma than in the healthy controls, which is positively associated with the patients of Hubei Han Chinese. Individuals carrying HLA-DRB1*0901 may be susceptible to esophageal carcinoma.

Adult↗

Role of inducible nitric oxide synthase expression in aberrant crypt foci-adenoma-carcinoma sequence.

AIM: To investigate the expression of inducible nitric oxide synthase (iNOS) in aberrant crypt foci (ACF) -adenoma-carcinoma sequence and its relation with tumor cell apoptosis, proliferation and angiogenesis. METHODS: The expression of iNOS, proliferating cell nuclear antigen (PCNA) and microvessel density (MVD) in different stages of colorectal cancer were studied by immunohistochemical method from 30 normal tissues, 30 nonhyperplastic ACF, 30 hyperplastic ACF, 30 dysplastic ACF, 30 adenomas and 60 carcinomas. The apoptotic cells were detected by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) method using an Apop Tag in situ detection kit. RESULTS: The immunoreactivity of iNOS significantly increased in the transition from hyperplastic ACF to dysplastic ACF. This transition was associated with a significant decrease in the apoptotic index (AI) (0.73+/-0.37 vs 0.61+/-0.35, P<0.05) and significant increases in the PCNA labeling index (LI) (27.3+/-2.80 vs 40.3+/-3.11, P<0.01) and microvessel density (MVD) (55+/-11.5 vs 70+/-13.2, P<0.01). The expression of iNOS was in low levels and positively correlated with PCNA-LI (r=0.812, P<0.01) and MVD (r=0.863, P<0.01) during transition from normal mucosa to nonhyperplastic ACF and hyperplastic ACF. The expression of iNOS was in high levels and positively correlated with AI (r=0.901, P<0.01) after transition from hyperplastic ACF to dysplastic ACF, adenoma and carcinoma. CONCLUSION: The results suggest that the transition from hyperplastic ACF to dysplastic ACF may be a crucial step in the ACF-adenoma-carcinoma sequence, in which iNOS plays an important role by regulating tumor cell apoptosis, proliferation and angiogenesis.

Adenoma↗

Glutathione S-transferase M1 and T1 genotypes and endometriosis risk: a case-controlled study.

OBJECTIVE: To investigate the correlation between glutathione S-transferase (GST) M1 and T1 genotypes and endometriosis risk (EM). METHODS: Polymerase chain reaction (PCR) technique was used to detect the presence or absence of the GSTM1 and GSTT1 genes in genomic DNA isolated from the blood samples of 68 Han Chinese women with endometriosis and 28 without endometriosis. RESULTS: The frequencies of GSTM1 and GSTT1 null genotypes in women with endometriosis were 0.721 (49/68) and 0.779 (53/68), respectively, and in women without endometriosis were 0.429 (12/28) and 0.321 (9/28), respectively. There was a significant difference with regard to the frequencies of GSTM1 and GSTT1 null genotypes between the women with and without endometriosis (P < 0.01). Furthermore, the frequencies of GSTM1 and GSTT1 null genotypes were significantly higher in the patients with stage III and IV endometriosis [0.731 (38/52) and 0.788 (41/52), respectively] than in women without endometriosis (P < 0.01), and the frequency of GSTT1 null genotype was statistically higher in patients with stage I and II endometriosis [0.75 (12/16)] than in the women without endometriosis (P < 0.01). No correlation between GSTM1 and GSTT1 null genotypes and age, induced abortion or dysmenorrhea was detected in this study (P > 0.05). CONCLUSION: GSTM1 and GSTT1 null genotypes may be risk factors for the development of endometriosis.

Adult↗

Evolution of phenylalanyl-tRNA synthetase by domain losing.

The gene duplication, fusion and horizontal transfer are the frequent events during evolution of many proteins, including the aminoacyl-tRNA synthetases (AARSs). However, in this work, it was shown that the main event during evolution of phenylalanyl-tRNA synthetase (PheRS) is a domain loss, and the function/activity of PheRS is not affected by domain losing. Generally, the size of genome and number of genes are increased during evolution from bacteria to eukaryote, but the interesting thing is that the type and number of PheRS domains in eukaryote are obviously less than those in bacteria. The evolution of PheRS by domain losing seems to be related to the functional evolution of some AARSs from the multiple specificities to the single specificity.

Archaea↗

Hot-fluid annealing for crystalline titanium dioxide nanoparticles in stable suspension.

Titanium dioxide (TiO(2)) nanoparticles were synthesized by controlled hydrolysis of titanium alkoxide in reverse micelles in a hydrocarbon solvent. Upon annealing in situ in the presence of the micelles at temperatures considerably lower than those required for the traditional calcination treatment in the solid state, the TiO(2) nanoparticles became highly crystalline but still maintained the same physical parameters and remained in a stable suspension. Thus, the method has allowed the preparation of crystalline TiO(2) nanoparticles that are monodispersed in the same way as they are initially produced in the microemulsion. Effects of the fluid properties on the crystallization of nanoparticles are discussed.

Journal Article↗