Hydrogen sulfide inhibits the renal fibrosis of obstructive nephropathy

Hydrogen sulfide has recently been found decreased in chronic kidney disease. Here we determined the effect and underlying mechanisms of hydrogen sulfide on a rat model of unilateral ureteral obstruction. Compared with normal rats, obstructive injury decreased the plasma hydrogen sulfide level. Cystathionine-β-synthase, a hydrogen sulfide-producing enzyme, was dramatically reduced in the ureteral obstructed kidney, but another enzyme cystathionine-γ-lyase was increased. A hydrogen sulfide donor (sodium hydrogen sulfide) inhibited renal fibrosis by attenuating the production of collagen, extracellular matrix, and the expression of α-smooth muscle actin. Meanwhile, the infiltration of macrophages and the expression of inflammatory cytokines including interleukin-1β, tumor necrosis factor-α, and monocyte chemoattractant protein-1 in the kidney were also decreased. In cultured kidney fibroblasts, a hydrogen sulfide donor inhibited the cell proliferation by reducing DNA synthesis and downregulating the expressions of proliferation-related proteins including proliferating cell nuclear antigen and c-Myc. Further, the hydrogen sulfide donor blocked the differentiation of quiescent renal fibroblasts to myofibroblasts by inhibiting the transforming growth factor-β1-Smad and mitogen-activated protein kinase signaling pathways. Thus, low doses of hydrogen sulfide or its releasing compounds may have therapeutic potentials in treating chronic kidney disease

The Interesting Influence of Nanosprings on the Viscoelasticity of Elastomeric Polymer Materials: Simulation and Experiment

Among all carbon nanostructured materials, helical nanosprings or nanocoils have attracted particular interest as a result of their special mechanical behavior. Here, carbon nanosprings are used to adjust the viscoelasticity and reduce the resulting hysteresis loss (HL) of elastomeric polymer materials. Two types of nanospring‐filled elastomer composites are constructed as follows: system I is obtained by directly blending polymer chains with nanosprings; system II is composed of the self‐assembly of a tri‐block structure such as chain‐nanospring‐chain. Coarse‐grained molecular dynamics simulations show that the incorporation of nanosprings can improve the mechanical strength of the elastomer matrix through nanoreinforcement and considerably decrease the hysteresis loss. This finding is significant for reducing fuel consumption and improving fuel efficiency in the automobile tire industry. Furthermore, it is revealed that the spring constant of nanosprings and the interfacial chemical coupling between chains and nanosprings both play crucial roles in adjusting the viscoelasticity of elastomers. It is inferred that elastomer/carbon nanostructured materials with good flexibility and reversible mechanical response (carbon nanosprings, nanocoils, nanorings, and thin graphene sheets) have both excellent mechanical and low HL properties; this may open a new avenue for fabrication of high performance automobile tires and facilitate the large‐scale industrial application of these materials. Carbon nanosprings are found to have the capability to tune the mechanical and viscoelastic properties of elastomeric polymer materials. It is inferred that elastomer/carbon nanostructured materials with good flexibility and reversible mechanical response (i.e., carbon nanosprings, nanocoils, nanorings, and thin graphene sheets) have both excellent mechanical properties and low hysteresis loss.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/96669/1/adfm_201201438_sm_suppl.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/96669/2/1156_ftp.pd

A genetic diversity assessment of starch quality traits in rice landraces from the Taihu basin, China

AbstractThere are nearly 1000 rice landrace varieties in the Taihu basin, China. To assess the genetic diversity of the rice, 24 intragenic molecular markers (representing 17 starch synthesis-related genes) were investigated in 115 Taihu basin rice landraces and 87 improved cultivars simultaneously. The results show that the average genetic diversity and polymorphism information content values of the landraces were higher than those of improved cultivars. In total, 41 and 39 allele combinations (of the 17 genes) were derived from the landraces and improved cultivars, respectively; only two identical allele combinations were found between the two rice variety sources. Cluster analysis, based on the molecular markers, revealed that the rice varieties could be subdivided into five groups and, within these, the japonica improved rice and japonica landrace rice varieties were in two separate groups. According to the quality reference criteria to classify the rice into grades, some of the landraces were found to perform well, in terms of starch quality. For example, according to NY/T595-2002 criteria from the Ministry of Agriculture of China, 25 and 33 landraces reached grade 1, in terms of their apparent amylose content and gel consistency. The varieties that had outstanding quality could be used as breeding materials for rice quality breeding programs in the future. Our study is useful for future applications, such as genetic diversity studies, the protection of rice variety and improvment of rice quality in breeding programs

RNA interference of argininosuccinate synthetase restores sensitivity to recombinant arginine deiminase (rADI) in resistant cancer cells

Background Sensitivity of cancer cells to recombinant arginine deiminase (rADI) depends on expression of argininosuccinate synthetase (AS), a rate- limiting enzyme in synthesis of arginine from citrulline. To understand the efficiency of RNA interfering of AS in sensitizing the resistant cancer cells to rADI, the down regulation of AS transiently and permanently were performed in vitro, respectively. Methods We studied the use of down-regulation of this enzyme by RNA interference in three human cancer cell lines (A375, HeLa, and MCF-7) as a way to restore sensitivity to rADI in resistant cells. The expression of AS at levels of mRNA and protein was determined to understand the effect of RNA interference. Cell viability, cell cycle, and possible mechanism of the restore sensitivity of AS RNA interference in rADI treated cancer cells were evaluated. Results AS DNA was present in all cancer cell lines studied, however, the expression of this enzyme at the mRNA and protein level was different. In two rADI-resistant cell lines, one with endogenous AS expression (MCF-7 cells) and one with induced AS expression (HeLa cells), AS small interference RNA (siRNA) inhibited 37-46% of the expression of AS in MCF- 7 cells. ASsiRNA did not affect cell viability in MCF-7 which may be due to the certain amount of residual AS protein. In contrast, ASsiRNA down- regulated almost all AS expression in HeLa cells and caused cell death after rADI treatment. Permanently down-regulated AS expression by short hairpin RNA (shRNA) made MCF-7 cells become sensitive to rADI via the inhibition of 4E-BP1-regulated mTOR signaling pathway. Conclusions Our results demonstrate that rADI-resistance can be altered via AS RNA interference. Although transient enzyme down- regulation (siRNA) did not affect cell viability in MCF-7 cells, permanent down- regulation (shRNA) overcame the problem of rADI-resistance due to the more efficiency in AS silencing

Association between Virulence Factors and TRAF1/4-1BB/Bcl-xL

Objective. CagA+/vacAs1+/vacAm1+ Helicobacter pylori upregulates the expression of tumor necrosis factor receptor–associated factor 1 (TRAF1), tumor necrosis factor receptor superfamily member 9 (4-1BB), and B-cell lymphoma-extra large (Bcl-xL) in human gastric epithelial cells. We investigated the correlation between cagA/vacAs1/vacAm1 and TRAF1/4-1BB/Bcl-xL expression in gastric mucosal tissue of patients with gastric disorders. Methods. We collected gastric mucosa samples from 35 chronic, nonatrophic gastritis (CG) patients, 41 atrophic gastritis patients, 44 intestinal metaplasia with atypical hyperplasia (IM) patients, and 28 gastric carcinoma (Ca) patients. The expression of  TRAF1, 4-1BB, and Bcl-xL was determined using western blotting. The expression of cagA, vacAs1, and vacAm1 in H. pylori was examined with polymerase chain reaction. Results. The expression of TRAF1, 4-1BB, and Bcl-xL was significantly upregulated in IM and Ca patients (P<0.05 compared with CG). There were more cases of cagA+/vacAs1+/vacAm1+ H. pylori infection in samples with elevated TRAF1, 4-1BB, or Bcl-xL expression (P<0.05). Additionally, there were a remarkably large number of samples with upregulated TRAF1/4-1BB/Bcl-xL expression in cases of cagA+/vacAs1+/vacAm1+ H. pylori infection (44 cases, 67.7%; P<0.05). Conclusions. The pathogenesis of IM and Ca may be promoted by cagA+/vacAs1+/vacAm1+ H. pylori, possibly via upregulated TRAF1, 4-1BB, and Bcl-xL in gastric mucosal tissue

PinX1 regulation of telomerase activity and apoptosis in nasopharyngeal carcinoma cells

<p>Abstract</p> <p>Background</p> <p>Human interacting protein X1 (PinX1) has been identified as a critical telomerase inhibitor and proposed to be a putative tumor suppressor gene. Loss of PinX1 has been found in a large variety of malignancies, however, its function in inhibiting telomerase activity of tumor cells is not well documented. Here we show that PinX1 is essential for down-regulation telomerase activity of nasopharyngeal carcinoma.</p> <p>Methods</p> <p>Expression vectors of human PinX1 (pEGFP-C3-PinX1) and its small interfering RNA (PinX1-FAM-siRNA) were constructed and transfected into NPC. Their effects on mRNA of telomerase catalytic subunit (hTERT), telomerase activity, cell proliferation, cell migration, wound healing, cell cycles and apoptosis were examined using semi-quantitative RT-PCR, stretch PCR, MTT assay, Transwell, scratch assay and flow cytometry, respectively.</p> <p>Results</p> <p>Transfection of pEGFP-C3-PinX1 and PinX1-FAM-siRNA increased and reduced PinX1 mRNA by 1.6-fold and 70%, respectively. Over-expression of PinX1 decreased hTERT mRNA by 21%, reduced telomerase activity, inhibited cell growth, migration and wound healing ability, arrested cells in G0/G1 phase, and increased apoptotic index. In contrast, down-regulation of PinX1 did not alter the above characteristics.</p> <p>Conclusions</p> <p>PinX1 may play important roles in NPC proliferation, migration and apoptosis and has application potential in tumor-targeted gene therapy.</p

Isolation and characterization of a genotype 4 Hepatitis E virus strain from an infant in China

In the present study, a genotype 4 HEV strain was identified in the fecal specimen from a seven months old infant with no symptom of hepatitis in Shanghai Children's hospital. The full capsid protein gene (ORF2) sequence of this strain was determined by RT-PCR method. Sequence analysis based on the full ORF2 sequence indicated that this HEV strain shared the highest sequence identity (97.6%) with another human HEV strain isolated from a Japanese patient who was infected by genotype 4 HEV during traveling in Shanghai. Phylogenetic analysis showed that this genotype 4 HEV was phylogenetically far from the genotype 4 HEV strain that was commonly prevalent in Shanghai swine group, suggesting that this strain may not come from swine group and not involved in zoonotic transmission in this area

Purification, Characterization and Antitumor Activities of a New Protein from Syngnathus acus, an Officinal Marine Fish

Discovery and development of new antitumor agents from abundant marine fish are attracting an increasing interest. In the present study, we extracted and purified a novel antitumor protein Syngnathusin from the whole body of Syngnathus acus L., a precious marine fish traditionally used for tumors. Syngnathusin was comprised of 16 kinds of amino acids, mainly acidic amino acids. Its molecular weight was 67.3 kDa and its isoelectric point was 4.57. The N-terminal amino acid sequence of Syngnathusin was determined to be Lys-Arg-Asp-Leu-Gly-Phe-Val-Asp-Glu-Ile-Ser-Ala-His-Tyr and showed no significant homology with the known proteins. Syngnathusin could significantly inhibit the growth of A549 and CCRF-CEM cells. However, the obvious proliferation inhibition against human non-tumor cell lines was not observed. Flow cytometry, morphologic assessment and comet assay revealed that Syngnathusin could induce apoptosis in A549 and CCRF-CEM cells and strongly cooperated with MTX. Syngnathusin could inhibit the growth of S180 tumor transplanted in mice. Syngnathusin may be developed as a novel, selective and effective antineoplastic agent

Influence of ADAM10 Polymorphisms on Plasma Level of Soluble Receptor for Advanced Glycation End Products and The Association With Alzheimer’s Disease Risk

To determine the role of A disintegrin and metalloproteinase 10 (ADAM10) in genetic susceptibility to Alzheimer’s disease (AD) in a representative Chinese sample, we genotyped 362 AD patients and 370 healthy controls for the rs514049A/C and rs653765C/T polymorphisms in the ADAM10 promoter using the SNaPshot technique. We also examined the potential impact of these polymorphisms on the plasma level of soluble receptor for advanced glycation end products (sRAGE), a decoy receptor whose reduction has been associated with a higher risk of AD. Additionally, a meta-analysis was performed using the present study and the largest GWAS from the International Genomics of Alzheimer’s Project (IGAP). No significant differences were found in the distributions of genotypes or alleles between AD patients and control subjects. However, age-at-onset stratification analysis revealed that there were significant differences in the genotypes (P = 0.015) and alleles (P = 0.006) of the rs653765 SNP. Furthermore, patients with the rs653765 CC genotype showed a lower ADAM10 level and a faster cognitive deterioration than those in patients with the CT/TT genotype in late-onset AD (LOAD), and the rs653765 CC polymorphism was able to regulate the production of the ADAM10 substrate sRAGE. In contrast, the rs514049 polymorphism was not statistically associated with AD. In the meta-analysis, we observed that both rs514049 (A allele vs. C allele, P = 0.002) and rs653765 (C allele vs. T allele, P = 0.004) were associated with AD risk. The present study indicated that the rs653765 polymorphism might be associated with the risk and development of LOAD; in particular, the risk genotype, CC, may decrease the expression of ADAM10, influencing the plasma levels of sRAGE, and thus may be correlated with the clinical progression of AD