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Biomedical subjects

Min Yao

Publications and source records attributed to Min Yao.

At least 19 recordsLinked to original sources
PubMed2007

The effects of second-hand smoke on biological processes important in atherogenesis.

BACKGROUND: Atherosclerosis is the leading cause of death in western societies and cigarette smoke is among the factors that strongly contribute to the development of this disease. The early events in atherogenesis are stimulated on the one hand by cytokines that chemoattract leukocytes and on the other hand by decrease in circulating molecules that protect endothelial cells (ECs) from injury. Here we focus our studies on the effects of "second-hand" smoke on atherogenesis. METHODS: To perform these studies, a smoking system that closely simulates exposure of humans to second-hand smoke was developed and a mouse model system transgenic for human apoB100 was used. These mice have moderate lipid levels that closely mimic human conditions that lead to atherosclerotic plaque formation. RESULTS: "Second-hand" cigarette smoke decreases plasma high density lipoprotein levels in the blood and also decreases the ratios between high density lipoprotein and low density lipoprotein, high density lipoprotein and triglyceride, and high density lipoprotein and total cholesterol. This change in lipid profiles causes not only more lipid accumulation in the aorta but also lipid deposition in many of the smaller vessels of the heart and in hepatocytes. In addition, mice exposed to smoke have increased levels of Monocyte Chemoattractant Protein-1 in circulation and in the heart/aorta tissue, have increased macrophages in the arterial walls, and have decreased levels of adiponectin, an EC-protective protein. Also, cytokine arrays revealed that mice exposed to smoke do not undergo the switch from the pro-inflammatory cytokine profile (that develops when the mice are initially exposed to second-hand smoke) to the adaptive response. Furthermore, triglyceride levels increase significantly in the liver of smoke-exposed mice. CONCLUSION: Long-term exposure to "second-hand" smoke creates a state of permanent inflammation and an imbalance in the lipid profile that leads to lipid accumulation in the liver and in the blood vessels of the heart and aorta. The former potentially can lead to non-alcoholic fatty liver disease and the latter to heart attacks.

Adiponectin↗
PubMed2007

DNA recognition mechanism of the ONECUT homeodomain of transcription factor HNF-6.

Hepatocyte nuclear factor-6 (HNF-6), a liver-enriched transcription factor, controls the development of various tissues, such as the pancreas and liver, and regulates the expression of several hepatic genes. This protein belongs to the ONECUT class of homeodomain proteins and contains a bipartite DNA-binding domain composed of a single cut domain and a characteristic homeodomain. This transcription factor has two distinct modes of DNA binding and transcriptional activation that use different coactivators depending on the target gene. The crystal structure of the bipartite DNA-binding domain of HNF-6alpha complexed with the HNF-6-binding site of the TTR promoter revealed the DNA recognition mechanism of this protein. Comparing our structure with the DNA-free structure of HNF-6 or the structure of Oct-1, we discuss characteristic features associated with DNA binding and the structural basis for the dual mode of action of this protein, and we suggest a strategy for variability of transcriptional activation of the target gene.

Amino Acid Sequence↗
PubMed2006

Structural and mutational analyses of Drp35 from Staphylococcus aureus: a possible mechanism for its lactonase activity.

Drp35 is a protein induced by cell wall-affecting antibiotics or detergents; it possesses calcium-dependent lactonase activity. To determine the molecular basis of the lactonase activity, we first solved the crystal structures of Drp35 with and without Ca(2+); these showed that the molecule has a six-bladed beta-propeller structure with two calcium ions bound at the center of the beta-propeller and surface region. Mutational analyses of evolutionarily conserved residues revealed that the central calcium-binding site is essential for the enzymatic activity of Drp35. Substitution of some other amino acid residues for the calcium-binding residues demonstrated the critical contributions of Glu(48), Asp(138), and Asp(236) to the enzymatic activity. Differential scanning calorimetric analysis revealed that the loss of activity of E48Q and D236N, but not D138N, was attributed to their inability to hold the calcium ion. Further structural analysis of the D138N mutant indicates that it lacks a water molecule bound to the calcium ion rather than the calcium ion itself. Based on these observations and structural information, a possible catalytic mechanism in which the calcium ion and its binding residues play direct roles was proposed for the lactonase activity of Drp35.

Amino Acid Substitution↗
PubMed2006

The structure of Pyrococcus horikoshii 2'-5' RNA ligase at 1.94 A resolution reveals a possible open form with a wider active-site cleft.

Bacterial and archaeal 2'-5' RNA ligases, members of the 2H phosphoesterase superfamily, catalyze the linkage of the 5' and 3' exons via a 2'-5'-phosphodiester bond during tRNA-precursor splicing. The crystal structure of the 2'-5' RNA ligase PH0099 from Pyrococcus horikoshii OT3 was solved at 1.94 A resolution (PDB code 1vgj). The molecule has a bilobal alpha+beta arrangement with two antiparallel beta-sheets constituting a V-shaped active-site cleft, as found in other members of the 2H phosphoesterase superfamily. The present structure was significantly different from that determined previously at 2.4 A resolution (PDB code 1vdx) in the active-site cleft; the entrance to the cleft is wider and the active site is easily accessible to the substrate (RNA precursor) in our structure. Structural comparison with the 2'-5' RNA ligase from Thermus thermophilus HB8 also revealed differences in the RNA precursor-binding region. The structural differences in the active-site residues (tetrapeptide motifs H-X-T/S-X) between the members of the 2H phosphoesterase superfamily are discussed.

Crystallization↗
PubMed2006

Abdominal aortic aneurysm and cerebral aneurysm present different pathological evolutions and responses to pharmacological therapy.

Over-degradation of extracellular components by matrix metalloproteinases (MMPs) has been implicated as an important characteristic during the pathological evolution of the abdominal aortic aneurysm (AAA) and cerebral aneurysm (CA), which contribute to progressive dilation of vascular wall. However, mRNA and protein expression of local rennin-angiotensin system (RAS) components are found down-regulated in CA walls, which is contrary to long-holding concept that local RAS will be activated in response to increased hemodynamic stress and contributes to thickening of arterial wall. Similarly, MMPs inhibition by doxycycline effectively ameliorate AAA expansion in basic and clinical researches, but can not reduce the incidence of CA formation in rat. These evidences may suggest that suppression of RAS favors the regression of AAA, but at an increased risk of CA rupture. As the strategies of RAS blockade have became the optimal antihypertensive drugs of choice in clinical arena, the discrepant responses to pharmacologic intervention of AAA and CA should be received considerable attentions, due to their high prevalence in hypertensive population. Here we proposed that AAA and CA, outward remodeling of elastic and muscular arteries respectively, presented with different pathological evolutions and distinct responses to drug intervention, i.e., RAS and MMPs inhibition. It can not be excluded that the potentially deleterious effects of RAS inhibition on CA may be masked by the beneficial action of controlled blood pressure, and the propagation of CA will be exacerbated once suboptimal dose have been prescribed, or under the condition of stress, even drug withdrawal. If the paradoxical outcomes of these two kinds of arterial remodeling were proven true in basic research, clinical use of RAS blockade should be prudent in hypertensive patients, and routine procedures to detect the existence of CA should be considered. Therefore, in depth investigation in their responses to pharmacological approaches will provide us with more insights into the pathogenesis of arterial aneurysm.

Aorta, Abdominal↗
PubMed2006

Structural characterization of the Acetobacter xylinum endo-beta-1,4-glucanase CMCax required for cellulose biosynthesis.

Previous studies have demonstrated that endoglucanase is required for cellulose biosynthesis both in bacteria and plants. However, it has yet to be elucidated how the endoglucanases function in the mechanism of cellulose biosynthesis. Here we describe the crystal structure of the cellulose biosynthesis-related endo-beta-1,47-glucanase (CMCax; EC 3.2.1.4) from the cellulose-producing Gramnegative bacterium, Acetobacter xylinum (= Gluconacetobacter xylinus), determined at 1.65-A resolution. CMCax falls into the glycoside hydrolase family 8 (GH-8), and the structure showed that the overall fold of the CMCax is similar to those of other glycoside hydrolases belonging to GH-8. Structure comparison with Clostridium thermocellum CelA, the best characterized GH-8 endoglucanase, revealed that sugar recognition subsite +3 is completely missing in CMCax. The absence of the subsite +3 leads to significant broadness of the cleft at the cellooligosaccharide reducing-end side. CMCax is known to be a secreted enzyme and is present in the culture medium. However, electron microscopic analysis using immunostaining clearly demonstrated that a portion of CMCax is localized to the cell surface, suggesting a link with other known membrane-anchored endoglucanases that are required for cellulose biosynthesis.

Amino Acid Sequence↗
PubMed2006

Structure of archaeal translational initiation factor 2 betagamma-GDP reveals significant conformational change of the beta-subunit and switch 1 region.

Archaeal/eukaryotic initiation factor 2 (a/eIF2) consists of alpha-, beta-, and gamma-subunits and delivers initiator methionine tRNA (Met-tRNA(i)) to a small ribosomal subunit in a GTP-dependent manner. The structures of the aIF2betagamma (archaeal initiation factor 2 betagamma) heterodimeric complex in the apo and GDP forms were analyzed at 2.8- and 3.4-A resolution, respectively. The results showed that the N-terminal helix and the central helix-turn-helix domain of the beta-subunit bind to the G domain of the gamma-subunit but are distant from domains 2 and 3, to which the alpha-subunit and Met-tRNA(i) bind. This result is consistent with most of the previous analyses of eukaryotic factors, and thus indicates that the binding mode is essentially conserved among a/eIF2. Comparison with the uncomplexed structure showed significant differences between the two forms of the beta-subunit, particularly the C-terminal zinc-binding domain, which does not interact with the gamma-subunit and was suggested previously to be involved in GTP hydrolysis. Furthermore, the switch 1 region in the gamma-subunit, which is shown to be responsible for Met-tRNA(i) binding by mutational analysis, is moved away from the nucleotide through the interaction with highly conserved R87 in the beta-subunit. These results implicate that conformational change of the beta-subunit facilitates GTP hydrolysis by inducing the conformational change of the switch 1 region toward the off state.

Amino Acid Sequence↗
PubMed2006

Dynamic alteration of telomerase expression and its diagnostic significance in liver or peripheral blood for hepatocellular carcinoma.

AIM: To investigate the dynamic alteration of telomerase expression during development of hepatocellular carcinoma (HCC) and its diagnostic implications in liver tissues or peripheral blood mononuclear cells for HCC. METHODS: Dynamic expressions of liver telomerase during malignant transformation of hepatocytes were observed in Sprague-Dawly (SD) rats fed with 0.05% of 2-fluoenyacetamide (2-FAA). Total RNA and telomerase were extracted from rat or human liver tissues. The telomerase activities in livers and in circulating blood were detected by a telomeric repeat amplification protocol-enzyme-linked immunosorbent assay (TRAP-ELISA), and its diagnostic value was investigated in patients with benign or malignant liver diseases. RESULTS: The hepatoma model displayed the dynamic expression of hepatic telomerase during HCC development. The telomerase activities were consistent with liver total RNA levels (r = 0.83, P<0.01) at the stages of degeneration, precancerosis, and cancerization of hepatocytes. In HCC patients, the telomerase levels in HCC tissues were significantly higher than in their adjacent non-cancerous tissues, but liver total RNA levels were lower in the former than in the latter. Although the circulating telomerase of HCC patients was abnormally expressed among patients with chronic liver diseases, the telomerase activity was a non-specific marker for HCC diagnosis, because the incidence was 15.7% in normal control, 25% in chronic hepatitis, 45.9% in liver cirrhosis, and 85.2% in HCC, respectively when absorbance value of telomerase activity was more than 0.2. If the value was over 0.6, the incidence was 60% in HCC group and 0% in any of the others (P<0.01) except in two cases with liver cirrhosis. However, the combination of circulating telomerase with serum alpha-fetoprotein level could increase the positive rate and the accuracy (92.6%, 125 of 135) of HCC diagnosis. CONCLUSION: The overexpression of telomerase is associated with HCC development, and its abnormality in liver tissues or in peripheral blood could be a useful marker for diagnosis and prognosis of HCC.

2-Acetylaminofluorene↗
PubMed2006

Comparison of drug eluting stents with bare metal stents in daily practice for bifurcation lesions in Chinese patients.

BACKGROUND: Recently, numerous randomized and controlled trials have demonstrated great advantages of drug eluting stents (DES) with respect to significant reduction of restenosis and recurrence of symptoms and improvement of clinical outcomes after percutaneous coronary intervention (PCI). Little is known about the comparative effects between DES and bare metal stents (BMS) for bifurcation angioplasty in the Chinese population. We compared the inpatient and 7-month follow-up outcomes between DES and BMS for the treatment of bifurcation lesions. METHODS: From April 2004 to October 2005, 291 Chinese patients [85.9% male, mean age (57.8 +/- 10.4) years] underwent DES (387 lesions) and/or BMS (297 lesions) implantation for bifurcation lesions. Clinical and angiographic follow-up was performed at 7 months. RESULTS: Compared with BMS group, patients in DES group had significantly lower rates of restenosis at main branch (9.5% vs 28.7%, P < 0.001) or side branch (14.5% vs 37.0%, P < 0.001) and major adverse cardiac events (MACE) (14.0% vs 26.3%, P = 0.000). The occurrence rate of late in-stent thrombosis did not differ between the two groups in both main (0.8% vs 0, P = 0.224) and side branches (1.4% vs 0, P = 0.198). Target lesion revascularization (TLR) was less frequent in DES group for main branch (8.3% vs 21.3%, P < 0.001) and for side branch (7.6% vs 23.5%, P < 0.001). Multivariate regression analysis revealed that total stent length (OR = 1.029, P = 0.01), postprocedural in-stent minimum lumen diameter (OR = 0.476, P = 0.03) and stent type (OR = 3.988, P = 0.0001) were independent predictors of TLR for main branch. Prior history of coronary intervention (OR = 2.424, P = 0.041), angulated lesion (OR = 2.337, P = 0.033), postdilation (OR = 0.267, P = 0.035) and stent type (DES vs BMS, OR = 5.459, P = 0.000) were independent predictors of TLR for side branch. CONCLUSION: The implantation of DES may be associated with greater reduction of restenosis and TLR than BMS in bifurcations angioplasty.

Adult↗
PubMed2006

Activation of sterol regulatory element-binding proteins (SREBPs) is critical in IL-8-induced angiogenesis.

Angiogenesis is essential in many physiological and pathological processes and can be stimulated by many different factors. To better understand and to manipulate this process more effectively, it would be beneficial to identify molecules common to the signaling pathways stimulated by different classes of angiogenic factors. Sterol regulatory element-binding proteins (SREBPs) are involved in the metabolism of cholesterol and fatty acids, molecules that are critical in membrane biology, and hence, many of the processes involved in angiogenesis. Here, we show that angiogenic factors of different families, such as basic fibroblast growth factor, thrombin, and interleukin (IL)-8, stimulate SREBP activation, whereas nonangiogenic factors, such as transforming growth factor-beta1, do not. We focused our detailed studies on IL-8 in vitro and in vivo, as this chemokine is also involved in inflammation and hence, has the potential to be critical in inflammation-induced angiogenesis, a process common to many diseases. Using human microvascular endothelial cells, a rabbit skin wound-healing model, and the chorioallantoic membrane assay, we show that IL-8 stimulates the activation of SREBP-1 and -2, and this activation is specific and receptor-mediated. SREBP activation leads to activation of RhoA through 3-hydroxy-3-methylglutaryl CoA reductase. RhoA is a small guanosinetriphosphatase, important in cytoskeletal functions, which in turn, are critical in many of the cellular processes needed for angiogenesis. Given that diverse, angiogenic factors use different cell-surface receptors, identification of this common step in the signal-transduction pathway provides the opportunity for novel approaches for prevention and treatment of diseases involving abnormal angiogenesis.

Cell Movement↗
PubMed2006

A comparison of angiographic and clinical outcomes after sirolimus-eluting versus paclitaxel-eluting stents for the treatment of in-stent restenosis.

BACKGROUND: In-stent restenosis (ISR) remains a challenge for interventional cardiologists. Some data suggest that drug-eluting stents (DES) represent a promising new option for the treatment of patients with ISR. Currently, 2 DES platforms are available [sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES)], but the superiority of either approach for treating ISR has not been convincingly demonstrated. The aim of the present study was to retrospectively compare angiographic and clinical outcomes after treatment of ISR with SES or PES in a series of consecutive patients with ISR. METHODS: A total of 745 consecutive patients were treated with bare metal stents from April 12, 2004 to December 31, 2004 in our center. Of these, clinically driven target lesion revascularization (TLR) was performed in 54 ISR from 54 patients at 7 months. Of the 54 patients with ISR, 36 received SES and 18 received PES. Follow-up included angiography and assessment of clinical outcome, both performed 7 months after DES implantation. RESULTS: There were no significant differences in baseline clinical data (including medication usage and lesion characteristics) between the two groups. Except for overlapping of multiple stents, procedural parameters were also similar in both groups. Seven-month angiographic follow-up showed that the binary restenosis rate was higher in patients treated with PES than that in patients treated with SES (in-stent binary restenosis: 27.8% vs 5.6%, P < 0.023; In-segment binary restenosis: 44.4% vs 13.9%, P < 0.014). Major adverse cardiac events (MACE) occurring during hospitalization or during the follow-up period including thrombosis and TLR was similar in both groups (22.2% vs 8.3%, P > 0.05). CONCLUSIONS: Results from this small sample size, retrospective, single-center study showed that SES might be superior to PES in treating ISR because of lower 7-month restenosis rates (both in-stent and in-segment binary restenosis) with no increased incidence of MACE.

Adult↗
PubMed2006

Ammonia channel couples glutaminase with transamidase reactions in GatCAB.

The formation of glutaminyl transfer RNA (Gln-tRNA(Gln)) differs among the three domains of life. Most bacteria employ an indirect pathway to produce Gln-tRNA(Gln) by a heterotrimeric glutamine amidotransferase CAB (GatCAB) that acts on the misacylated Glu-tRNA(Gln). Here, we describe a series of crystal structures of intact GatCAB from Staphylococcus aureus in the apo form and in the complexes with glutamine, asparagine, Mn2+, and adenosine triphosphate analog. Two identified catalytic centers for the glutaminase and transamidase reactions are markedly distant but connected by a hydrophilic ammonia channel 30 A in length. Further, we show that the first U-A base pair in the acceptor stem and the D loop of tRNA(Gln) serve as identity elements essential for discrimination by GatCAB and propose a complete model for the overall concerted reactions to synthesize Gln-tRNA(Gln).

Adenosine Diphosphate↗
PubMed2006

Crystal structure of hypothetical protein TTHB192 from Thermus thermophilus HB8 reveals a new protein family with an RNA recognition motif-like domain.

We have determined the crystal structure of hypothetical protein TTHB192 from Thermus thermophilus HB8 at 1.9 A resolution. This protein is a member of the Escherichia coli ygcH sequence family, which contains approximately 15 sequence homologs of bacterial origin. These homologs have a high isoelectric point. The crystal structure reveals that TTHB192 consists of two independently folded domains, and that each domain exhibits a ferredoxin-like fold with a four-stranded antiparallel beta-sheet packed on one side by alpha-helices. These two tandem domains face each other to generate a beta-sheet platform. TTHB192 displays overall structural similarity to Sex-lethal protein and poly(A)-binding protein fragments. These proteins have RNA binding activity which is supported by a beta-sheet platform formed by two tandem repeats of an RNA recognition motif domain with signature sequence motifs on the beta-sheet surface. Although TTHB192 does not have the same signature sequence motif as the RNA recognition motif domain, the presence of an evolutionarily conserved basic patch on the beta-sheet platform could be functionally relevant for nucleic acid-binding. This report shows that TTHB192 and its sequence homologs adopt an RNA recognition motif-like domain and provides the first testable functional hypothesis for this protein family.

Amino Acid Motifs↗
PubMed2006

Structure of the catalytic nucleotide-binding subunit A of A-type ATP synthase from Pyrococcus horikoshii reveals a novel domain related to the peripheral stalk.

H(+)-transporting ATP synthase is a multi-subunit enzyme involved in the production of ATP, which is an essential molecule for living organisms as a source of energy. Archaeal A-type ATPase (A-ATPase) is thought to act as a functional ATP synthase in archaea and is thought to have chimeric properties of F-ATPase and V-ATPase. Previous structural studies of F-ATPase indicated that the major nucleotide-binding subunits alpha and beta consist of three domains. The catalytic nucleotide-binding subunit A of V/A-ATPase contains an insertion of about 90 residues which is absent from the F(1)-ATPase beta subunit. Here, the first X-ray structure of the catalytic nucleotide-binding subunit A of an A(1)-ATPase is described, determined at 2.55 A resolution. A(1)-ATPase subunit A from Pyrococcus horikoshii consists of four domains. A novel domain, including part of the insertion, corresponds to the 'knob-like structure' observed in electron microscopy of A(1)-ATPase. Based on the structure, it is highly likely that this inserted domain is related to the peripheral stalk common to the A- and V-ATPases. The arrangement of this inserted domain suggests that this region plays an important role in A-ATPase as well as in V-ATPase.

Amino Acid Sequence↗
PubMed2006

A single center investigation of bare-metal or drug-eluting stent restenosis from 1633 consecutive Chinese Han ethnic patients.

BACKGROUND: Stents are widely used in China but the clinical impression is somehow that restenosis is less common because of the lower prevalence of coronary artery disease (CAD) and associated risk factors in Chinese populations. However, no large-sample published studies are available on angiographic stent restenosis including those of bare-metal stent (BMS) or drug-eluting stent (DES) in Chinese Han ethnic population. METHODS: A total of 1633 consecutive patients with CAD who had undergone coronary stenting, quantitative coronary angiography (QCA) were retrospectively studied. At the time of stent implantation and at 7 months post-stenting 675 patients had a follow-up angiography. Statistical analysis was made with the chi-square test for categorical variables, unpaired t test for continuous variables, univariate or multivariate regression for baseline and angiographic characteristics and the Kaplan-Meier method for rate of target lesion revascularization (TLR). RESULTS: Stent restenosis was defined as > or = 50% diameter stenosis in the dilated segment. A total of 675 patients with 1074 lesions were subjected to angiographic follow-up for 7 months on average. Of these lesions, 448 were implanted with BMS whereas 626 lesions with DES. At 7 months, bare-metal in-stent restenosis occurred in 148 lesions (33.0%), and bare metal in-segment restenosis in 155 lesions (34.6%) in contrast to drug-eluting in-stent restenosis in 48 lesions (7.7%) and drug-eluting in-segment restenosis in 73 lesions (11.7%) (P < 0.001 compared with BMS respectively). Late loss in both in-stent and in segment was higher in BMS than in DES groups [(1.00 +/- 0.69) vs (0.28 +/- 0.52); (0.78 +/- 0.71) vs (0.21 +/- 0.52), P < 0.001 respectively]. Angulated lesion, lesion length, pre-procedural minimal luminal diameter (MLD), and BMS were independent predictors for TLR, (P < 0.01 respectively), whereas current smoker, ostial lesion, and stent overlapping, post-procedure in-stent MLD, lesion length, and stent types were independent predictors for in-segment restenosis (P < 0.01 respectively). Standard coronary risk factors such as hypertension, hyperlipidemia, diabetes, and history of CAD were not associated with a higher rate of restenosis caused by BMS or DES implantation in our Chinese Han ethnic population. CONCLUSIONS: Coronary stenting including BMS or DES implantation in Chinese Han ethnic patients is associated with a restenosis rate comparable to that demonstrated in previous studies from the western countries, and predictors of stent restenosis are somehow different from those in the western population.

Adult↗