Potential biomarkers: The hypomethylation of cg18949415 and cg22193385 sites in colon adenocarcinoma.

Overall cancer hypomethylation had been identified in the past, but it is not clear exactly which hypomethylation site is the more important for the occurrence of cancer. To identify key hypomethylation sites, we studied the effect of hypomethylation in twelve regions on gene expression in colon adenocarcinoma (COAD). The key DNA methylation sites of cg18949415, cg22193385 and important genes of C6orf223, KRT7 were found by constructing a prognostic model, survival analysis and random combination prediction a series of in-depth systematic calculations and analyses, and the results were validated by GEO database, immune microenvironment, drug and functional enrichment analysis. Based on the expression values of C6orf223, KRT7 genes and the DNA methylation values of cg18949415, cg22193385 sites, the least diversity increment algorithm were used to predict COAD and normal sample. The 100 % reliability and 97.12 % correctness of predicting tumor samples were obtained in jackknife test. Moreover, we found that C6orf223 gene, cg18949415 site play a more important role than KRT7 gene, cg22193385 site in COAD. In addition, we investigate the impact of key methylation sites on three-dimensional chromatin structure. Our results will be help for experimental studies and may be an epigenetic biomarker for COAD.

Single Amino Acid Substitutions Surrounding the Icosahedral Fivefold Symmetry Axis Are Critical for Alternative Receptor Usage of Foot-and-Mouth Disease Virus.

The integrins function as the primary receptor molecules for the pathogenic infection of foot-and-mouth disease virus (FMDV) in vivo, while the acquisition of a high affinity for heparan sulfate (HS) of some FMDV variants could be privileged to facilitate viral infection and expanded cell tropism in vitro. Here, we noted that a BHK-adapted Cathay topotype derivative (O/HN/CHA/93tc) but not its genetically engineered virus (rHN), was able to infect HS-positive CHO-K1 cells and mutant pgsD-677 cells. There were one or three residue changes in the capsid proteins of O/HN/CHA/93tc and rHN, as compared with that of their tissue-originated isolate (O/HN/CHA/93wt). The phenotypic properties of a set of site-directed mutants of rHN revealed that E83K of VP1 surrounding the fivefold symmetry axis was necessary for the integrin-independent infection of O/HN/CHA/93tc. L80 in VP2 was essential for the occurrence of E83K in VP1 during the adaptation of O/HN/CHA/93wt to BHK-21 cells. L80M in VP2 and D138G in VP1 of rHN was deleterious, which could be compensated by K83R of VP1 for restoring an efficient infection of integrin-negative CHO cell lines. These might have important implications for understanding the molecular and evolutionary mechanisms of the recognition and binding of FMDV with alternative cellular receptors.

An energy model for recognizing the prokaryotic promoters based on molecular structure.

Promoter is an important functional elements of DNA sequences, which is in charge of gene transcription initiation. Recognizing promoter have important help for understanding the relative life phenomena. Based on the concept that promoter is mainly determined by its sequence and structure, a novel statistical physics model for predicting promoter in Escherichia coli K-12 is proposed. The total energies of DNA local structure of sequence segments in the three benchmark promoter sequence datasets, the sole prediction parameter, are calculated by using principles from statistical physics and information theory. The better results are obtained. And a web-server PhysMPrePro for predicting promoter is established at http://202.207.14.87:8032/bioinformation/PhysMPrePro/index.asp, so that other scientists can easily get their desired results by our web-server.

Search for clinical predictors of good glycemic control in patients starting or intensifying oral hypoglycemic pharmacological therapy: A multicenter prospective cohort study.

AIMS: Our aim was to search for clinical predictors of good glycemic control in patients starting or intensifying oral hypoglycemic pharmacological therapy. METHODS: A multicenter, prospective cohort of 499 diabetic subjects was enrolled in this study: patients with newly diagnosed diabetes (NDM group) or poor glycemic control with oral antidiabetic drugs (OADs) (PDM group). All subjects then started or intensified OADs therapy and followed up for 91 days. Glycemic control was determined according to HbA1c at day 91 with HbA1c <7% considered good. RESULTS: The proportions of patients with good glycemic control after follow up for 91 days were 66.9% and 34.8% in NDM group and PDM group respectively. Logistic regression analysis showed that the change in GA at 28 days was the only predictor of good glycemic control in NDM patients (OR = 1.630, 95% CI 1.300-2.044, P < 0.001). In PDM patients, changes in GA at 28 days, CPI, baseline HbA1c, diabetic duration, and BMI were all independent predictors of good glycemic control (All P < 0.05). CONCLUSIONS: GA decline is a good predictor of future success in newly diagnosed patients. In patients intensifying therapy, beside GA decline, other individualized clinical characteristics should also be considered.

Characteristics of chemotherapy-induced diabetes mellitus in acute lymphoblastic leukemia patients / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Acute lymphocytic leukemia (ALL) is one of the most common malignancies, especially in young people. Combination chemotherapy for ALL typically includes corticosteroids (Kantarjian et al., 2000). Hyperglycemia is a well-recognized complication of corticosteroids, and chemotherapy-induced diabetes (CID) is not uncommon (27.5%-37.0%) during the treatment of ALL (Hsu et al., 2002; Weiser et al., 2004; Alves et al., 2007). Besides the effect of corticosteroids, potential factors triggering hyperglycemia in ALL also include direct infiltration of the pancreas by leukemia cells and β cell dysfunction induced by chemotherapeutic agents such as L-asparagine (Mohn et al., 2004).

Engineering Responses to Amino Acid Substitutions in the VP0- and VP3-Coding Regions of PanAsia-1 Strains of Foot-and-Mouth Disease Virus Serotype O.

The presence of sequence divergence through adaptive mutations in the major capsid protein VP1, and also in VP0 (VP4 and VP2) and VP3, of foot-and-mouth disease virus (FMDV) is relevant to a broad range of viral characteristics. To explore the potential role of isolate-specific residues in the VP0 and VP3 coding regions of PanAsia-1 strains in genetic and phenotypic properties of FMDV, a series of recombinant full-length genomic clones were constructed using Cathay topotype infectious cDNA as the original backbone. The deleterious and compensatory effects of individual amino acid substitutions at positions 4008 and 3060 and in several different domains of VP2 illustrated that the chain-based spatial interaction patterns of VP1, VP2, and VP3 (VP1-3), as well as between the internal VP4 and the three external capsid proteins of FMDV, might contribute to the assembly of eventually viable viruses. The Y2079H site-directed mutants dramatically induced a decrease in plaque size on BHK-21 cells and viral pathogenicity in suckling mice. Remarkably, the 2079H-encoding viruses displayed a moderate increase in acid sensitivity correlated with NH4Cl resistance compared to the Y2079-encoding viruses. Interestingly, none of all the 16 rescued viruses were able to infect heparan sulfate-expressing CHO-K1 cells. However, viral infection in BHK-21 cells was facilitated by utilizing non-integrin-dependent, heparin-sensitive receptor(s) and replacements of four uncharged amino acids at position 3174 in VP3 of FMDV had no apparent influence on heparin affinity. These results provide particular insights into the correlation of evolutionary biology with genetic diversity in adapting populations of FMDV.IMPORTANCE The sequence variation within the capsid proteins occurs frequently in the infection of susceptible tissue cultures, reflecting the high levels of genetic diversity of FMDV. A systematic study for the functional significance of isolate-specific residues in VP0 and VP3 of FMDV PanAsia-1 strains suggested that the interaction of amino acid side chains between the N terminus of VP4 and several potential domains of VP1-3 had cascading effects on the viability and developmental characteristics of progeny viruses. Y2079H in VP0 of the indicated FMDVs could affect plaque size and pathogenicity, as well as acid sensitivity correlated with NH4Cl resistance, whereas there was no inevitable correlation in viral plaque and acid-sensitive phenotypes. The high affinity of non-integrin-dependent FMDVs for heparin might be explained by the differences in structures of heparan sulfate proteoglycans on the surfaces of different cell lines. These results may contribute to our understanding of the distinct phenotypic properties of FMDV in vitro and in vivo.

Dose titration model and correlative factors analysis in Chinese patients with type-2 diabetes on basal insulin - results from an Observational Registry of Basal Insulin Treatment study.

INTRODUCTION: This study evaluates an insulin dose titration model and factors that impact insulin dose adjustment in Chinese adults with type-2 diabetes, who receive basal insulin in real-world settings. MATERIAL AND METHODS: A total of 19,894 patients from the ORBIT study were included. These patients were divided into four groups, according to the type of insulin dose adjustment: no insulin titration (group A), self-titration (group B), physician-led insulin titration (group C), and combined physician and patient-led insulin titration (group D). Data were collected and compared at baseline and after six months of treatment. RESULTS: A total of 12,865 patients completed the visits and were included in the analysis. Among these patients, 3187 (24.8%), 1971 (15.3%), 5165 (40.1%), and 2542 (19.8%) patients were included in groups A, B, C, and D, respectively. The multivariate logistic regression analysis revealed that the duration of diabetes, body mass index, microvascular complications, inpatient days, HbA1C level, and self-monitoring of blood glucose (SMBG) were positively correlated with insulin titration in group B, C, and D, compared with group A. The number of inpatient days and outpatient visits were positively correlated with dose adjustment for physician-led titration, while this was negatively correlated for self-titration. Self-titration encouraged by physicians and home blood glucose monitoring were positively correlated with self-titration and the combined physician and patient-led titration. CONCLUSIONS: High HbA1C level, SMBG, long disease duration, microvascular complications, and the encouragement of physicians while initiating insulin use prompt patients to perform dose adjustments in real-world settings.

Nrf2 mediates the protective effects of homocysteine by increasing the levels of GSH content in HepG2 cells.

Homocysteine (Hcy) and glutathione (GSH) are crucial reduction­oxidation mediators. The underlying mechanisms governing the effects of Hcy on GSH generation in the progression of alcoholic liver disease has so far received little attention. The present study hypothesized that the antioxidant transcriptional factor nuclear factor (erythroid­derived 2)­like 2 (Nrf2) may participate in Hcy­mediated regulation of GSH production in HepG2 human liver cancer cells. MTT assay was used to study the cytotoxicity of homocysteine, western blot analysis and immunofluorescence staining were used to determine the effect of Hcy on Nrf2 expression. Our data demonstrated that HepG2 cells exposed to exogenous levels of Hcy (0­100 µM) exhibited elevated GSH levels in a concentration­dependent manner. Furthermore, 4­hydroxynonenal (4­HNE)­induced cell injury was attenuated by Hcy; however, this protective effect was blocked by the GSH­production inhibitor buthionine sulfoximine. Hcy treatment was able to induce Nrf2 protein expression in HepG2 cells. Treatment with the Nrf2 activator tert­butylhydroquinone (0­100 µM) increased GSH expression in a concentration­dependent manner; however, Nrf2­siRNA abolished the Hcy­induced increase in GSH expression and cellular protection in 4­HNE­stressed HepG2 cells. In conclusion, the antioxidant transcriptional factor Nrf2 was demonstrated to mediate the Hcy­induced increase in GSH expression levels and cellular protection in HepG2 cells.

Glycated albumin is superior to glycated hemoglobin for glycemic control assessment at an early stage of diabetes treatment: A multicenter, prospective study.

AIMS: This study was to determine whether serum glycated albumin (GA) was a better indicator of glycemic control than hemoglobin A1c (HbA1c) when starting a new treatment regimen for type 2 diabetes. METHODS: Newly diagnosed type 2 diabetes patients, or patients who had poor glycemic control with oral hypoglycemic agents, were enrolled at 10 hospitals in Beijing. Serum GA, HbA1c, fasting blood glucose (FBG), and C-peptide were assayed on Days 0, 14, 28, and 91 after treatment. RESULTS: Four hundred ninety-nine patients were enrolled. Mean FBG, GA and HbA1c decreased significantly in patients at Days 14, 28, and 91. In patients with improved glycemic control, the reduction of GA and HbA1c levels was 10.5±13.3% vs. 5.1±5.4% on Day 14, 16.0±13.4% vs. 9.0±7.0% on Day 28, and 18.0±16.7% vs. 18.3±9.4% on Day 91, respectively, compared with baseline values. Changes in GA on Day 14, 28 and 91 were all closely correlated with changes in HbA1c on Day 91. Change in GA on Day 14 was correlated with treatment effectiveness evaluated by HbA1c on Day 91. CONCLUSIONS: GA may be a useful marker for assessing glycemic control at an early stage of new diabetes treatment and assist in guiding adjustments to treatment and therapy.

Activation of ERK pathway is required for 15-HETE-induced angiogenesis in human umbilical vascular endothelial cells.

Angiogenesis plays a critical role in the progression of cardiovascular disease, retinal ischemia, or tumorigenesis. The imbalance of endothelial cell proliferation and apoptosis disturbs the establishment of the vasculogenesis, which is affected by several arachidonic acid metabolites. 15-Hydroxyeicosatetraenoic acid (15-HETE) is one of the metabolites. However, the underlying mechanisms of angiogenesis induced by 15-HETE in human umbilical vascular endothelial cells (HUVECs) are still poorly understood. Since extracellular signal-regulated kinase (ERK) is a critical regulator of cell proliferation, there may be a crosstalk between 15-HETE-regulating angiogenic process and ERK-proliferative effect in HUVECs. To test this hypothesis, we study the effect of 15-HETE on cell proliferation, angiogenesis, and apoptosis using cell viability measurement, cell cycle analysis, western blot, scratch-wound, tube formation assay, and nuclear morphology determination. We found that 15-HETE promoted HUVEC angiogenesis, which were mediated by ERK. Moreover, 15-HETE-induced proliferation and cell cycle transition from the G(0)/G(1) phase to the G(2)/M + S phase. All these effects were reversed after blocking ERK with PD98059 (an ERK inhibitor). In addition, HUVEC apoptosis was relieved by 15-HETE through the ERK pathway. Thus, ERK is necessary for the effects of 15-HETE in the regulation of HUVEC angiogenesis, which may be a novel potential target for the treatment of angiogenesis-related diseases.

Efficacy and safety of avandamet or uptitrated metformin treatment in patients with type 2 diabetes inadequately controlled with metformin alone: a multicenter, randomized, controlled trial.

BACKGROUND: At present, China has listed the compound tablet containing a fixed dose of rosiglitazone and metformin, Avandamet, which may improve patient compliance. The aim of this study was to evaluate the efficacy and safety of Avandamet or uptitrated metformin treatment in patients with type 2 diabetes inadequately controlled with metformin alone. METHODS: This study was a 48-week, multicenter, randomized, open-labeled, active-controlled trial. Patients with inadequate glycaemic control (glycated hemoglobin [HbA1c] 7.5-9.5%) receiving a stable dose of metformin (≥1500 mg) were recruited from 21 centers in China (from 19 November, 2009 to 15 March, 2011). The primary objective was to compare the proportion of patients who reached the target of HbA1c ≤7% between Avandamet and metformin treatment. RESULTS: At week 48, 83.33% of patients reached the target of HbA1c ≤7% in Avandamet treatment and 70.00% in uptitrated metformin treatment, with significantly difference between groups. The target of HbA1c ≤6.5% was reached in 66.03% of patients in Avandamet treatment and 46.88% in uptitrated metformin treatment. The target of fasting plasma glucose (FPG) ≤6.1 mmol/L was reached in 26.97% of patients in Avandamet treatment and 19.33% in uptitrated metformin treatment. The target of FPG ≤7.0 mmol/L was reached in 63.16% of patients in Avandamet treatment and 43.33% in uptitrated metformin treatment. Fasting insulin decreased 3.24 ± 0.98 µU/ml from baseline in Avandamet treatment and 0.72 ± 1.10 µU/ml in uptitrated metformin treatment. Overall adverse event (AE) rates and serious AE rates were similar between groups. Hypoglycaemia occurred rarely in both groups. CONCLUSIONS: Compared with uptitrated metformin, Avandamet treatment provided significant improvements in key parameters of glycemic control and was generally well tolerated. REGISTRATION NUMBER: ChiCTR-TRC-13003776.

Antitumor activity of adenoviral vector containing T42 and 4xT42 peptide gene through inducing apoptosis of tumor cells and suppressing angiogenesis.

The T42 peptide, generated from two active fragments of tumstatin, has been shown to have anti­tumor activity. The adenoviral vector is the most frequently used vector in research and clinical trials for gene therapy. In the present study, the anti­tumor activity of the T42 peptide and quadruple T42 (4xT42) peptide adenoviral vectors were elucidated for the first time, to the best of our knowledge. Human embryonic kidney 293 cells were infected with plasmid adenovirus (pAd)­enhanced green fluorescent protein (EGFP)­T42 or pAd­EGFP­4xT42 and the expression of the T42 and 4xT42 genes was confirmed by the identification of GFP expression and reverse transcription polymerase chain reaction experiments. The anti­cancer effects of pAd­EGFP­T42 and pAd­EGFP­4xT42 on breast cancer cells in vivo and in vitro were subsequently investigated. The results indicated that the packaging of the recombinant adenoviruses with the viral titer was successful, following purification at 5x109 plaque forming units/ml. The results also revealed that the recombinant adenoviruses promoted apoptosis in MCF­7 breast cancer cells and inhibited cancer growth. Through the analysis of caspase­3, B­cell lymphoma 2 (Bcl­2) and Bcl­2­associated X protein expression, it was demonstrated that the T42/4xT42 peptide may induce apoptosis via the mitochondrial pathway. In addition, mouse xenograft experiments confirmed that the T42 peptide inhibited tumor growth and reduced angiogenesis in vivo. In conclusion, the results of the present study indicated that the T42 and 4xT42 peptide genes, transfected by a recombinant adenovirus, may provide a potential novel strategy for the treatment of breast cancer.

Resiquimod and polyinosinic-polycytidylic acid formulation with aluminum hydroxide as an adjuvant for foot-and-mouth disease vaccine.

BACKGROUND: Toll-like receptor (TLR) agonists reportedly have potent antiviral and antitumor activities and may be a new kind of adjuvant for enhancing immune efficacy. Resiquimod (R848) is an imidazoquinoline compound with potent antiviral activity and functions through the TLR7/TLR8 MyD88-dependent signaling pathway. Polyinosinic-polycytidylic acid [poly(I:C)] is a synthetic analog of double-stranded RNA that induces the production of pro-inflammatory cytokines by the activation of NF-κB through TLR3. This study investigated the potential of R848 and poly(I:C) as an adjuvant 146S foot-and-mouth disease virus (FMDV) vaccine formulated with aluminum hydroxide (Al(OH)3). RESULTS: Antibody titers to FMDV and CD8+ T cells were markedly enhanced in mice immunized to 146S FMDV + Al(OH)3 + R848 + poly(I:C) compared with mice immunized to FMDV + ISA206. IFN-γ secretion substantially increased compared with IL-4 secretion by splenic T cells stimulated with FMDV antigens in vitro, suggesting that R848, poly(I:C), and with Al(OH)3 together biased the immune response toward a Th1-type direction. CONCLUSIONS: These results indicated that the R848 and poly(I:C) together with Al(OH)3 enhanced humoral and cellular immune responses to immunization with 146S FMDV antigens. Thus, this new vaccine formulation can be used for FMDV prevention.

Liposomes modified with P-aminophenyl-α-D-mannopyranoside: a carrier for targeting cerebral functional regions in mice.

Targeting of intracerebral functional regions has been limited by the inability to transport drugs across the blood-brain barrier (BBB) and by poor accumulation in these regions. To overcome these hurdles, liposomes modified with P-aminophenyl-α-d-mannopyranoside (MAN) were used as a fluorescent dye carrier through the BBB and used the specific distribution of liposomes (LIP) modified with MAN (MAN-LIP) to target various functional regions of the brain. An in vitro BBB model was established to evaluate the transendothelial ability of MAN-LIP, and liposomes uptake by C6 glioma cells was analyzed by flow cytometry and live cell imaging. Liposome targeting was evaluated using in vivo and ex vivo imaging. After MAN-LIP administration, the transendothelial ability and the delivery of fluorescent dye to the brain significantly increased. MAN-LIP concentrated in the cortex at 4 h, shifting distribution to the cerebellum and brainstem at 12 h. The fluorescence intensity in the hippocampus and pontine nuclei remained high and stable over a period of 12 h. The results demonstrate that MAN-LIP is able to enhance cellular uptake in vitro and also promotes penetration through the BBB and accumulation in the brain with a distinct spatio-temporal pattern.

Using increment of diversity to predict mitochondrial proteins of malaria parasite: integrating pseudo-amino acid composition and structural alphabet.

Due to the complexity of Plasmodium falciparum (PF) genome, predicting mitochondrial proteins of PF is more difficult than other species. In this study, using the n-peptide composition of reduced amino acid alphabet (RAAA) obtained from structural alphabet named Protein Blocks as feature parameter, the increment of diversity (ID) is firstly developed to predict mitochondrial proteins. By choosing the 1-peptide compositions on the N-terminal regions with 20 residues as the only input vector, the prediction performance achieves 86.86% accuracy with 0.69 Mathew's correlation coefficient (MCC) by the jackknife test. Moreover, by combining with the hydropathy distribution along protein sequence and several reduced amino acid alphabets, we achieved maximum MCC 0.82 with accuracy 92% in the jackknife test by using the developed ID model. When evaluating on an independent dataset our method performs better than existing methods. The results indicate that the ID is a simple and efficient prediction method for mitochondrial proteins of malaria parasite.

Alternative way to test the efficacy of swine FMD vaccines: measurement of pigs median infected dose (PID50) and regulation of live virus challenge dose.

Foot-and -mouth disease to pigs is serious recently around the world. "Vaccination prevention" is still an important policy. OIE specifies 10,000 TCID50(0.2 ml) of virulent virus for challenge test in pigs to test the potency of FMD vaccine by intradermal route inoculating the virus in the heel bulbs of one foot or by intramuscular route administering into one site of the neck behind the ear. Convenience and speediness are available in the process of potency test of commercial FMD vaccine. We selected the route of "administering into one site of the muscular part of the neck behind the ear" because of convenience and speediness. However, it was difficult to infect control pigs even up to 100,000TCID50, so we changed the challenged virus from cell-passaged strain to suckling mice-passaged one, measured its PID50 (pigs median infected dose) and defined the virus challenge dose as 1000PID50. Meanwhile, we arranged the number of control pigs from two to three for easy evaluation.

The efficacy of FMD vaccine reduced non-structural proteins with a mAb against 3B protein.

A monoclonal antibody, 3BIgG, against the prokaryotically expressed foot-and-mouth disease virus (FMDV) non-structural protein (NSP) 3B was obtained. The 3BIgG-sepharose conjugant (3BmAb-6BFF) was prepared by adding the purified 3BIgG into epoxy-activated sepharose 6BFF, incubating with the inactivated FMDV, and then removing the sepharose by centrifugation. The vaccine was made from the supernatant emulsified with oil-adjuvant ISA206. Ten guinea pigs, 26 pigs and six cattle were vaccinated, and a vaccination control group was included without treatment with 3BmAb-6BFF. After 28 days, 9/10 pigs challenged with FMDV were protected, this result was the same as the control group, indicating that the vaccine potency was not reduced after treatment with 3BmAb-6BFF. The other animals were vaccinated weekly for nine weeks, and serum samples were collected to detect 3ABC-antibody titers. The results showed that 3ABC-antibody production was delayed and the positive antibody rates were lower when vaccination was carried out using vaccines treated with 3BmAb-6BFF compared with untreated vaccines. The findings of this study suggest that it is possible to reduce NSPs using a mAb-sepharose conjugant in FMD vaccines without reducing their efficacy.

Prediction of subcellular localization of apoptosis protein using Chou's pseudo amino acid composition.

Apoptosis proteins play an essential role in regulating a balance between cell proliferation and death. The successful prediction of subcellular localization of apoptosis proteins directly from primary sequence is much benefited to understand programmed cell death and drug discovery. In this paper, by use of Chou's pseudo amino acid composition (PseAAC), a total of 317 apoptosis proteins are predicted by support vector machine (SVM). The jackknife cross-validation is applied to test predictive capability of proposed method. The predictive results show that overall prediction accuracy is 91.1% which is higher than previous methods. Furthermore, another dataset containing 98 apoptosis proteins is examined by proposed method. The overall predicted successful rate is 92.9%.

Multicenter clinical study on the efficacy and safety of inhalable insulin aerosol in the treatment of type 2 diabetes.

BACKGROUND: A new inhalable insulin aerosol (Inh-Ins) was developed in China. The aim of this multicenter clinical study was to evaluate the efficacy and safety of this new Inh-Ins as a treatment of type 2 diabetes. Regular porcine insulin (RI) was used as a control. METHODS: This study is a prospective, randomized, open-label, parallel-group multicenter clinical trial in which 253 qualified patients with type 2 diabetes received the insulin Glargine daily at bedtime plus either a pre-meal Inh-Ins or a pre-meal subcutaneous RI for 12 weeks. HbA1c, fasting plasma glucose (FPG), the 1-hour-postprandial blood glucose (1hPBG) and the 2-hour-postprandial blood glucose (2hPBG) were measured. Events were monitored for adverse effects. RESULTS: After 12 weeks, the HbA1c decreased significantly from baseline in both treatment groups, with no significant difference between the two regimens. In the Inh-Ins group, FPG, both 1hPBG and 2hPBG significantly declined from baseline after the 8th- and 12th-weeks of treatment. The reduced values of FPG or 1hPBG between the two groups showed a more significant hypoglycemic effect with the Inh-Ins than the RI. After 12 weeks, the pulmonary carbon monoxide diffusing capacity (DLco) was significantly lower in Inh-Ins group than in the RI. The main side effects of Inh-Ins were coughing, excessive sputum, and hypoglycemia. CONCLUSIONS: Inh-Ins was effective in decreasing HbA1c like the RI. It was better in lowering the FPG and the 1hPBG than the RI. Its main side effects were coughing, excessive sputum, and hypoglycemia. Also, Inh-Ins slightly impaired DLco.

Prediction of apoptosis protein subcellular location using improved hybrid approach and pseudo-amino acid composition.

Apoptosis proteins are very important for understanding the mechanism of programmed cell death. The apoptosis protein localization can provide valuable information about its molecular function. The prediction of localization of an apoptosis protein is a challenging task. In our previous work we proposed an increment of diversity (ID) method using protein sequence information for this prediction task. In this work, based on the concept of Chou's pseudo-amino acid composition [Chou, K.C., 2001. Prediction of protein cellular attributes using pseudo-amino acid composition. Proteins: Struct. Funct. Genet. (Erratum: Chou, K.C., 2001, vol. 44, 60) 43, 246-255, Chou, K.C., 2005. Using amphiphilic pseudo-amino acid composition to predict enzyme subfamily classes. Bioinformatics 21, 10-19], a different pseudo-amino acid composition by using the hydropathy distribution information is introduced. A novel ID_SVM algorithm combined ID with support vector machine (SVM) is proposed. This method is applied to three data sets (317 apoptosis proteins, 225 apoptosis proteins and 98 apoptosis proteins). The higher predictive success rates than the previous algorithms are obtained by the jackknife tests.