The Open Biochemistry Journal[JOURNAL]
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130 papers
Serum copper, zinc and lipid peroxidation in pregnant women with preeclampsia in gorgan.
Rafeeinia A, Tabandeh A, Khajeniazi S … +1 more , Marjani AJ
Open Biochem J · 2014 · PMID 25400710 · Full text
The aim of study was to assay serum copper, zinc and lipid peroxidation levels in pregnant women with and without preeclampsia. There were significant differences between systolic, diastolic blood pressures and copper, C...
The aim of study was to assay serum copper, zinc and lipid peroxidation levels in pregnant women with and without preeclampsia. There were significant differences between systolic, diastolic blood pressures and copper, Cu/Zn ratio and malondialdehyde among two groups. There were significant differences in weight, pre-pregnancy body mass index, systolic, diastolic blood pressures and copper, Cu/Zn ratio and malondialdehyde levels when compared to healthy pregnant women with mild and severe preeclampsia patients. A positive correlation was observed between systolic and diastolic blood pressure and copper, malondialdehyde and Cu/Zn ratio. Copper and malondialdehyde may play a role in the pathophysiology of preeclampsia.
Certain Diet and Lifestyle May Contribute to Islet β-cells Protection in Type-2 Diabetes via the Modulation of Cellular PI3K/AKT Pathway.
Kitagishi Y, Nakanishi A, Minami A … +7 more , Asai Y, Yasui M, Iwaizako A, Suzuki M, Ono Y, Ogura Y, Matsuda S
Open Biochem J · 2014 · PMID 25400709 · Full text
PI3K/AKT pathway has been shown to play a pivotal role on islet β-cell protection, enhancing β-cell survival by stimulating cell proliferation and inhibiting cell apoptosis. Accordingly, this pathway appears to be crucia...
PI3K/AKT pathway has been shown to play a pivotal role on islet β-cell protection, enhancing β-cell survival by stimulating cell proliferation and inhibiting cell apoptosis. Accordingly, this pathway appears to be crucial in type-2 diabetes. Understanding the regulations of this pathway may provide a better efficacy of new therapeutic approaches. In this review, we summarize advances on the involvement of the PI3K/AKT pathway in hypothetical intra-cellular signaling of islet β-cells. As recent findings may show the nutritional regulation of the survival pathway in the islet β-cells through activation of the PI3K/AKT pathway, we also review studies on the features of several diets, correlated lifestyle, and its signaling pathway involved in type-2 diabetes. The molecular mechanisms contributing to the disease are the subject of considerable investigation, as a better understanding of the pathogenesis will lead to novel therapies against a condition of the disease.
NO Metabolites Levels in Human Red Blood Cells are Affected by Palytoxin, an Inhibitor of Na(+)/K(+)-ATPase Pump.
Carelli-Alinovi C, Tellone E, Russo AM … +5 more , Ficarra S, Pirolli D, Galtieri A, Giardina B, Misiti F
Open Biochem J · 2014 · PMID 25246985 · Full text
Palytoxin (PTX), a marine toxin, represents an increasing hazard for human health. Despite its high toxicity for biological systems, the mechanisms triggered by PTX, are not well understood. The high affinity of PTX for...
Palytoxin (PTX), a marine toxin, represents an increasing hazard for human health. Despite its high toxicity for biological systems, the mechanisms triggered by PTX, are not well understood. The high affinity of PTX for erythrocyte Na(+)/K(+)-ATPase pump is largely known, and it indicates PTX as a sensitive tool to characterize the signal transducer role for Na(+)/K(+)-ATPase pump. Previously, it has been reported that in red blood cells (RBC), probably via a signal transduction generated by the formation of a PTX-Na(+)/K(+)-ATPase complex, PTX alters band 3 functions and glucose metabolism. The present study addresses the question of which other signaling pathways are regulated by Na(+)/K(+)-ATPase in RBC. Here it has been evidenced that PTX following its interaction with Na(+)/K(+)-ATPase pump, alters RBC morphology and this event is correlated to decreases by 30% in nitrites and nitrates levels, known as markers of plasma membrane eNOS activity. Orthovanadate (OV), an antagonist of PTX binding to Na(+)/K(+)-ATPase pump, was able to reverse the effects elicited by PTX. Finally, current investigation firstly suggests that Na(+)/K(+)-ATPase pump, following its interaction with PTX, triggers a signal transduction involved in NO metabolism regulation.
The CCA-end of P-tRNA Contacts Both the Human RPL36AL and the A-site Bound Translation Termination Factor eRF1 at the Peptidyl Transferase Center of the Human 80S Ribosome.
Hountondji C, Bulygin K, Créchet JB … +7 more , Woisard A, Tuffery P, Nakayama J, Frolova L, Nierhaus KH, Karpova G, Baouz S
Open Biochem J · 2014 · PMID 25191528 · Full text
We have demonstrated previously that the E-site specific protein RPL36AL present in human ribosomes can be crosslinked with the CCA-end of a P-tRNA in situ. Here we report the following: (i) We modeled RPL36AL into the s...
We have demonstrated previously that the E-site specific protein RPL36AL present in human ribosomes can be crosslinked with the CCA-end of a P-tRNA in situ. Here we report the following: (i) We modeled RPL36AL into the structure of the archaeal ortholog RPL44E extracted from the known X-ray structure of the 50S subunit of Haloarcula marismortui. Superimposing the obtained RPL36AL structure with that of P/E tRNA observed in eukaryotic 80S ribosomes suggested that RPL36AL might in addition to its CCA neighbourhood interact with the inner site of the tRNA elbow similar to an interaction pattern known from tRNA•synthetase pairs. (ii) Accordingly, we detected that the isolated recombinant protein RPL36AL can form a tight binary complex with deacylated tRNA, and even tRNA fragments truncated at their CCA end showed a high affinity in the nanomolar range supporting a strong interaction outside the CCA end. (iii) We constructed programmed 80S complexes containing the termination factor eRF1 (stop codon UAA at the A-site) and a 2',3'-dialdehyde tRNA (tRNAox) analog at the P-site. Surprisingly, we observed a crosslinked ternary complex containing the tRNA, eRF1 and RPL36AL crosslinked both to the aldehyde groups of tRNAox at the 2'- and 3'-positions of the ultimate A. We also demonstrated that, upon binding to the ribosomal A-site, eRF1 induces an alternative conformation of the ribosome and/or the tRNA, leading to a novel crosslink of tRNAox to another large-subunit ribosomal protein (namely L37) rather than to RPL36AL, both ribosomal proteins being labeled in a mutually exclusive fashion. Since the human 80S ribosome in complex with P-site bound tRNAox and A-site bound eRF1 corresponds to the post-termination state of the ribosome, the results represent the first biochemical evidence for the positioning of the CCA-arm of the P-tRNA in close proximity to both RPL36AL and eRF1 at the end of the translation process.
Acute Phase Response: Implication in ST-segment Elevation Myocardial Infarction.
Eren E, Ellidag HY, Yılmaz A … +2 more , Aydın O, Yılmaz N
Open Biochem J · 2014 · PMID 24894970 · Full text
We aimed to investigate the relation between serum inflammatory markers, 25OHvit-D3 and oxidative stress markers, namely paraoxonase1-arylesterase (PON1-ARE), total antioxidant status (TAS) and total oxidant status (TOS)...
We aimed to investigate the relation between serum inflammatory markers, 25OHvit-D3 and oxidative stress markers, namely paraoxonase1-arylesterase (PON1-ARE), total antioxidant status (TAS) and total oxidant status (TOS) in 30 male patients with ST-elevation myocardial infarction(STEMI) . There was negative correlation between tumor necrosis factor alpha and ARE; positive correlations between serum amyloid A(SAA) and oxidative stress index, SAA and TOS, 25OHvit-D3 and ARE. There was no statistically significant correlation between inflammation makers, oxidative stress markers and Gensini score. The main finding of our study was the tendency of inflammation markers, and oxidative stress markers, to change in relatively clear opposite directions in STEMI.
A Novel Approach to Simulate a Charge Transfer in DNA Repair by an Anacystis nidulans Photolyase.
Dushanov EB, Kholmurodov KhT
Open Biochem J · 2014 · PMID 24772194 · Full text
An Anacystis nidulans photolyase enzyme containing two chromophore cofactors was simulated for a photoreaction DNA repairing process via molecular dynamics (MD) method. A novel approach has been introduced for the electr...
An Anacystis nidulans photolyase enzyme containing two chromophore cofactors was simulated for a photoreaction DNA repairing process via molecular dynamics (MD) method. A novel approach has been introduced for the electron transfer between the FAD (flavin adenine dinucleotide; flavin) molecule and CPD (cyclobutane pyrimidine dimer). This approach involves four simulation stages with different charges for the FAD and CPD fragments and a role of a charged state of the active cofactor was qualified during the MD modeling. Observations show that flavin has actively participated in a charge transfer process, thereby involving the conformational changes of the DNA and CPD substrate fragment. The DNA conformation behavior has shown to correlate with the electron transfer from flavin to CPD. This is manifested on the similarities of the DNA repairing process by excision repair of the UV photoproducts.
Study on Certain Biomarkers of Inflammation in Psoriasis Through "OMICS" Platforms.
Rodríguez-Cerdeira C, Molares-Vila A, Sánchez-Blanco E … +1 more , Sánchez-Blanco B
Open Biochem J · 2014 · PMID 24688608 · Full text
BACKGROUND: In recent years, research on psoriasis has focused on the identification of biomarkers for the diagnosis, pathogenesis, prognosis, or therapeutic response of the disease. These studies could provide insights...
BACKGROUND: In recent years, research on psoriasis has focused on the identification of biomarkers for the diagnosis, pathogenesis, prognosis, or therapeutic response of the disease. These studies could provide insights into the susceptibility and natural history of psoriasis. The identification of biomarkers related to comorbidities in psoriasis, such as arthritis, cardiovascular disease, and the metabolic syndrome, is of special clinical interest. MATERIALS AND METHODS: We performed an extensive review on psoriasis biomarkers, including cytokine and growth factors, in the literature published between 1997 and 2013, including cross-references of any retrieved articles. We also included some data from our own studies. RESULTS: This review presents current knowledge of soluble biomarkers in psoriasis, including cytokines, chemokines, proangiogenic mediators, growth factors, antimicrobial proteins, neuropeptides, and oxidative stress markers. CONCLUSION: In conclusion, a number of studies have been conducted with the aim of establishing soluble biomarkers for psoriasis. Most of the biomarkers that have been studied do not meet the criteria for a clinically useful biomarker. Further work is needed to establish a role for soluble biomarkers in the diagnosis and treatment of psoriasis, with a special focus on biomarkers for psoriasis comorbidities, such as arthritis, cardiovascular disease, and the metabolic syndrome.
Effect of Target Length on Specificity and Sensitivity of Oligonucleotide Microarrays: A Comparison between Dendrimer and Modified PCR based Labelling Methods.
Gibriel A
Open Biochem J · 2014 · PMID 24551024 · Full text
DNA microarrays are widely used as end point detectors for gene expression analysis. Several methods have been developed for target labelling to enable quantification but without taking target length into consideration....
DNA microarrays are widely used as end point detectors for gene expression analysis. Several methods have been developed for target labelling to enable quantification but without taking target length into consideration. Here we highlight the importance of choosing the optimum target length that would ensure specificity without compromising sensitivity of the assay. For this, eight plasmids that are identical to each other except for a closely related 23 bp unique reporter (UR) sequence were used to examine the hybridization efficiency for these URs. Targets of various lengths were generated and labelled as follows: full length and 330 bases transcripts using a dendrimer labelling method, 120 bp amplicons by the modified PCR end labelling method and synthetic labelled targets of 33 bases. This report also shows the advantages of using the modified PCR method over other labelling methods in generating labelled amplicons of the desired lengths to maximize hybridization efficiency.
Unique Photobleaching Phenomena of the Twin-Arginine Translocase Respiratory Enzyme Chaperone DmsD.
Rivardo F, Leach TG, Chan CS … +4 more , Winstone TM, Ladner CL, Sarfo KJ, Turner RJ
Open Biochem J · 2014 · PMID 24497893 · Full text
DmsD is a chaperone of the redox enzyme maturation protein family specifically required for biogenesis of DMSO reductase in Escherichia coli. It exists in multiple folding forms, all of which are capable of binding its k...
DmsD is a chaperone of the redox enzyme maturation protein family specifically required for biogenesis of DMSO reductase in Escherichia coli. It exists in multiple folding forms, all of which are capable of binding its known substrate, the twin-arginine leader sequence of the DmsA catalytic subunit. It is important for maturation of the reductase and targeting to the cytoplasmic membrane for translocation. Here, we demonstrate that DmsD exhibits an irreversible photobleaching phenomenon upon 280 nm excitation irradiation. The phenomenon is due to quenching of the tryptophan residues in DmsD and is dependent on its folding and conformation. We also show that a tryptophan residue involved in DmsA signal peptide binding (W87) is important for photobleaching of DmsD. Mutation of W87, or binding of the DmsA twin-arginine signal peptide to DmsD in the pocket that includes W72, W80, and W91 significantly affects the degree of photobleaching. This study highlights the advantage of a photobleaching phenomenon to study protein folding and conformation changes within a protein that was once considered unusable in fluorescence spectroscopy.
Biophysical mechanisms of the neutralization of endotoxins by lipopolyamines.
Sil D, Heinbockel L, Kaconis Y … +5 more , Rössle M, Garidel P, Gutsmann T, David SA, Brandenburg K
Open Biochem J · 2013 · PMID 24133550 · Full text
Endotoxins (lipopolysaccharides, LPS) are one of the strongest immunostimulators in nature, responsible for beneficial effects at low, and pathophysiological effects at high concentrations, the latter frequently leading...
Endotoxins (lipopolysaccharides, LPS) are one of the strongest immunostimulators in nature, responsible for beneficial effects at low, and pathophysiological effects at high concentrations, the latter frequently leading to sepsis and septic shock associated with high mortality in critical care settings. There are no drugs specifically targeting the pathophysiology of sepsis, and new therapeutic agents are therefore urgently needed. The lipopolyamines are a novel class of small molecules designed to sequester and neutralize LPS. To understand the mechanisms underlying the binding and neutralization of LPS toxicity, we have performed detailed biophysical analyses of the interactions of LPS with candidate lipopolyamines which differ in their potencies of LPS neutralization. We examined gel-to-liquid crystalline phase behavior of LPS and of its supramolecular aggregate structures in the absence and presence of lipopolyamines, the ability of such compounds to incorporate into different membrane systems, and the thermodynamics of the LPS:lipopolyamine binding. We have found that the mechanisms which govern the inactivation process of LPS obey similar rules as found for other active endotoxin neutralizers such as certain antimicrobial peptides.
Characterization of the Stoichiometry of HMGA1/DNA Complexes.
Watanabe M, Ni S, Lindenberger AL … +3 more , Cho J, Tinch SL, Kennedy MA
Open Biochem J · 2013 · PMID 24062859 · Full text
High-mobility group A1 (HMGA1) non-histone chromatin architectural transcription factors regulate gene expression, embryogenesis, cell differentiation, and adaptive immune responses by binding DNA and other transcription...
High-mobility group A1 (HMGA1) non-histone chromatin architectural transcription factors regulate gene expression, embryogenesis, cell differentiation, and adaptive immune responses by binding DNA and other transcription factors. HMGA1 has also been shown to be highly over-expressed in many human cancers and is considered to be a valuable cancer biomarker. Elevated HMGA1 expression levels also make cancer cells resistant to chemotherapy. Here, HMGA1/DNA complex formation was investigated using electrophoretic mobility shift assays (EMSA). Collectively, the EMSA results indicated that full length HMGA1 mixed with DNA containing three AT-hook binding sites formed four distinct HMGA1/DNA complexes ranging in stoichiometry from 1:2 to 3:1 in HMGA1:DNA ratio. The data indicated that the distribution of complexes with different HMGA1 to DNA stoichiometries depended on the molar ratio of HMGA1 to DNA in solution, which could have significant biological implications given that HMGA1 is highly over-expressed in human cancer cells. The two naturally occurring isoforms of HMGA1, HMGA1a and HMGA1b, the latter containing an 11 amino acid deletion between the first and second AT-hooks, were observed to have slightly different DNA binding profiles. Finally, HMGA1 binding affinity to DNA was found to be influenced by the DNA A:T segment sequence context, with higher specificity be observed in HMGA1 binding to TnAn segments, which have two local minor groove minima on either side of the TpA step, compared to An:Tn segments, which have a single minor groove minimum at the 3' end of the An run, implying AT-hook binding favors narrow minor groove structure.
Phosphorylation of Tip60 Tyrosine 327 by Abl Kinase Inhibits HAT Activity through Association with FE65.
Shin SH, Kang SS
Open Biochem J · 2013 · PMID 24044023 · Full text
The transfer of acetyl groups from acetyl coenzyme A to the ε amino group of internal lysine residues is catalyzed by Tip60, which is in the MYST family of nuclear histone acetyltransferases (HATs). The tyrosine phosphor...
The transfer of acetyl groups from acetyl coenzyme A to the ε amino group of internal lysine residues is catalyzed by Tip60, which is in the MYST family of nuclear histone acetyltransferases (HATs). The tyrosine phosphorylation of Tip60 seems to be a unique modification. We present evidence that Tip60 is modified on tyrosine 327 by Abl kinase. We show that this causes functional changes in HAT activity and the subcellular localization of TIP60, which forms a complex with Abl kinase. The Tip60 mutation Y327F abolished tyrosine phosphorylation, reduced the inhibition of Tip60 HAT activity, and caused G0-G1 arrest and association with FE65. Thus, our findings for the first time suggested a novel regulation mechanism of Tip60. Regulation was through phosphorylation of tyrosine 327 by Abl tyrosine kinase and depended on environmental conditions, suggesting that the tyrosine residue of Tip60 is important for the activation process.
Effects of redox state on the efficient uptake of cell permeable Peptide in Mammalian cells.
Squires S, Christians E, Riedel M … +4 more , Timothy D, Rodesch CK, Marvin J, Benjamin I
Open Biochem J · 2013 · PMID 23919090 · Full text
We investigated whether a cell-penetrating peptide linked via a disulfide bond to a fluorophore-labeled cargo peptide can be used to interrogate changes in cellular redox state. A fluorescence resonance energy transfer (...
We investigated whether a cell-penetrating peptide linked via a disulfide bond to a fluorophore-labeled cargo peptide can be used to interrogate changes in cellular redox state. A fluorescence resonance energy transfer (FRET) pair was constructed so that the cargo peptide was labeled with fluorescein amidite (FAM) and the cell-penetrating peptide was attached to a quencher. Incubation of cells in culture with the FRET construct was visualized using live-cell, time-lapse imaging, which demonstrated earlier cellular uptake of the construct when cells were treated with the reducing agent n-acetylcysteine (NAC). The FRET peptide construct was easily detected in cells cultured in 96-well plates using a plate-reader. Treatment of cells with various classes of reducing or oxidizing agents resulted in an increase or decrease in FAM fluorescence, respectively. Changes in FAM fluorescence correlated significantly with redox-sensitive green fluorescent protein ratios in cells treated with hydrogen peroxide but not NAC. Detection of relative changes in cellular redox state was enhanced by the fact that uptake of the cell-penetrating peptide occurred more quickly in relatively reduced compared with oxidized cells. We conclude that cell-penetrating peptides coupled via disulfide bonds to detectable cargo is a novel and specific approach for assessment of relative changes in cellular thiol redox state.
Activation Energy Calculations for Formamide-TiO2 and Formamide-Pt Interactions in the Presence of Water.
Dushanov E, Kholmurodov Kh, Yasuoka K
Open Biochem J · 2013 · PMID 23802018 · Full text
Formamide contains the four elements (C, H, O, and N) most required for life and it is attractive as a potential prebiotic starting material for nucleobase synthesis. In the presence of catalysts (for example, TiO2) and...
Formamide contains the four elements (C, H, O, and N) most required for life and it is attractive as a potential prebiotic starting material for nucleobase synthesis. In the presence of catalysts (for example, TiO2) and with moderate heating, formamide can pass surface energy barriers, yielding a complete set of nucleic bases and acyclonucleosides, and favoring both phosphorylations and transphosphorylations necessary for life. In the reaction mechanism, interaction with water seems to be an essential factor for the formamide molecule to function. In this paper, a formamide-water solution on a TiO$_2$ (anatase) surface is simulated using the molecular dynamics method, and activation energy calculations are performed for the temperature range of T = 250 K to T = 400 K. A correlation is established between the diffusion and density profiles for the formamide and water molecules on an anatase surface. Also, the calculated activation energies of the formamide-water-anatase and formamide-water-platinum systems are compared. A comparative analysis is performed of the behavior of formamide-water and ethanol-water interaction on the same (anatase and platinum) surfaces.
Different redox response elicited by naturally occurring antioxidants in human endothelial cells.
Giordo R, Cossu A, Pasciu V … +3 more , Hoa PT, Posadino AM, Pintus G
Open Biochem J · 2013 · PMID 23730364 · Full text
Evidences that higher natural antioxidant (NA) intake provides protection against cardiovascular disease (CVD) are contradictory. Oxidative-induced endothelial cells (ECs) injury is the key step in the onset and progress...
Evidences that higher natural antioxidant (NA) intake provides protection against cardiovascular disease (CVD) are contradictory. Oxidative-induced endothelial cells (ECs) injury is the key step in the onset and progression of CVD and for this reason the cellular responses resulting from NA interaction with ECs are actively investigated. This study was designed to investigate the direct impact of different naturally occurring antioxidants on the intracellular ROS levels in cultured human ECs. NA-induced redox changes, in terms of modulation of the intracellular ROS levels, were assessed by using the ROS fluorescent probe 2',7'-dichlorodihydrofluorescein diacetate (H2DCF-DA). While caffeic and caftaric acid exerted an anti-oxidant effect, both coumaric acid and resveratrol were pro-oxidant. Anti- and pro-oxidant effects of the tested compounds were concentration dependent, showing the induction or the tendency to promote a pro-oxidant outcome with increasing concentrations. Interestingly, the anti- and pro-oxidant behavior of chlorogenic and ferulic acid was dependent on the basal intracellular redox state. Our data indicate that naturally occurring antioxidants are able to induce a rapid modification of the intracellular ROS levels in human ECs, which is dependent on both the applied concentration and the intracellular redox state.
Nitric oxide and its metabolites in the critical phase of illness: rapid biomarkers in the making.
Mian AI, Aranke M, Bryan NS
Open Biochem J · 2013 · PMID 23539501 · Full text
The potential of nitric oxide (NO) as a rapid assay biomarker, one that could provide a quantum leap in acute care, remains largely untapped. NO plays a crucial role as bronchodilator, vasodilator and inflammatory mediat...
The potential of nitric oxide (NO) as a rapid assay biomarker, one that could provide a quantum leap in acute care, remains largely untapped. NO plays a crucial role as bronchodilator, vasodilator and inflammatory mediator. The main objective of this review is to demonstrate how NO is a molecule of heavy interest in various acute disease states along the emergency department and critical care spectrum: respiratory infections, central nervous system infections, asthma, acute kidney injury, sepsis, septic shock, and myocardial ischemia, to name just a few. We discuss how NO and its oxidative metabolites, nitrite and nitrate, are readily detectable in several body compartments and fluids, and as such they are associated with many of the pathophysiological processes mentioned above. With methods such as high performance liquid chromatography and chemiluminescence these entities are relatively easy and inexpensive to analyze. Emphasis is placed on diagnostic rapidity, as this relates directly to quality of care in acute care situations. Further, a rationale is provided for more bench, translational and clinical research in the field of NO biomarkers for such settings. Developing standard protocols for the aforementioned disease states, centered on concentrations of NO and its metabolites, can prove to revolutionize diagnostics and prognostication along a spectrum of clinical care. We present a strong case for developing these biomarkers more as point-of-care assays with potential of color gradient test strips for rapid screening of disease entities in acute care and beyond. This will be relevant to global health.
Comparison of Glycemic Excursion in Patients with New Onset Type 2 Diabetes Mellitus before and after Treatment with Repaglinide.
Hezarkhani S, Bonakdaran S, Rajabian R … +2 more , Shahini N, Marjani A
Open Biochem J · 2013 · PMID 23526382 · Full text
Due to industrialization and sedentary life, incidence of type 2 diabetes (DM2) is increasing seriously. Repaglinide is a glucose reducing agent that predominantly reduces post-prandial glucose. Continuous glucose monito...
Due to industrialization and sedentary life, incidence of type 2 diabetes (DM2) is increasing seriously. Repaglinide is a glucose reducing agent that predominantly reduces post-prandial glucose. Continuous glucose monitoring system (CGMS) monitors blood glucose excursions over a 3-day period. CGMS can be used as a therapeutic and diagnostic instrument in diabetics. There are not enough studies about using CGMS in DM2. The aim of this study was to determine the blood glucose excursions in patients with new onset of DM2. 10 patients with new onset of DM2 were entered to this study. As the first therapeutic management, patients received diabetic diet and moderate exercise for 3-weeks, if they did not achieve blood glucose goal (Fasting blood glucoser (FBG) <120mg/dl, 2-hour postprandial blood glucose (2hpp) <180mg/dl), were considered to undergo 3-days CGMS at baseline and after 4-weeks on Repaglinide (0.5mg three times before meals). Mean excursions of blood glucose were not different at the onset and at the end of treatment (6±4.05 VS 7.6±5.2 episodes, P=0.49). There were also no significant differences between mean duration of hypoglycemic episodes (zero VS 5.1±14.1 hours, P =0.28) and hyperglycemic episodes before and after therapy (7.6±5.2 VS 5.7±4.1, P=0.42), but mean hyperglycemia duration was significantly reduced at the end of therapy (21±26.17 VS 57.7±35.3, P=0.001). Patients experienced a mean of 0.3±0.67 episodes of hypoglycemia after therapy showed no significant difference before it (P =0.19). Mean FBG (with CGMS) was significantly lower after therapy than before it (142.9±54.31 VS 222.9±82.6, P <0.001). This study showed the usefulness of CGMS not only as a diagnostic but also as an educational and therapeutic tool that in combination with Repaglinide (with the lowest effective dose and duration) can significantly reduce FBG and glycemic excursions in DM2 patients and hypoglycemic events are low.
Age related metabolic syndrome among hemodialysis patients in gorgan, iran.
Marjani A, Moujerloo M, Hezarkhani S
Open Biochem J · 2013 · PMID 23459155 · Full text
People with metabolic syndrome are at high risk for developing cardiovascular disease. The present study aimed to determine the age related metabolic syndrome of hemodialysis patients. The biochemical parameters and demo...
People with metabolic syndrome are at high risk for developing cardiovascular disease. The present study aimed to determine the age related metabolic syndrome of hemodialysis patients. The biochemical parameters and demographic information were registered. The prevalence of metabolic syndrome was significantly high in ages 50-59 and 60-69 years in hemodialysis patients when compared with other age groups (P< 0.05). There was elevated frequency of metabolic syndrome from age 50-59 and 40-49 years in male and female hemodialysis patients, respectively. The frequency of metabolic syndrome in female subjects (65.27%) was higher than male (47.14%, P<0.05). The prevalence of metabolic syndrome was high in ages 50-59 years in males and females. There was a significant difference in hemodialysis patients with metabolic syndrome in ages 50-59 years in males and from ages 40-49, 50-59 and 60-69 years in females (P< 0.05). Our results show that 25.71%, 18.57% and 2.86% males and 36.11%, 20.83% and 8.33% females had three, four and five criteria for metabolic syndrome, respectively. The results of this study showed that females patients were more affected than males. This may depended on the specific lifestyle alterations among females and males patients in this area.
The involvement of xanthohumol in the expression of annexin in human malignant glioblastoma cells.
Festa M, Caputo M, Cipolla C … +4 more , D'Acunto C, Rossi A, Tecce M, Capasso A
Open Biochem J · 2013 · PMID 23407460 · Full text
Glioblastoma multiforme (GBM) is the most common malignant and resistant tumor of the central nervous system in humans and new therapeutic strategies are urgently required. Recently, we have shown that the potential chem...
Glioblastoma multiforme (GBM) is the most common malignant and resistant tumor of the central nervous system in humans and new therapeutic strategies are urgently required. Recently, we have shown that the potential chemotherapeutic polyphenol xanthohumol (XH), isolated from Humulus Lupulus, induces apoptosis of human T98G glioblastoma cells by increasing reactive oxygen species and activating MAPK pathways. Then we have found, by western blotting and microscopic analysis, that XH up-regulates cytosolic levels of ANXA1 and induces translocation of the protein on the cell membrane of T98G cells in a time-dependent manner with significant effects observed after 24 h. On the basis of the above evidence, the aim of this work was to investigate the role of intracellular and cell membrane localized ANXA1 in GBM cells. RT-PCR analysis has shown that XH up-regulates mRNA levels of ANXA1 after 16 h treatment. To demonstrate the involvement of ANXA1 in apoptosis of GBM cells we down-regulated ANXA1 expression with small interfering RNA (siRNA) and then analysed apoptosis in the presence and absence of apoptotic stimuli. Importantly, apoptosis induced by XH was reduced in siRNA-ANXA1 transfected cells where western blot analysis shows a significant reduction of ANXA1 protein levels. To investigate the role of ANXA1 expression on the cell membrane of T98G cells as potential "eat-me" signal we studied phagocytosis of apoptotic cells by human macrophages. We incubated apoptotic T98G cells with human blood monocyte derived macrophages (M=). After co-incubation period we analysed the percentage of M= phagocytosing the apoptotic cells by cytofluorimetric FACS analysis and by confocal microscopy. Our results show that XH induces phagocytosis of apoptotic T98G cells by human M= in a concentration-effect manner, a processes that is dependent on caspase mediated apoptosis. ANXA1 acts as an "eat-me" signal on the cell membrane of T98G cells, and interestingly, apoptotic siRNA-ANXA1 transfected cells are not completely ingested by M=. These results were confirmed by incubating apoptotic cells with a neutralizing anti-ANXA1 antiboby and ANXA1 membrane depletion by EDTA washing. ANXA1 was also detected in supernatants of apoptotic cells and the incubation of enriched supernatants enhanced the percentage of phagocytosis by M=. These results demonstrated that ANXA1 is involved both in the apoptosis and phagocytosis of glioblastoma cells. This study shows a possible role of ANXA1 in maintenance of brain homeostasis and may lead to novel therapeutic approaches for neuro-inflammatory diseases and chemotherapy targets in the treatment of glioblastoma multiforme.
The Stimulatory Mechanism of Hepatitis C Virus NS5A Protein on the NS5B Catalyzed Replication Reaction In Vitro.
Quezada EM, Kane CM
Open Biochem J · 2013 · PMID 23407362 · Full text
The Hepatitis C Virus RNA dependent RNA polymerase, NS5B, is stimulated by the NS5A protein in vitro. To explore this stimulatory mechanism, we compared the activity of a mutant of NS5B containing a deletion of the β-loo...
The Hepatitis C Virus RNA dependent RNA polymerase, NS5B, is stimulated by the NS5A protein in vitro. To explore this stimulatory mechanism, we compared the activity of a mutant of NS5B containing a deletion of the β-loop region with that of the full length NS5B in response to NS5A. While the NS5A protein does stimulate full length NS5B, NS5A does not stimulate the NS5B deletion mutant during either replication initiation or elongation. This result suggests that the activation mechanism might involve a NS5A-mediated conformational change of the β-loop of NS5B. Such a conformational change would be predicted to prevent steric clash of the RNA template and newly synthesized RNA product. Consistent with this hypothesis, RNA binding is enhanced when the full length NS5B and NS5A are incubated with RNA, but RNA binding is unchanged with incubation of NS5A and the NS5B β-loop deletion mutant.
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