• Title/Summary/Keyword: molecular pathogenesis

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Bcl-2 Gene Expression in Human Breast Cancers in Iran

  • Rostamizadeh, Leila;Fakhrjou, Ashraf;Montazeri, Vahid;Estiar, Mehrdad Asghari;Naghavi-Behzad, Mohammad;Hosseini, Somayyeh;Sakhinia, Masoud;Sakhinia, Ebrahim
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.7
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    • pp.4209-4214
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    • 2013
  • Background: Breast cancer is among the five most common cancers and ranks first among cancers diagnosed in Iranian women. Screening and treatment of this disease with molecular methods, especially regarding high incidences at early age and advanced stage, is essential. Several genes with altered expression have been identified by cDNA microarray studies in breast cancer, with the Bcl-2 gene indicated as a likely candidate. In this study, we studied Bcl-2 gene expression levels in parallel tumor and non-tumor breast tissues. Materials and Methods: Forty samples including 21 tumor, 16 non tumor (marginal) and 3 benign breast tissues which were all pathologically diagnosed, were subjected to RNA extraction and polyA RT-PCR with the expression level of Bcl-2 quantified using real-time PCR. Results: There is higher expression levels of the Bcl-2 gene in tumor samples compared with marginal samples, but not attaining significance(p>0.05). Bcl-2 expression in 14 (66.7%) of the cases of tumor samples and 9 (56.3%) cases of the marginal samples were positive. Comparison of the expression of the Bcl-2 gene in histological grade showed that a high expression of Bcl-2 was associated with a high histological grade (p<0.41). Conclusions: Our data suggests that dysregulated Bcl-2 gene expression is potentially involved in the pathogenesis of breast cancer. Using gene expression analysis may significantly improve our ability for screening cancer patients and will prove a powerful tool in the diagnosis and prognostic evaluation of the disease whilst aiding the cooperative group trials in the Bcl-2 based therapy project.

The Experimental Stydy on the Anti-Allergic Rhinitis Effects of the Sochungryong-tang (小靑龍湯이 알레르기 鼻炎에 미치는 效果에 대한 實驗的 硏究)

  • Park Ju-ho;Sim Sung-yong;Um Yu-sik;Nam Hae-jeong;Kim Kyung-jun
    • The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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    • v.17 no.1
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    • pp.55-65
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    • 2004
  • Allergic rhinitis is an inflammation of the nasal mucosa which is triggered by an allergic reaction. When exposed to certain allergens, the IgE covered mast cells degranulate releasing inflammatory mediators and cytokines which results in a local inflammatory reaction. In many recent studies, molecular biological methods have been used to investigate the role of cytokines in pathogenesis and new therapeutic targets of allergic rhinitis. This experimental study was done to research effects of Sochungryong-tang. We have studied effect of mice on OVA-induced production of IL-4, IL-5, IFN-${\gamma}$ by murine splenocytes and effect of OVA-induced total IgE and OVA-specific IgE. The results were as follows; 1. In IL-4 study, Sochungryong-tang treated group was proved significant inhibitory effect(p〈0.005). 2. In IL-5 study, Sochungryong-tang treated group was proved significant inhibitory effect(p〈0.05). 3. In JFN-${\gamma}$ study, Sochungryong-tang treated group was proved significant inhibitory effect(p〈0.000001). 4. In Total IgE, Sochungryong-tang treated group was proved significant inhibitory effect(p〈0.000001). 5. In OVA-specific IgE, Sochungryong-tang treated group didn't showed significant inhibitory effect. Depending upon above results, it is considered that Sochungryong-tang has the inhibitory effect on the allergic rhinitis of mice and suggested that it could be used in relieving patients of the symptoms which are caused by allergic rhinitis.

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Comparative proteome analysis of seeds of proso millet (Panicum miliaceum) cultivars

  • Roy, Swapan Kumar;Kwon, Soo Jeong;Park, Hyeong-Jun;Yu, Je-Hyeok;Sarker, Kabita;Cho, Seong-Woo;Jung, Tae-Wook;Park, Cheol-Ho;Woo, Sun-Hee
    • Proceedings of the Korean Society of Crop Science Conference
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    • 2017.06a
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    • pp.120-120
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    • 2017
  • Since the composition of proteins from the Korean cultivars of Proso millet is unknown; thereby, the present study was conducted to obtain a reference map of millet seed proteins and identify the functional characteristics of the identified proteins. Proteins extracted from the millet seeds of various cultivars, were investigated using proteomic techniques as 2D electrophoresis coupled with mass fingerprinting. The 1152 (differentially expressed) proteins were detected on 2-D gel. Among them, 26 reproducible protein spots were analyzed by MALDI-TOF-TOF mass spectrometry. Out of 26 proteins, 2 proteins were up-regulated towards all cultivars of millet, while 7 proteins were up-regulated and 13 proteins were down-regulated against only one cultivar. However, abundance in most identified protein species, associated with metabolism, transcription and transcription was significantly enhanced, while that of another protein species involved in polysaccharide metabolism, stress response and pathogenesis were severely reduced. Taken together, the results observed from the study suggest that the differential expression of proteins from the four cultivars of millet may be cultivar-specific. Taken together, a proteomic investigation of millet seeds from different cultivars, we sought to better understand the genetic variation of millet cultivars representing the future millet research, and the functional categorization of individual proteins on the basis of their molecular function.

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Study of anti-Alzheimer Activities from Ginseng Radix Rubra Water Extract by Alzheimer's Protein APP-transgenic Fly (홍삼(紅蔘) 수추출물(水抽出物)이 치매조백질(痴呆蚤白質) APP 형질전환(形質轉換) 초파리에 미치는 영향(影響))

  • Kim, Young-Jun;Kim, Jin-Heong;Yun, Jong-Hyun;Jung, Ejun-Young;Kim, Tae-Heon;Lyu, Yeong-Su;Kang, Hyung-Won
    • Journal of Oriental Neuropsychiatry
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    • v.20 no.1
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    • pp.235-247
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    • 2009
  • Objectives : Ginseng Radix Rubra water extract(RGE) has been used in vivo test for its beneficial effects on neuronal survival and neuroprotective functions, particularly in connection with APP-related dementias and Alzheimer's disease (AD). APP derived from proteolytic processing of the ${\beta}$-amyloid precursor protein (APP), including the amyloid-${\beta}$ peptide (A${\beta}$), plays a critical role in the pathogenesis of Alzheimer's dementia. Methods : We determined that RGE inhibits formation of APP, which are the behavior, and possibly causative, feature of AD. Results and Conclusions : In the cells, RGE significantly activated antiapoptosis and decreased the activity of APP-grim, a key enzyme in the apoptosis cell-signaling cascade. These results suggest that neuronal damage in AD might be due to two factors: a direct APP toxicity and multiple cellular and molecular neuroprotective mechanisms, including attenuation of apoptosis and direct inhibition of APP, underlie the neuroprotective effects of RGE.

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NICKEL INCORPORATION INTO Klebsiella aerogenes UREASE (Klebsiella aerogenes Urease로의 닉켈의 도입)

  • Lee, Mann-Hyung-
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1994.11a
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    • pp.69-80
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    • 1994
  • Although ureases play important roles in microbial nitrogen metabolism and in the pathogenesis of several human diseases, little is known of the mechanism of metallocenter biosynthesis in this Ni-Containing enzyme. Klebsiella aerogenes urease apo-protein was purified from cells grown in the absence of Ni. The purified apo-enzyme showed the same native molecular weight, charge, and subunit stoichiometry as the holo-enzyme. Chemical modification studies were consistent with histidinyl ligation of Ni. Apo-enzyme could not be activated by simple addition of Ni ions suggesting a requirement for a cellular factor. Deletion analysis showed that four accessory genes (ureD, ureE, ureF, and ureG) are necessary for the functional incorporation of the urease metallocenter. Whereas the $\Delta$ureD, $\Delta$ureF, and $\Delta$ureG mutants are inactive and their ureases lack Ni, the $\Delta$ureE mutants retain partial activity and their ureases possess corresponding lower levels of Ni. UreE and UreG peptides were identified by SDS-polyacrylamide gel comparisons of mutant and wild type cells and by N-terminal sequencing. UreD and UreF peptides, which are synthesized at ve교 low levels, were identified by using in vitro transcription/translation methods. Cotransformation of E. coli cells with the complementing plasmids confirmed that ureD and ureF gene products act in trans. UreE was purified and characterized. immunogold electron microscopic studies were used to localize UreE to the cytoplasm. Equilibrium dialysis studies of purified UreE with $^{63}$ NiC1$_2$ showed that it binds ~6 Ni in a specific manner with a $K_{d}$ of 9.6 $\pm$1.3 $\mu$M. Results from spectroscopic studies demonstrated that Ni ions are ligated by 5 histidinyl residues and a sixth N or O atom, consistent with participation of the polyhistidine tail at the carboxyl termini of the dimeric UreE in Ni binding. With these results and other known features of the urease-related gene products, a model for urease metallocenter biosynthesis is proposed in which UreE binds Ni and acts as a Ni donor to the urease apo-protein while UreG binds ATP and couples its Hydrolysis to the Ni incorporation process.ouples its Hydrolysis to the Ni incorporation process.s.

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Upregulation of Heme Oxygenase-1 as an Adaptive Mechanism against Acrolein in RAW 264.7 Macrophages

  • Lee, Nam-Ju;Lee, Seung-Eun;Park, Cheung-Seog;Ahn, Hyun-Jong;Ahn, Kyu-Jeung;Park, Yong-Seek
    • Molecular & Cellular Toxicology
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    • v.5 no.3
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    • pp.230-236
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    • 2009
  • Acrolein, a known toxin in cigarette smoke, is the most abundant electrophilic $\alpha$, $\beta$-unsaturated aldehyde to which humans are exposed in a variety of environmental pollutants, and is also product of lipid peroxidation. Increased unsaturated aldehyde levels and reduced antioxidant status plays a major role in the pathogenesis of various diseases such as diabetes, Alzheimer's and atherosclerosis. The findings reported here show that low concentrations of acrolein induce heme oxygenase-1 (HO-1) expression in RAW 264.7 macrophages. HO-1 induction by acrolein and signal pathways was measured using reverse transcription-polymerase chain reaction, Western blot and immunofluorescence staining analyses. Inhibition of extracellular signal-regulated kinase activity significantly attenuated the induction of HO-1 protein by acrolein, while suppression of Jun N-terminal kinase and p38 activity did not affect induction of HO-1 expression. Moreover, rottlerin, an inhibitor of protein kinase $\delta$, suppressed the upregulation of HO-1 protein production, possibly involving the interaction of NF-E2-related factor 2 (Nrf2), which has a key role as a HO-1 transcription factor. Acrolein elevated the nuclear translocation of Nrf2 in nuclear extraction. The results suggest that RAW 264.7 may protect against acrolein-mediated cellular damage via the upregulation of HO-1, which is an adaptive response to oxidative stress.

Impact of Global and Gene-Specific DNA Methylation in de Novo or Relapsed Acute Myeloid Leukemia Patients Treated with Decitabine

  • Zhang, Li-Ying;Yuan, You-Qing;Zhou, Dong-Ming;Wang, Zi-Yan;Ju, Song-Guang;Sun, Yu;Li, Jun;Fu, Jin-Xiang
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.1
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    • pp.431-437
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    • 2016
  • In this investigation, global DNA methylation patterns and the specific methylation status of 5 genes were studied in DNA from peripheral blood (PB) and impact on progression free survival (PFS) and overall-survival (OS) in patients with de novo or relapsed acute myeloid leukemia (AML) treated with decitabine-based regimens waas assessed. DNA was isolated from PB samples at the time of -1, 1, and 7 days of chemotherapy. Global methylation was determined by ELISA, and the CpG island DNA methylation profile of 5 genes using a DNA methylation PCR system. Our data demonstrated that patients with a high level of 5-mC had a poor prognosis after demethylation therapy and those who have low levels of 5-mC in PB achieved higher CR and better SO, but there was no significant correlation found between the 5-mC levels and other clinical features before treatment except the disease status. Higher methylation status of Sox2 and Oct4 genes was associated with differential response to demethylation therapy. A relatively low methylation percentage in one or both of these two genes was also associated with longer OS after decitabine based chemotherapy. We also suggest that global DNA and Oct-4/Sox2 methylation might impact on the pathogenesis of leukemia and play an important role in the initiation and progression. Moreover, dynamic analysis of 5-mC and Oct-4/Sox2 in peripheral blood nucleated cells of leukemia patients may provide clues to important molecular diagnostic and prognostic targets.

Implications of Sex Hormone Receptor Gene Expression in the Predominance of Hepatocellular Carcinoma in Males: Role of Natural Products

  • Ahmed, Hanaa H;Shousha, Wafaa Gh;Shalby, Aziza B;El-Mezayen, Hatem A;Ismaiel, Nora N;Mahmoud, Nadia S
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.12
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    • pp.4949-4954
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    • 2015
  • The present study was planned to investigate the role of sex hormone receptor gene expression in the pathogenesis of hepatocellular carcinoma (HCC). Adult male Wistar rats were divided into seven groups. Group (1) was negative control. Groups (2), (5), (6), and (7) were orally administered with N-nitrosodiethylamine for the induction of HCC, then group (2) was left untreated, group (5) was orally treated with curcumin, group (6) was orally treated with carvacrol, and group (7) was intraperitoneally injected with doxorubicin, whereas groups (3) and (4) were orally administered only curcumin and carvacrol, respectively. The HCC group showed significant upregulation in the androgen receptor (AR) and the estrogen receptor-alpha ($ER{\alpha}$) gene expression levels in the liver tissue. On the contrary, HCC groups treated with either curcumin or carvacrol showed significant downregulation in AR and $ER{\alpha}$ gene expression levels in the liver tissue. In conclusion, the obtained data highlight that both AR and $ER{\alpha}$ but not estrogen receptor-beta ($ER{\beta}$) gene expression may contribute to the male prevalence of HCC induced in male rats. Interestingly, both curcumin and carvacrol were found to have a promising potency in alleviating the male predominating HCC.

Identification and Characterization of Genes Differentially Expressed in the Resistance Reaction in Wheat Infected with Tilletia tritici, the Common Bunt Pathogen

  • Lu, Zhen-Xiang;Gaudet, Denis A.;Frick, Michele;Puchalski, Byron;Genswein, Bernie;Laroche, Andre
    • BMB Reports
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    • v.38 no.4
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    • pp.420-431
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    • 2005
  • The differentially virulent race T1 of common bunt (Tilletia tritici) was used to inoculate the wheat lines Neepawa (compatible) and its sib BW553 (incompatible) that are nearly isogenic for the Bt-10 resistance gene. Inoculated crown tissues were used to construct a suppression subtractive hybridization (SSH) cDNA library. Of the 1920 clones arrayed from the SSH cDNA library, approximately 10% were differentially regulated. A total of 168 differentially up-regulated and 25 down-regulated genes were identified and sequenced; 71% sequences had significant homology to genes of known function, of which 59% appeared to have roles in cellular metabolism and development, 24% in abiotic/biotic stress responses, 3% involved in transcription and signal transduction responses. Two putative resistance genes and a transcription factor were identified among the up regulated sequences. The expression of several candidate genes including a lipase, two non-specific lipid transfer proteins (ns-LTPs), and several wheat pathogenesis-related (PR)-proteins, was evaluated following 4 to 32 days post-inoculation in compatible and incompatible interactions. Results confirmed the higher overall expression of these genes in resistant BW553 compared to susceptible Neepawa, and the differential up-regulation of wheat lipase, chitinase and PR-1 proteins in the expression of the incompatible interaction.

Association between the Angiotensin-converting Enzyme Gene Insertion/Deletion Polymorphism and Essential Hypertension in Young Pakistani Patients

  • Ismail, Muhammad;Akhtar, Naveed;Nasir, Muhammad;Firasat, Sadaf;Ayub, Qasim;Khaliq, Shagufta
    • BMB Reports
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    • v.37 no.5
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    • pp.552-555
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    • 2004
  • Several studies have demonstrated the importance of angiotensin-converting enzyme (ACE) insertion (I)/deletion (D) polymorphisms in the pathogenesis of hypertension. This study sought to determine the association between the ACE I/D polymorphism and essential hypertension in young Pakistanis. The frequency of the ACE I/D polymorphism was established by a comparative cross-sectional survey of Pakistani patients suffering from essential hypertension and ethnically matched normotensive controls. Samples were collected from tertiary care hospitals in northern Pakistan. Hypertensive individuals were defined as those with a systolic blood pressure > 140 mmHg and/or diastolic blood pressure > 90 mmHg on three separate occasions, or those currently receiving one, or more, anti-hypertensive agents. DNA samples obtained from hypertensive (n=211) and normotensive (n=108) individuals were typed by PCR. The frequency of the ACE I/I genotype was significantly higher in hypertensive patients, aged 20-40 years, than in normotensive controls of the same age group ($\chi^2$ = 4.0, P = 0.041). Whereas no overall significant differences were observed between the I/I, I/D and D/D ACE genotypes (One way ANOVA, F=0.672; P=0.413). The association between the ACE I/I genotype and essential hypertension in individuals aged $\leq$ 40 years suggests that ACE has a role in early onset essential hypertension in Pakistan.