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Novel Mutations in the Displacement Loop of Mitochondrial DNA are Associated with Acute Lymphoblastic Leukemia: A Genetic Sequencing Study

  • Yacoub, Haitham Ahmed;Mahmoud, Wael Mahmoud;El-Baz, Hatim Alaa El-Din;Eid, Ola Mohamed;ELfayoumi, Refaat Ibrahim;Elhamidy, Salem Mohamed;Mahmoud, Maged M.
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.21
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    • pp.9283-9289
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    • 2014
  • Background: Acute lymphoblastic leukemia (ALL) is the most common cancer diagnosed in children and represents approximately 25% of cancer diagnoses among those younger than 15 years of age. Materials and Methods: This study investigated alterations in the displacement loop (d-loop) region of mitochondrial DNA (mtDNA) as a risk factor and diagnostic biomarker for early detection and diagnosis of acute lymphoblastic leukemia. Using mtDNA from 23 subjects diagnosed with acute lymphoblastic leukemia, the first 450 bp of the d-loop region were amplified and successfully sequenced. Results: This revealed 132 mutations at 25 positions in this region, with a mean of 6 alterations per subject. The d-loop alterations in mtDNA in subjects were all identified as single nucleotide polymorphisms in a homoplasmic distribution pattern. Mutant alleles were observed in all subjects with individual frequency rates of up to 95%. Thirteen mutant alleles in the d-loop region of mtDNA occurred with a high frequency. Novel alleles and locations were also identified in the d-loop of mtDNA as follows: 89 G insertions (40%), 95 G insertions (13%), 182 C/T substitutions (5%), 308 C insertions (19%), and 311 C insertions (80%). The findings of this study need to be replicated to be confirmed. Conclusions: Further investigation of the relationship between mutations in mitochondrial d-loop genes and incidence of acute lymphoblastic leukemia is recommended.

Altered Cell to Cell Communication, Autophagy and Mitochondrial Dysfunction in a Model of Hepatocellular Carcinoma: Potential Protective Effects of Curcumin and Stem Cell Therapy

  • Tork, Ola M;Khaleel, Eman F;Abdelmaqsoud, Omnia M
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.18
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    • pp.8271-8279
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    • 2016
  • Background: Hepato-carcinogenesis is multifaceted in its molecular aspects. Among the interplaying agents are altered gap junctions, the proteasome/autophagy system, and mitochondria. The present experimental study was designed to outline the roles of these players and to investigate the tumor suppressive effects of curcumin with or without mesenchymal stem cells (MSCs) in hepatocellular carcinoma (HCC). Materials and Methods: Adult female albino rats were divided into normal controls and animals with HCC induced by diethyl-nitrosamine (DENA) and $CCl_4$. Additional groups treated after HCC induction were: Cur/HCC which received curcumin; MSCs/HCC which received MSCs; and Cur+MSCs/HCC which received both curcumin and MSCs. For all groups there were histopathological examination and assessment of gene expression of connexin43 (Cx43), ubiquitin ligase-E3 (UCP-3), the autophagy marker LC3 and coenzyme-Q10 (Mito.Q10) mRNA by real time, reverse transcription-polymerase chain reaction, along with measurement of LC3II/LC3I ratio for estimation of autophagosome formation in the rat liver tissue. In addition, the serum levels of ALT, AST and alpha fetoprotein (AFP), together with the proinflammatory cytokines $TNF{\alpha}$ and IL-6, were determined in all groups. Results: Histopathological examination of liver tissue from animals which received DENA-$CCl_4$ only revealed the presence of anaplastic carcinoma cells and macro-regenerative nodules. Administration of curcumin, MSCs; each alone or combined into rats after induction of HCC improved the histopathological picture. This was accompanied by significant reduction in ${\alpha}$-fetoprotein together with proinflammatory cytokines and significant decrease of various liver enzymes, in addition to upregulation of Cx43, UCP-3, LC3 and Mito.Q10 mRNA. Conclusions: Improvement of Cx43 expression, nonapoptotic cell death and mitochondrial function can repress tumor growth in HCC. Administration of curcumin and/or MSCs have tumor suppressive effects as they can target these mechanisms. However, further research is still needed to verify their effectiveness.

Antioxidant and Anticholinesterase Potential of Two Nigerian Bitter Yams Using a Simulated Gastrointestinal Digestion Model and Conventional Extraction

  • Salawu, Sule Ola;Ajiboye, Praise Blessing;Akindahunsi, Akintunde Afolabi;Boligon, Aline Augusti
    • Preventive Nutrition and Food Science
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    • v.22 no.2
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    • pp.107-117
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    • 2017
  • The purpose of this study was to evaluate the antioxidant and anticholinesterase activities of yellow and white bitter yams from South Western Nigeria using methanolic extraction and simulated gastrointestinal digestion models. The phenolic compounds in the bitter yam varieties were evaluated by high performance liquid chromatography with a diode array detector (HPLC-DAD). The total phenolic content of the bitter yams was measured by the Folin-Ciocalteu method, reductive potential by assessing the ability of the bitter yam to reduce $FeCl_3$ solution, and the antioxidant activities were determined by the 2,2-diphenyl-1-picrylhydrazyl radical ($DPPH^{\cdot}$) scavenging activity, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radical cation ($ABTS^{{\cdot}+}$) scavenging activity, nitric oxide radical ($NO^{\cdot}$) scavenging ability, hydroxyl radical scavenging ability, and ability to inhibit $Fe^{2+}$-induced lipid oxidation. The HPLC-DAD analysis revealed the presence of some phenolic compounds in the studied bitter yam varieties, with varying degree of quantitative changes after cooking. The antioxidant indices (total phenolic content, total flavonoid content, reducing power, $DPPH^{\cdot}$ scavenging activity, $ABTS^{{\cdot}+}$ scavenging activity, and $NO^{\cdot}$ scavenging activity) were higher in the simulated gastrointestinal digestion model compared to the methanolic extract, with the in vitro digested cooked white bitter yam ranking higher. Similarly, the in vitro digested yams had a higher inhibitory action against lipid oxidation compared to the methanolic extracts, with the cooked white bitter yam ranking high. The methanolic extracts and in vitro enzyme digests showed no acetylcholinesterase inhibitory abilities, while methanolic extracts and the in vitro enzyme digest displayed some level of butyrylcholinesterase inhibitory activities. Therefore the studied bitter yams could be considered as possible health supplements.

E1/E2 of Hepatitis C Virus Genotype-4 and Apoptosis

  • Zekri, Abdel-Rahman N;Sobhy, Esraa;Hussein, Nehal;Ahmed, Ola S;Hussein, Amira;Shoman, Sahar;Soliman, Amira H;El-Din, Hanaa M Alam
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.7
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    • pp.3131-3138
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    • 2016
  • Several studies have addressed the possible role of hepatitis C virus genotype-4 (HCV GT4) in apoptosis. However, this still not fully understood. In the current study a re-constructed clone of E1/E2 polyprotein region of the HCV GT4 was transfected into the Huh7 cell line and a human apoptotic PCR array of 84 genes was used to investigate its possible significance for apoptosis. Out of the 84 genes, only 35 showed significant differential expression, 12 genes being up-regulated and 23 down-regulated. The highest-up regulated genes were APAF1 (apoptotic peptidase-activating factor 1), BID (BH3 interacting domain death agonist) and BCL 10 (B-cell CLL/lymphoma protein 10) with fold regulation of 33.2, 30.1 and 18.9, respectively. The most down-regulated were FAS (TNF receptor super family), TNFRSF10B (tumor necrosis factor receptor super-family member 10b) and FADD (FAS-associated death domain) with fold regulation of -30.2, -27.7 and -14.9, respectively. These results suggest that the E1/E2 proteins may be involved in HCV-induced pathogenesis by modulating apoptosis through the induction of the intrinsic apoptosis pathway and disruption of the BCL2 gene family.

Cooperative Analog and Digital (CANDI) Time Synchronization for Large Multihop Network (다중 홉 네트워크를 위한 디지털 및 아날로그 협동 전송 시간 동기화 프로토콜)

  • Cho, Sung-Hwan;Ingram, Mary Ann
    • The Journal of Korean Institute of Communications and Information Sciences
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    • v.37C no.11
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    • pp.1084-1093
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    • 2012
  • For large multihop networks, large time synchronization (TS) errors can accumulate with conventional methods, such as TPSN, RBS, and FTSP, since they need a large number of hops to cover the network. In this paper, a method combining Concurrent Cooperative Transmission (CCT) and Semi- Cooperative Spectrum Fusion (SCSF) is proposed to reduce the number of hops to cover the large network. In CCT, cooperating nodes transmit the same digitally encoded message in orthogonal channels simultaneously, so receivers can benefit from array and diversity gains. SCSF is an analog cooperative transmission method where different cooperators transmit correlated information simultaneously. The two methods are combined to create a new distributed method of network TS, called the Cooperative Analog and Digital (CANDI) TS protocol, which promises significantly lower network TS errors in multi-hop networks. CANDI and TPSN are compared in simulation for a line network.

Inhibitory Effect of a Decoction of Eucommiae ulmides OLIVER and Dipsacus asperoides C. Y. Cheng et T.M.Ai on Collagen II-induced Arthritis Mice (Collagen II-induced Arthritis 생쥐에 대한 두충(杜仲).속단(續斷) 배합약물의 관절염 억제 효과)

  • Lee, Boo-Kyun;Lee, Young-Cheol;Lee, Jang-Cheon
    • The Korea Journal of Herbology
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    • v.25 no.1
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    • pp.55-63
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    • 2010
  • Objectives : The object of this study was to verify the inhibitory effect of a decoction of Eucommiae ulmides OLIVER (EU) and Dipsacus asperoides C. Y. Cheng et T.M.Ai (DA) on Collagen II-induced Arthritis Mice (CIA mice). Methods : DBA/1OlaHsd mice were immunized with bovine type II collagen. Boostnig same collagen 21 days later, arthritis was induced and then administrated orally the extract of EU+DA (200 or 50 mg/kg) once a day for 4 weeks and compared with that of methotrexate (MTX, 0.3 mg/kg) as a positive control. Results : Administration of EU+DA suppressed the inflammatory progression of CIA mice and the results were 1. Arthritis index of CIA mice was decreased. 2. EU+DA decreased the production of TNF-$\alpha$, IL-6, IL-$1{\beta}$ in the serum of CIA mice. 3. EU+DA decreased the level of IgM. 4. EU+DAincreasaed $CD3^+$, $CD4^+$, $CD4^+$/CD25 but decreased $CD19^+$, $CD3^+/CD49b^+$(NKT), $CD3^-/CD49b^+$(NK), $B220^+/CD23^+$ in PBMC of CIA mice. 5. EU+DA decreased $CD3^+$, $CD4^+$, $CD3^+/CD69^+$ of paw joint in CIA mice. 6. EU+DA decreased subsynovial inflammation. Conclusions : This results demonstrated that extract of EU+DA suppressed the inflammatory progression of CIA mice and supported further studies are required to clarify a mechanism of therapeutic role.

Osseous changes in the temporomandibular joint in rheumatoid arthritis: A cone-beam computed tomography study

  • Rehan, Ola Mohamed;Saleh, Hoda Abdel Kader;Raffat, Hala Ahmed;Abu-Taleb, Noha Saleh
    • Imaging Science in Dentistry
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    • v.48 no.1
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    • pp.1-9
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    • 2018
  • Purpose: To evaluate osseous changes of temporomandibular joint (TMJ) in patients with rheumatoid arthritis (RA) using cone-beam computed tomography (CBCT) and to correlate the imaging findings with the severity of TMJ dysfunction, clinical findings, and laboratory findings. Materials and Methods: This study consisted of 28 subjects, including 14 RA patients and 14 controls, who were scheduled to undergo CBCT imaging for the diagnosis of a complaint not related to or affecting the TMJ. The Fonseca's questionnaire was used to assess the severity of TMJ dysfunction. Rheumatoid factor (RF) and the erythrocyte sedimentation rate (ESR) were assessed in the RA patients. CBCT was then performed in all subjects and osseous TMJ abnormalities were assessed. Results: According to the Fonseca's questionnaire, 14.3% of the patients had no TMJ dysfunction, while 50%, 21.4%, and 14.3% had mild, moderate, and severe dysfunction, respectively. RF was positive in 64.3% of patients, and the ESR level was high in 100%. Imaging findings revealed a statistically significantly higher prevalence of erosion (85.7%), flattening (89.3%), osteophyte formation (32.1%), subchondral cyst (32.1%), sclerosis (64.3%), and condylar irregularities (28.6%) in the RA patients than in the controls. No correlations were found between CBCT findings and the clinical findings, the severity of TMJ dysfunction, disease duration, or laboratory results. Conclusion: RA patients might show extensive osseous abnormalities with no/mild clinical signs or symptoms of TMJ dysfunction that necessitate TMJ imaging for these patients. CBCT is a valuable and efficient modality that can assess osseous TMJ changes in RA patients.

A mothers' perspective on fish and her child's fish consumption in Surakarta, Indonesia

  • Rahmawaty, Setyaningrum;Ramadhani, Farhanah Erwida;Anwar, Innani Kharisma;Puspitasari, Ola;Dewi, Tri Suci Kusuma;Meyer, Barbara J
    • Nutrition Research and Practice
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    • v.15 no.6
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    • pp.761-772
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    • 2021
  • BACKGROUD/OBJECTIVES: Understanding the factors associated with fish consumption is necessary to determine strategies to improve the fish consumption particularly those high in omega-3 long chain polyunsaturated fatty acids (n-3 LCPUFA). The aim of this study was to analyse the correlation between a mother's perspective on fish and actual fish consumption in their children. SUBJECTS/METHODS: Two hundred thirty-one elementary school children grade 3-6 and their mothers in Surakarta were recruited using multi stage random sampling for this study. Data was collected in July and August 2017. A validated questionnaire consisted of 3 topics including knowledge related to the health benefits and organoleptic properties of fish and cooking technique-related attitudes on fish were used to measure the mother's response to the fish properties. A validated food frequency questionnaire and a food picture book of fish specifically designed for the survey were developed and used to assess fish consumption of the children. A χ2 test was used to analyse the correlation between the mothers' perspective on fish and their children's fish consumption. RESULTS: The median fish consumption in children was 65 g/d with fried non-oily or lean fish, e.g., milkfish (locally called Bandeng) and catfish (locally called Lele) were consumed more than oily fish as well as processed fish products. Of all children, 31% met the fish consumption recommended by the Environmental Protection Agency-Food and Drug Administration 2017. There was no relationship between a mother's knowledge related to health benefits, organoleptic properties and cooking technique-related attitude toward fish and her child's fish consumption. CONCLUSIONS: The fish consumption of children is not influenced by their mother's perspective on fish. Nutrition education strategies are warranted to improve fish consumption and maintain the optimal benefits by consuming fish, including fish high in n-3 LCPUFA.

Consecutive versus concomitant follicle-stimulating hormone and highly purified human menopausal gonadotropin: A milder response but better quality

  • Maghraby, Hassan Ali;Agameya, Abdel Fattah Mohamed;Swelam, Manal Shafik;El Dabah, Nermeen Ahmed;Ahmed, Ola Youssef
    • Clinical and Experimental Reproductive Medicine
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    • v.49 no.2
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    • pp.135-141
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    • 2022
  • Objective: This study investigated the impact of two stimulation protocols using highly purified human menopausal gonadotropin (HP-hMG) on the endocrine profile, follicular fluid soluble Fas levels, and outcomes of intracytoplasmic sperm injection (ICSI) cycles. Methods: This prospective clinical trial included 100 normal-responder women undergoing ovarian stimulation for ICSI; 55 patients received concomitant follicle-stimulating hormone (FSH) plus HP-hMG from the start of stimulation, while 45 patients received FSH followed by HP-hMG during mid/late follicular stimulation. The primary outcome was the number of top-quality embryos. The secondary outcomes were the number and percentage of metaphase II (MII) oocytes and the clinical pregnancy rate. Results: The number of MII oocytes was significantly higher in the concomitant protocol (median, 13.0; interquartile range [IQR], 8.5-18.0 vs. 9.0 [8.0-13.0] in the consecutive protocol; p=0.009); however, the percentage of MII oocytes and the fertilization rate were significantly higher in the consecutive protocol (median, 90.91; IQR, 80.0-100.0 vs. 83.33 [75.0-93.8]; p=0.034 and median, 86.67; IQR, 76.9-100.0 vs. 77.78 [66.7-89.9]; p=0.028, respectively). No significant between-group differences were found in top-quality embryos (p=0.693) or the clinical pregnancy rate (65.9% vs. 61.8% in the consecutive vs. concomitant protocol, respectively). The median follicular fluid soluble Fas antigen level was significantly higher in the concomitant protocol (9,731.0 pg/mL; IQR, 6,004.5-10,807.6 vs. 6,350.2 pg/mL; IQR, 4,382.4-9,418.4; p=0.021). Conclusion: Personalized controlled ovarian stimulation using HP-hMG during the late follicular phase led to a significantly lower response, but did not affect the quality of ICSI.

Inhibitory Effect of a decoction composed of Evodia rutaecarpa (Juss.) Benth. and Chaenomeles sinensis Koehne and its component herbal medicines on Collagen II-induced Arthritis Mice (Collagen II-induced Arthritis 생쥐에 대한 오수유(吳茱萸), 목과(木瓜) 및 배합약물의 관절염 억제 효과)

  • Park, Dae-Jung;Lee, Young-Cheol;Lee, Jang-Cheon
    • The Korea Journal of Herbology
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    • v.29 no.4
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    • pp.35-44
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    • 2014
  • Objectives : Evodia rutaecarpa (Juss.) Benth.(ER) and Chaenomeles sinensis Koehne (CS) have multiple applications and were known to have anti-inflammatory effects. In the current study, we investigated to clearly understand the mechanism of therapeutic role for CS, ER and their combination in CIA model mice. Methods : DBA/1OlaHsd mice were immunized with bovine type II collagen. After a second collagen immunization, mice were treated with CS, ER and their combination once a day for 7 weeks. Cytokine production and gene expression were assessed during CIA (collagen-induced arthritis) model mice in knee joint, lymph node (LN) using ELISA and FACS analysis. The severity of arthritis within the knee joints was evaluated by histological assessment of cartilage destruction and pannus formation. Result : Oral administration of CS, ER and their combination (150 mg/kg) significantly suppressed the progression of CIA, and significantly suppressed the progression of CIA and inhibited the production of TNF-${\alpha}$ and IL-6 in serum. The erosion of cartilage was dramatically reduced in mouse knees after treatment with CS plus ER. Conclusion : These result suggest that CS plus ER significantly suppressed the progression of CIA and that this action was characterized by the decreased production of TNF-${\alpha}$, IL-6 and collagen II specific antibody in serum.