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  1. Article ; Online: Intestinal stem cells and inflammation.

    Asfaha, Samuel

    Current opinion in pharmacology

    2015  Volume 25, Page(s) 62–66

    Abstract: The intestinal epithelium is renewed every 3-5 days from at least two principal stem cell pools. Actively cycling crypt based columnar (CBC) Lgr5(+) cells and slower cycling Bmi1-expressing or Krt19-expressing cells maintain the small intestinal and ... ...

    Abstract The intestinal epithelium is renewed every 3-5 days from at least two principal stem cell pools. Actively cycling crypt based columnar (CBC) Lgr5(+) cells and slower cycling Bmi1-expressing or Krt19-expressing cells maintain the small intestinal and colonic epithelium in homeostasis and injury. Following acute epithelial damage, Lgr5+ stem cells are susceptible to injury and a reserve stem cell or progenitor pool is responsible for regeneration of the epithelium. Current data suggests that intestinal stem cells respond to inflammatory signals to modulate their expansion during epithelial regeneration. Here, we review how inflammation and injury affect intestinal and colonic stem cells.
    MeSH term(s) Humans ; Inflammation/pathology ; Inflammation/physiopathology ; Intestinal Mucosa/cytology ; Intestinal Mucosa/pathology ; Intestinal Mucosa/physiology ; Regeneration/physiology ; Stem Cells/cytology ; Stem Cells/physiology
    Language English
    Publishing date 2015-12
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2037057-X
    ISSN 1471-4973 ; 1471-4892
    ISSN (online) 1471-4973
    ISSN 1471-4892
    DOI 10.1016/j.coph.2015.11.008
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: EZH2 inhibition stimulates repetitive element expression and viral mimicry in resting splenic B cells.

    Kim, Seung J / Kiser, Patti K / Asfaha, Samuel / DeKoter, Rodney P / Dick, Frederick A

    The EMBO journal

    2023  Volume 42, Issue 24, Page(s) e114462

    Abstract: Mammalian cells repress expression of repetitive genomic sequences by forming heterochromatin. However, the consequences of ectopic repeat expression remain unclear. Here we demonstrate that inhibitors of EZH2, the catalytic subunit of the Polycomb ... ...

    Abstract Mammalian cells repress expression of repetitive genomic sequences by forming heterochromatin. However, the consequences of ectopic repeat expression remain unclear. Here we demonstrate that inhibitors of EZH2, the catalytic subunit of the Polycomb repressive complex 2 (PRC2), stimulate repeat misexpression and cell death in resting splenic B cells. B cells are uniquely sensitive to these agents because they exhibit high levels of histone H3 lysine 27 trimethylation (H3K27me3) and correspondingly low DNA methylation at repeat elements. We generated a pattern recognition receptor loss-of-function mouse model, called RIC, with mutations in Rigi (encoding for RIG-I), Ifih1 (MDA5), and Cgas. In both wildtype and RIC mutant B cells, EZH2 inhibition caused loss of H3K27me3 at repetitive elements and upregulated their expression. However, NF-κB-dependent expression of inflammatory chemokines and subsequent cell death was suppressed by the RIC mutations. We further show that inhibition of EZH2 in cancer cells requires the same pattern recognition receptors to activate an interferon response. Together, the results reveal chemokine expression induced by EZH2 inhibitors in B cells as a novel inflammatory response to genomic repeat expression. Given the overlap of genes induced by EZH2 inhibitors and Epstein-Barr virus infection, this response can be described as a form of viral mimicry.
    MeSH term(s) Animals ; Mice ; B-Lymphocytes/drug effects ; B-Lymphocytes/metabolism ; DNA Methylation ; Enhancer of Zeste Homolog 2 Protein/antagonists & inhibitors ; Enhancer of Zeste Homolog 2 Protein/genetics ; Enhancer of Zeste Homolog 2 Protein/metabolism ; Epstein-Barr Virus Infections/genetics ; Herpesvirus 4, Human/genetics ; Histones/metabolism ; Repetitive Sequences, Nucleic Acid
    Chemical Substances Enhancer of Zeste Homolog 2 Protein (EC 2.1.1.43) ; Histones
    Language English
    Publishing date 2023-11-07
    Publishing country England
    Document type Journal Article
    ZDB-ID 586044-1
    ISSN 1460-2075 ; 0261-4189
    ISSN (online) 1460-2075
    ISSN 0261-4189
    DOI 10.15252/embj.2023114462
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: CDK4 Inhibitors Thwart Immunity by Inhibiting Phospho-RB-NF-κB Complexes.

    Kim, Seung J / Asfaha, Samuel / Dick, Frederick A

    Molecular cell

    2019  Volume 73, Issue 1, Page(s) 1–2

    Abstract: PD-L1 plays a central role in immune recognition of cancer cells. In this issue of Molecular Cell, Jin et al. (2019) report that a phosphorylated retinoblastoma protein contacts the DNA-binding domain of p65 NF-κB, thereby blocking transcription of PD-L1. ...

    Abstract PD-L1 plays a central role in immune recognition of cancer cells. In this issue of Molecular Cell, Jin et al. (2019) report that a phosphorylated retinoblastoma protein contacts the DNA-binding domain of p65 NF-κB, thereby blocking transcription of PD-L1.
    MeSH term(s) B7-H1 Antigen ; Gene Expression Regulation ; NF-kappa B/genetics ; Retinoblastoma Protein ; Signal Transduction ; Transcription Factor RelA/genetics
    Chemical Substances B7-H1 Antigen ; NF-kappa B ; Retinoblastoma Protein ; Transcription Factor RelA
    Language English
    Publishing date 2019-01-04
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 1415236-8
    ISSN 1097-4164 ; 1097-2765
    ISSN (online) 1097-4164
    ISSN 1097-2765
    DOI 10.1016/j.molcel.2018.12.012
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: F4/80

    Shin, Alice E / Tesfagiorgis, Yodit / Larsen, Frederikke / Derouet, Mathieu / Zeng, Peter Y F / Good, Hayley J / Zhang, Liyue / Rubinstein, Mara R / Han, Yiping W / Kerfoot, Steven M / Nichols, Anthony C / Hayakawa, Yoku / Howlett, Christopher J / Wang, Timothy C / Asfaha, Samuel

    Gastroenterology

    2023  Volume 164, Issue 4, Page(s) 593–609.e13

    Abstract: Background & aims: Colorectal cancer is a leading cause of cancer death, and a major risk factor is chronic inflammation. Despite the link between colitis and cancer, the mechanism by which inflammation leads to colorectal cancer is not well understood.! ...

    Abstract Background & aims: Colorectal cancer is a leading cause of cancer death, and a major risk factor is chronic inflammation. Despite the link between colitis and cancer, the mechanism by which inflammation leads to colorectal cancer is not well understood.
    Methods: To investigate whether different forms of inflammation pose the same risk of cancer, we compared several murine models of colitis (dextran sodium sulfate [DSS], 2,4,6-trinitrobenzene sulfonic acid, 4-ethoxylmethylene-2-phenyloxazol-5-one, Citrobacter rodentium, Fusobacterium nucleatum, and doxorubicin) with respect to their ability to lead to colonic tumorigenesis. We attempted to correlate the severity of colitis and inflammatory profile with the risk of tumorigenesis in both azoxymethane-dependent and Dclk1/APC
    Results: DSS colitis reproducibly led to colonic tumors in both mouse models of colitis-associated cancer. In contrast, all other forms of colitis did not lead to cancer. When compared with the colitis not associated with tumorigenesis, DSS colitis was characterized by significantly increased CD11b
    Conclusions: We have identified CD11b
    MeSH term(s) Animals ; Mice ; Azoxymethane ; Carcinogenesis/metabolism ; Cell Plasticity ; Colitis/chemically induced ; Colitis/complications ; Colitis/metabolism ; Colitis-Associated Neoplasms/metabolism ; Dextran Sulfate/toxicity ; Disease Models, Animal ; Inflammation/metabolism ; Macrophages/metabolism ; Mice, Inbred C57BL
    Chemical Substances Azoxymethane (MO0N1J0SEN) ; Dextran Sulfate (9042-14-2) ; Ly-6C antigen, mouse
    Language English
    Publishing date 2023-01-10
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 80112-4
    ISSN 1528-0012 ; 0016-5085
    ISSN (online) 1528-0012
    ISSN 0016-5085
    DOI 10.1053/j.gastro.2023.01.002
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Non-Steroidal Anti-Inflammatory Drugs (NSAIDs): Usage and co-prescription with other potentially interacting drugs in elderly: A cross-sectional study.

    Abdu, Nuru / Mosazghi, Asmerom / Teweldemedhin, Samuel / Asfaha, Luwam / Teshale, Makda / Kibreab, Mikal / Anand, Indermeet Singh / Tesfamariam, Eyasu H / Russom, Mulugeta

    PloS one

    2020  Volume 15, Issue 10, Page(s) e0238868

    Abstract: Globally, usage of non-steroidal anti-inflammatory drugs (NSAIDs) in elderly with chronic pain has been reported as frequent. Though NSAIDs are fundamental in maintaining their quality of life, the risk of polypharmacy, drug interactions and adverse ... ...

    Abstract Globally, usage of non-steroidal anti-inflammatory drugs (NSAIDs) in elderly with chronic pain has been reported as frequent. Though NSAIDs are fundamental in maintaining their quality of life, the risk of polypharmacy, drug interactions and adverse effects is of paramount importance as the elderly usually require multiple medications for their co-morbidities. If prescriptions are not appropriately monitored and managed, they are likely to expose patients to serious drug interactions and potentially fatal adverse effects. This study was conducted to assess the appropriateness of NSAIDs use and determine the risk of NSAIDs related potential interactions in elderly. An analytical cross-sectional study was conducted among elderly out-patients (aged 60 and above) who visited three hospitals in Asmara, Eritrea, between August 22 and September 29, 2018. A stratified random sampling design was employed and data was collected using an interview-based questionnaire and by abstracting information from patients' prescriptions and medical cards. Descriptive and analytical statistics including chi-square test and logistic regression were employed using IBM SPSS (version 22). A total of 285 respondents were enrolled in the study with similar male to female ratio. One in four of all respondents were chronic NSAIDs users and NSAIDs risk practice was reported in 24%. Using chronic NSAIDs without prophylactic gastro-protective agents, self-medication, polypharmacy and drug-drug interactions were the main problems identified. A total of 322 potential interactions in 205 patients were identified and of which, 97.2% were classified as moderate, 0.6% severe and the rest were mild. Those who involved in self-medication were more likely to be exposed to drug interactions. Diabetes (AOR = 2.39, 95% CI: 1.14, 5.02) and hypertension (AOR = 9.06, 95% CI: 4.00, 20.51) were associated with chronic NSAIDs use and incidence of potential drug interactions (AOR = 3.5, 95%CI: 1.68, 4.3; AOR = 2.81, 95%CI: 1.61, 4.9 respectively), while diabetes AOR = 4.5, 95% CI: 2.43, 8.35) and cardiac problems (AOR = 4.29, 95% CI: 1.17, 15.73) were more likely to be associated with incidence of polypharmacy. In conclusion, chronic use of NSAIDs without gastro-protective agents and therapeutic duplication of NSAIDs were commonly which requires attention from programmers, health facility managers and healthcare professionals to safeguard elderlies from preventable harm.
    MeSH term(s) Aged ; Aged, 80 and over ; Anti-Inflammatory Agents, Non-Steroidal/administration & dosage ; Anti-Inflammatory Agents, Non-Steroidal/adverse effects ; Anti-Inflammatory Agents, Non-Steroidal/therapeutic use ; Chronic Disease ; Cross-Sectional Studies ; Drug Interactions ; Eritrea ; Female ; Humans ; Logistic Models ; Male ; Middle Aged ; Polypharmacy ; Quality of Life ; Self Medication/statistics & numerical data ; Surveys and Questionnaires
    Chemical Substances Anti-Inflammatory Agents, Non-Steroidal
    Language English
    Publishing date 2020-10-09
    Publishing country United States
    Document type Journal Article
    ISSN 1932-6203
    ISSN (online) 1932-6203
    DOI 10.1371/journal.pone.0238868
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Performance report cards increase adenoma detection rate.

    Sey, Michael Sai Lai / Liu, Andy / Asfaha, Samuel / Siebring, Victoria / Jairath, Vipul / Yan, Brian

    Endoscopy international open

    2017  Volume 5, Issue 7, Page(s) E675–E682

    Abstract: Background and study aims: Adenoma detection rate (ADR) is an important measure of colonoscopy quality, as are polyp, advanced ADR, and adenocarcinoma detection rates. We investigated whether performance report cards improved these outcome measures.: ... ...

    Abstract Background and study aims: Adenoma detection rate (ADR) is an important measure of colonoscopy quality, as are polyp, advanced ADR, and adenocarcinoma detection rates. We investigated whether performance report cards improved these outcome measures.
    Patients and methods: Endoscopists were given report cards comparing their detection rates to the institutional mean on an annual basis. Detection rates were evaluated at baseline, 1 year after report cards (Year 1), and 2 years after report cards (Year 2). Endoscopists were unaware of the study and received no other interventions. The primary outcome was ADR and secondary outcomes were polyp detection rate (PDR), advanced ADR, and adenocarcinoma detection rate. Multivariate regression was performed to adjust for temporal trends in patient, endoscopists, and procedural factors.
    Results:  Seventeen physicians performed 3,118 screening colonoscopies in patients with positive FOBT or family history of colon cancer. The ADR increased from 34.5 % (baseline) to 39.4 % (Year 1) and 41.2 % (Year 2) (
    Conclusions:  Annual performance report cards increased adenoma detection rates, especially among physicians with low ADR < 25 %.
    Language English
    Publishing date 2017-07-06
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 2761052-4
    ISSN 2196-9736 ; 2364-3722
    ISSN (online) 2196-9736
    ISSN 2364-3722
    DOI 10.1055/s-0043-110568
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)

    Nuru Abdu / Asmerom Mosazghi / Samuel Teweldemedhin / Luwam Asfaha / Makda Teshale / Mikal Kibreab / Indermeet Singh Anand / Eyasu H Tesfamariam / Mulugeta Russom

    PLoS ONE, Vol 15, Iss 10, p e

    Usage and co-prescription with other potentially interacting drugs in elderly: A cross-sectional study.

    2020  Volume 0238868

    Abstract: Globally, usage of non-steroidal anti-inflammatory drugs (NSAIDs) in elderly with chronic pain has been reported as frequent. Though NSAIDs are fundamental in maintaining their quality of life, the risk of polypharmacy, drug interactions and adverse ... ...

    Abstract Globally, usage of non-steroidal anti-inflammatory drugs (NSAIDs) in elderly with chronic pain has been reported as frequent. Though NSAIDs are fundamental in maintaining their quality of life, the risk of polypharmacy, drug interactions and adverse effects is of paramount importance as the elderly usually require multiple medications for their co-morbidities. If prescriptions are not appropriately monitored and managed, they are likely to expose patients to serious drug interactions and potentially fatal adverse effects. This study was conducted to assess the appropriateness of NSAIDs use and determine the risk of NSAIDs related potential interactions in elderly. An analytical cross-sectional study was conducted among elderly out-patients (aged 60 and above) who visited three hospitals in Asmara, Eritrea, between August 22 and September 29, 2018. A stratified random sampling design was employed and data was collected using an interview-based questionnaire and by abstracting information from patients' prescriptions and medical cards. Descriptive and analytical statistics including chi-square test and logistic regression were employed using IBM SPSS (version 22). A total of 285 respondents were enrolled in the study with similar male to female ratio. One in four of all respondents were chronic NSAIDs users and NSAIDs risk practice was reported in 24%. Using chronic NSAIDs without prophylactic gastro-protective agents, self-medication, polypharmacy and drug-drug interactions were the main problems identified. A total of 322 potential interactions in 205 patients were identified and of which, 97.2% were classified as moderate, 0.6% severe and the rest were mild. Those who involved in self-medication were more likely to be exposed to drug interactions. Diabetes (AOR = 2.39, 95% CI: 1.14, 5.02) and hypertension (AOR = 9.06, 95% CI: 4.00, 20.51) were associated with chronic NSAIDs use and incidence of potential drug interactions (AOR = 3.5, 95%CI: 1.68, 4.3; AOR = 2.81, 95%CI: 1.61, 4.9 respectively), while diabetes ...
    Keywords Medicine ; R ; Science ; Q
    Subject code 360
    Language English
    Publishing date 2020-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: Tff2 defines transit-amplifying pancreatic acinar progenitors that lack regenerative potential and are protective against Kras-driven carcinogenesis.

    Jiang, Zhengyu / Wu, Feijing / Laise, Pasquale / Takayuki, Tanaka / Na, Fu / Kim, Woosook / Kobayashi, Hiroki / Chang, Wenju / Takahashi, Ryota / Valenti, Giovanni / Sunagawa, Masaki / White, Ruth A / Macchini, Marina / Renz, Bernhard W / Middelhoff, Moritz / Hayakawa, Yoku / Dubeykovskaya, Zinaida A / Tan, Xiangtian / Chu, Timothy H /
    Nagar, Karan / Tailor, Yagnesh / Belin, Bryana R / Anand, Akanksha / Asfaha, Samuel / Finlayson, Michael O / Iuga, Alina C / Califano, Andrea / Wang, Timothy C

    Cell stem cell

    2023  Volume 30, Issue 8, Page(s) 1091–1109.e7

    Abstract: While adult pancreatic stem cells are thought not to exist, it is now appreciated that the acinar compartment harbors progenitors, including tissue-repairing facultative progenitors (FPs). Here, we study a pancreatic acinar population marked by trefoil ... ...

    Abstract While adult pancreatic stem cells are thought not to exist, it is now appreciated that the acinar compartment harbors progenitors, including tissue-repairing facultative progenitors (FPs). Here, we study a pancreatic acinar population marked by trefoil factor 2 (Tff2) expression. Long-term lineage tracing and single-cell RNA sequencing (scRNA-seq) analysis of Tff2-DTR-CreER
    MeSH term(s) Humans ; Pancreatic Neoplasms/genetics ; Trefoil Factor-2/metabolism ; Carcinoma, Pancreatic Ductal/genetics ; Carcinoma, Pancreatic Ductal/metabolism ; Pancreas/metabolism ; Acinar Cells/metabolism ; Carcinogenesis/genetics ; Carcinogenesis/metabolism
    Chemical Substances Trefoil Factor-2
    Language English
    Publishing date 2023-08-02
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 2375354-7
    ISSN 1875-9777 ; 1934-5909
    ISSN (online) 1875-9777
    ISSN 1934-5909
    DOI 10.1016/j.stem.2023.07.002
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Book: Remunerating commodity producers in developing countries

    Asfaha, Samuel G

    regulating concentration in commodity markets

    (Research papers / Trade-Related Agenda, Development and Equity (T.R.A.D.E.), South Centre ; 2)

    2005  

    Author's details by Samuel G. Asfaha. [South Centre]
    Series title Research papers / Trade-Related Agenda, Development and Equity (T.R.A.D.E.), South Centre ; 2
    Keywords Agrarpreis ; Kaffee ; Kaffeemarkt ; Marktstruktur ; Entwicklungsländer
    Language English
    Size 29 S., graph. Darst., 30 cm
    Publisher South Centre
    Publishing place Geneva
    Document type Book
    Database ECONomics Information System

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  10. Article ; Online: Atoh1

    Castillo-Azofeifa, David / Fazio, Elena N / Nattiv, Roy / Good, Hayley J / Wald, Tomas / Pest, Michael A / de Sauvage, Frederic J / Klein, Ophir D / Asfaha, Samuel

    The EMBO journal

    2019  Volume 38, Issue 4

    Abstract: During homeostasis, the colonic epithelium is replenished every 3-5 days by rapidly ... ...

    Abstract During homeostasis, the colonic epithelium is replenished every 3-5 days by rapidly cycling
    MeSH term(s) Animals ; Basic Helix-Loop-Helix Transcription Factors/genetics ; Basic Helix-Loop-Helix Transcription Factors/metabolism ; Cells, Cultured ; Colitis/chemically induced ; Colitis/pathology ; Colitis/prevention & control ; Colon/cytology ; Colon/physiology ; Homeostasis ; Intestine, Small/cytology ; Intestine, Small/physiology ; Keratin-19/genetics ; Keratin-19/metabolism ; Mice ; Receptor, Notch1/genetics ; Receptor, Notch1/metabolism ; Receptors, G-Protein-Coupled/genetics ; Receptors, G-Protein-Coupled/metabolism ; Regeneration ; Stem Cells/cytology ; Stem Cells/physiology
    Chemical Substances Atoh1 protein, mouse ; Basic Helix-Loop-Helix Transcription Factors ; Keratin-19 ; Lgr5 protein, mouse ; Notch1 protein, mouse ; Receptor, Notch1 ; Receptors, G-Protein-Coupled
    Language English
    Publishing date 2019-01-11
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 586044-1
    ISSN 1460-2075 ; 0261-4189
    ISSN (online) 1460-2075
    ISSN 0261-4189
    DOI 10.15252/embj.201899984
    Database MEDical Literature Analysis and Retrieval System OnLINE

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