Article
Biology
Valentina Kugler, Andreas Lieb, Nathan Guerin, Bruce R. Donald, Eduard Stefan, Teresa Kaserer
Summary: We introduce an Osprey-based computational protocol that can prospectively identify oncogenic mutations by disrupting molecular interactions. This protocol can be used to analyze protein-protein and protein-DNA interfaces and has been validated on a dataset of clinically relevant mutations. Furthermore, it successfully predicts previously uncharacterized patient mutations in CDK6 and p16 genes, which have been experimentally confirmed to impair complex formation. The Disruptor algorithm evaluates whether mutations disrupt protein-protein and protein-DNA interactions and calculates the relative probabilities of specific mutations, identifying those with a high probability of becoming clinically relevant for carcinogenesis.
COMMUNICATIONS BIOLOGY
(2023)
Article
Oncology
Luis I. Prieto, Ines Sturmlechner, Sara I. Graves, Cheng Zhang, Nick P. Goplen, Eunhee S. Yi, Jie Sun, Hu Li, Darren J. Baker
Summary: In an oncogenic Kras-driven lung cancer mouse model, senescent cells, specifically alveolar macrophages, accumulate early in neoplasia. These macrophages have upregulated expression of p16INK4a and Cxcr1, are distinct from previously defined subsets, and suppress cytotoxic T cell responses. The removal of these cells attenuates adenoma development and progression in mice, suggesting their tumorigenesis-promoting role. Notably, alveolar macrophages with these properties increase with normal aging in mouse lung and in human lung adenocarcinoma in situ. Overall, targeting senescent macrophages may attenuate lung cancer progression during the early stages of disease.
Article
Biotechnology & Applied Microbiology
Satbir Thakur, Yibing Ruan, Chunfen Zhang, Xueqing Lun, Aarthi Jayanthan, Aru Narendran
Summary: AT/RT is a rare, aggressive tumor with a common molecular defect of hSNF5 gene loss. A modified VVDD expressing wild type hSNF5 gene has been developed to potentially increase efficacy against AT/RT.
CANCER GENE THERAPY
(2021)
Article
Multidisciplinary Sciences
Ruchi Kumari, Holger Hummerich, Xu Shen, Martin Fischer, Larisa Litovchick, Sibylle Mittnacht, James A. DeCaprio, Parmjit S. Jat
Summary: Cellular senescence is a stable cell cycle arrest that normal cells undergo after a finite number of divisions, largely established and maintained by the p53/p21(WAF1/CIP1) and pRB/p16(INK4A) tumour suppressor pathways. The DREAM complex plays a crucial role in senescence, with re-entry into the cell cycle bypassing senescence.
SCIENTIFIC REPORTS
(2021)
Article
Food Science & Technology
Eunsol Seo, Hee Ho Song, Heebal Kim, Byung-Yong Kim, ShinJae Park, Hyung Joo Suh, Yejin Ahn
Summary: The protective effect of mixed probiotics against UVB-induced photoaging in both cells and mice was investigated in this study. The probiotics significantly improved skin moisture, transepidermal water loss, erythema, and skin thickness. They also suppressed wrinkle formation by regulating the expression of matrix metalloproteinases and tissue inhibitors of MMPs. In addition, the probiotics reduced inflammatory cytokine levels and phosphorylation of certain proteins in the MAPK pathway. The study also found that the probiotics modulated the gut microbiome and increased the abundance of Lactobacillus and Akkermansia.
MOLECULAR NUTRITION & FOOD RESEARCH
(2023)
Article
Oncology
Kamini Singh, Jianan Lin, Nicolas Lecomte, Prathibha Mohan, Askan Gokce, Viraj R. Sanghvi, Man Jiang, Olivera Grbovic-Huezo, Antonija Burcul, Stefan G. Stark, Paul B. Romesser, Qing Chang, Jerry P. Melchor, Rachel K. Beyer, Mark Duggan, Yoshiyuki Fukase, Guangli Yang, Ouathek Ouerfelli, Agnes Viale, Elisa de Stanchina, Andrew W. Stamford, Peter T. Meinke, Gunnar Raetsch, Steven D. Leach, Zhengqing Ouyang, Hans-Guido Wendel
Summary: This study demonstrates the crucial role of the eIF4A RNA helicase in pancreatic adenocarcinoma (PDAC), particularly in the KRAS signaling pathway. Through ribosome footprinting in conjunction with deep RNA sequencing, eIF4A-dependent mRNAs in PDAC were accurately identified. These findings reveal the therapeutic mechanism of eIF4A inhibitors in PDAC.
Article
Biochemistry & Molecular Biology
Isaac P. Horn, David L. Marks, Amanda N. Koenig, Tara L. Hogenson, Luciana L. Almada, Lauren E. Goldstein, Paola A. Romecin Duran, Renzo Vera, Anne M. Vrabel, Gaofeng Cui, Kari G. Rabe, William R. Bamlet, Georges Mer, Hugues Sicotte, Cheng Zhang, Hu Li, Gloria M. Petersen, Martin E. Fernandez-Zapico
Summary: Germline mutations in the CDKN2A gene, such as the 47T>G variant, lead to reduced expression and diminished function of the p16 protein, increasing the risk of pancreatic cancer. Cells with the p16-L16R mutation showed faster growth and survival rates compared to cells with wild-type p16, indicating the potential impact of this mutation on cancer development.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Chemistry, Analytical
Sinemyiz Atalay, Agnieszka Gegotek, Adam Wronski, Pedro Domigues, Elzbieta Skrzydlewska
Summary: The study evaluated the effect of CBD on the metabolism of skin keratinocytes in nude rats exposed to UVA/UVB radiation. The results show that CBD can protect keratinocytes from UV-induced metabolic changes by maintaining proteostasis and reducing inflammation and redox imbalance.
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
(2021)
Article
Pathology
Mikhail S. Ermakov, Karl Kashofer, Sigrid Regauer
Summary: This study compared the genetic alterations driving penile squamous cell carcinomas (SCC) induced by HPV and those independent of HPV. The results showed that HPV-induced SCC had fewer gene mutations compared to HPV-independent SCC, suggesting different mechanisms of carcinogenesis. These findings provide valuable insights for the development of targeted therapies for penile SCC of different etiologies.
Article
Oncology
Brent A. Willobee, Alexander A. Gaidarski, Austin R. Dosch, Jason A. Castellanos, Xizi Dai, Siddharth Mehra, Fanuel Messaggio, Supriya Srinivasan, Michael N. VanSaun, Nagaraj S. Nagathihalli, Nipun B. Merchant
Summary: The expression of p16 is significantly reduced in PDAC tumors, while combination of MEKi and CDK4/6i can significantly decrease cell proliferation in PDAC cells. By promoting senescence-mediated growth arrest, MEKi with CDK4/6i reduces tumor cell proliferation and attenuates tumor growth in PDAC models.
MOLECULAR CANCER THERAPEUTICS
(2021)
Article
Food Science & Technology
Ruixue Zhang, Ying Wei, Jiangtao Zhang, Muyi Cai, Lu Lu, Lei Fang, Xiuyuan Qin, Ruizeng Gu
Summary: The study demonstrated the beneficial effects of rice protein hydrolysate (RPH) and its characteristic peptides on UVB-induced photodamage in guinea pigs. RPH improved antioxidant capacity, prevented water and collagen loss, and protected skin tissue by regulating signaling pathways. LPK and pEK were identified as key peptides in promoting collagen expression.
JOURNAL OF FUNCTIONAL FOODS
(2021)
Article
Chemistry, Medicinal
Hoon Kim, Soon Yeong Park, Dae Kyun Chung
Summary: The study showed that oral administration of OBS-E could significantly improve skin function in hairless mice damaged by UVB radiation, including reducing wrinkles, increasing skin elasticity and hyaluronic acid content, decreasing transepidermal water loss, as well as reducing epidermal thickness and inhibiting inflammatory reactions.
Article
Oncology
Felix Oppel, Senyao Shao, Sarah Gendreizig, Mark W. Zimmerman, Matthias Schurmann, Viyof Ful Flavian, Peter Goon, Susan N. Chi, Jon C. Aster, Holger Sudhoff, A. Thomas Look
Summary: Loss of the SMARCB1 gene drives the development of malignant tumors. Using CRISPR-Cas9, researchers successfully created smarcb1 deficiency in zebrafish and found that it leads to the development of various malignancies in combination with mutant p53. Disruption of p53 was found to be necessary for smarcb1-deficient tumors, suggesting alternative mechanisms for attenuating p53 signaling in human tumors. Small molecule-mediated disruption of the p53-MDM2 interaction stabilized p53 protein, leading to p53-pathway reactivation, cell-cycle arrest, and increased apoptosis, which could be a potential treatment strategy for human epithelioid sarcoma. Additionally, MDM2 inhibition and the topoisomerase II inhibitor doxorubicin synergize in targeting epithelioid sarcoma cell viability.
MOLECULAR CANCER THERAPEUTICS
(2022)
Article
Biochemistry & Molecular Biology
Yuan-Lin He, Liyuan Lin, Haiyan Zheng, Yinhuan Mo, Chunxia Zhou, Shengli Sun, Pengzhi Hong, Zhong-Ji Qian
Summary: This study suggests that AYAPE has anti-skin aging properties by alleviating DNA damage, reducing intracellular reactive oxygen levels, and down regulating phosphorylation of proteins in the MAPK/AP-1 signaling pathways. AYAPE also attenuates senescence in cells and shows a direct combination with p53. Overall, AYAPE has the potential to combat skin aging.
JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY
(2022)
Article
Chemistry, Medicinal
Ji-yue Sha, Jian-hao Li, Yan-dan Zhou, Jia-yu Yang, Wei Liu, Shuang Jiang, Ying-ping Wang, Rui Zhang, Peng Di, Wei Li
Summary: The study demonstrates that maltol can improve aging-induced liver and kidney injuries by activating certain proteins and antioxidant enzymes to reduce oxidative stress injury. Maltol also improves oxidative stress injury by activating the PI3K/Akt signaling pathway.
PHYTOTHERAPY RESEARCH
(2021)
Article
Medical Laboratory Technology
Hamdy E. A. Ali, Ahmed A. Emam, Ahmed A. Zeeneldin, Reham Srour, Reda Tabashy, Eman D. El-Desouky, Zakaria Y. Abd Elmageed, Abdel-Hady A. Abdel-Wahab
CLINICAL BIOCHEMISTRY
(2019)
Article
Multidisciplinary Sciences
Shaimaa A. Gad, Hamdy E. A. Ali, Rofaida Gaballa, Rania M. Abdelsalam, Mourad Zerfaoui, Hamed I. Ali, Salwa H. Salama, Sanaa A. Kenawy, Emad Kandil, Zakaria Y. Abd Elmageed
SCIENTIFIC REPORTS
(2019)
Review
Cell Biology
Saber H. Saber, Hamdy E. A. Ali, Rofaida Gaballa, Mohamed Gaballah, Hamed Ali, Mourad Zerfaoui, Zakaria Y. Abd Elmageed
Article
Multidisciplinary Sciences
Hetty E. Carraway, Sridhar A. Malkaram, Yana Cen, Aymen Shatnawi, Jun Fan, Hamdy E. A. Ali, Zakaria Y. Abd Elmageed, Thomm Buttolph, James Denvir, Donald A. Primerano, Tamer E. Fandy
SCIENTIFIC REPORTS
(2020)
Correction
Multidisciplinary Sciences
Hetty E. Carraway, Sridhar A. Malkaram, Yana Cen, Aymen Shatnawi, Jun Fan, Hamdy E. A. Ali, Zakaria Y. Abd Elmageed, Thomm Buttolph, James Denvir, Donald A. Primerano, Tamer E. Fandy
SCIENTIFIC REPORTS
(2020)
Article
Oncology
Rofaida Gaballa, Hamdy E. A. Ali, Mohamed O. Mahmoud, Johng S. Rhim, Hamed Ali, Heba F. Salem, Mohammad Saleem, Mohamed A. Kandeil, Stefan Ambs, Zakaria Y. Abd Elmageed
Review
Cell Biology
Mourad Zerfaoui, Titilope Modupe Dokunmu, Eman Ali Toraih, Bashir M. Rezk, Zakaria Y. Abd Elmageed, Emad Kandil
Summary: The link between melanoma and thyroid cancer may be due to specific gene mutations leading to tumor aggressiveness. Studies indicate an increased mutual risk between melanoma patients and thyroid cancer patients compared to healthy individuals.
Article
Cell Biology
Rania Makboul, Islam F. Abdelkawi, Dalia M. Badary, Mahmoud R. A. Hussein, Johng S. Rhim, Eman A. Toraih, Mourad Zerfaoui, Zakaria Y. Abd Elmageed
Summary: TMTC4 expression was found to be significantly higher in PCa cells and tissues compared to BPH and normal cells, with strong cytoplasmic expressions in PCa cases. The protein showed high sensitivity and specificity in differentiating between PCa and BPH, indicating its potential for clinical application.
Article
Oncology
Mourad Zerfaoui, Eman Toraih, Emmanuelle Ruiz, Youssef Errami, Abdallah S. Attia, Moroz Krzysztof, Zakaria Y. Abd Elmageed, Emad Kandil
Summary: This study investigates the role of nuclear BRAF(V600E) and its partner HMOX1 in melanoma aggressiveness and drug resistance. The findings provide valuable insights into the mechanisms of drug resistance and offer potential prognostic markers and therapeutic strategies for metastatic melanoma.
Article
Oncology
Hamdy E. A. Ali, Mohamed S. A. Gaballah, Rofaida Gaballa, Shahenda Mahgoub, Zeinab A. Hassan, Eman A. Toraih, Bettina F. Drake, Zakaria Y. Abd Elmageed
Summary: Novel sEV-associated miRs, including miR-6068 and miR-1915-3p, were found to be enriched in PCa patients, with miR-6716-5p and miR-3692-3p distinguishing between AA and CA men and low and high Gleason score. Among these miRs, miR-1915-3p emerged as an independent prognostic marker for longer recurrence-free survival.
Article
Biology
Naif E. Al Omairi, Ashraf Albrakati, Khalaf F. Alsharif, Abdulraheem S. Almalki, Walaa Alsanie, Zakaria Y. Abd Elmageed, Dalia Zaafar, Maha S. Lokman, Amira A. Bauomy, Saied K. Belal, Mohamed M. Abdel-Daim, Ahmed E. Abdel Moneim, Hussain Alyami, Rami B. Kassab
Summary: The study found that SeNPs-PDG has the potential to be an anticonvulsant agent. It delayed the onset of epileptic seizures and reduced their duration. It also protected against hippocampal cell loss, oxidative stress, and neuroinflammation. Additionally, SeNPs-PDG restored the balance between excitatory and inhibitory neurotransmitters and improved monoaminergic and cholinergic transmission.
Article
Oncology
Abu Bakar Siddique, Hassan Y. Ebrahim, Afsana Tajmim, Judy Ann King, Khaldoun S. Abdelwahed, Zakaria Y. Abd Elmageed, Khalid A. El Sayed
Summary: A compound called S-(-)-oleocanthal (OC), found in extra-virgin olive oil, can inhibit the growth and relapse of aggressive prostate cancer. OC works by suppressing an important enzyme called SMYD2, which is responsible for activating several proteins involved in prostate cancer. It has shown stronger anticancer activity in animal models compared to other SMYD2 inhibitors and is a potential natural compound for use in prostate cancer patients as a dietary supplement.
Article
Chemistry, Medicinal
Hoda A. Salem, Nehal Elsherbiny, Sharifa Alzahrani, Hanan M. Alshareef, Zakaria Y. Abd Elmageed, Sadeem M. Ajwah, Ahmed M. E. Hamdan, Yahia S. Abdou, Omneya O. Galal, Marwa K. A. El Azazy, Karema Abu-Elfotuh
Summary: Monosodium glutamate (MSG) is widely used in food, but it has been linked to protein malnutrition and various toxicities. This study explores the association between MSG, protein malnutrition, and brain injury similar to attention-deficit/hyperactivity disorder (ADHD). It also investigates the potential protective effects of morin hydrate (MH), a natural flavonoid. The findings suggest that MSG and/or protein malnutrition are associated with neuronal dysfunction, and MH may offer neuroprotection by targeting specific signaling pathways.
Article
Biochemistry & Molecular Biology
Emmanuelle M. Ruiz, Solomon A. Alhassan, Youssef Errami, Zakaria Y. Abd Elmageed, Jennifer S. Fang, Guangdi Wang, Margaret A. Brooks, Joe A. Abi-Rached, Emad Kandil, Mourad Zerfaoui
Summary: A 13-gene panel was identified to accurately predict resistance to BRAF/MEK inhibitor therapy in melanoma patients. Dysregulation of HMOX1, ICAM, MMP2, and SPARC defined a treatment-resistant landscape, and HMOX1-mediated mitochondrial stress response was identified as a potential key driver of resistance. These findings highlight the importance of these genes in predicting treatment outcomes and targeting underlying mechanisms to reduce resistance development.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Medicinal
Khaldoun S. Abdelwahed, Abu Bakar Siddique, Hassan Y. Ebrahim, Mohammed H. Qusa, Ethar A. Mudhish, Ashkan H. Rad, Mourad Zerfaoui, Zakaria Y. Abd Elmageed, Khalid A. El Sayed
Summary: Metastatic castration-resistant prostate cancer (mCRPC) cells can synthesize their own cholesterol and overexpress proprotein convertase subtilisin/kexin type 9 (PCSK9). Knockdown of PCSK9 leads to reduced migration and colony formation in mCRPC cells. Higher expression of PCSK9 is associated with older age and early Gleason scores. The fermentation product pseurotin A (PS) suppresses PCSK9 expression and protein-protein interactions, as well as cancer recurrence. PS treatment inhibits migration and colony formation in mCRPC cells. In a mouse model, a high-fat diet increases tumor volume, metastasis, cholesterol, LDL-C, PSA, and PCSK9 levels, which can be prevented by daily oral PS treatment. PS-treated mice show reduced cholesterol, LDL-C, PCSK9, and PSA levels. These findings suggest that PS is a potential lead for suppressing mCRPC recurrence by targeting the PCSK9-LDLR axis.