Article
Multidisciplinary Sciences
Jaqueline Loaeza-Loaeza, Angel Josue Cerecedo-Castillo, Hugo Alberto Rodriguez-Ruiz, Yaneth Castro-Coronel, Oscar Del Moral-Hernandez, Felix Recillas-Targa, Daniel Hernandez-Sotelo
Summary: DNA methylation is an important epigenetic modification that regulates gene expression in mammalian cells. Abnormal DNA methylation in gene promoters is common in human cancer. DNMT3B is a methyltransferase that is enhanced in several primary tumors. However, the mechanism by which de novo methylation is established in genes related to cancer is not well understood.
SCIENTIFIC REPORTS
(2022)
Article
Plant Sciences
Lijun Li, Wenjie You, Xuewen Wang, Yulian Zou, Hong Yao, Hailin Lan, Xinhua Lin, Qiuyu Zhang, Bing Chen
Summary: The study found that the total biflavonoids extract from Selaginella doederleinii (TBESD) and a flavone monomer called Delicaflavone have favorable anti-tumor activity and can restore anti-tumor immune response. TBESD regulates the tumor microenvironment by increasing functional T cells and M1 phenotype TAMs, and decreasing M2 phenotype TAMs, monocytic-MDSCs, and regulatory T cells, thus inhibiting tumor growth.
Article
Oncology
Juan Rodrigo Patino-Mercau, Carlos Balinas-Gavira, Alvaro Andrades, Maria S. Benitez-Cantos, Ana Ercegovic Rot, Maria Isabel Rodriguez, Juan Carlos Alvarez-Perez, Marta Cuadros, Pedro P. Medina
Summary: Recent sequencing studies have shown that SWI/SNF complexes are frequently altered in solid tumors, but their role in acute myeloid leukemia (AML) is not well understood. This study focuses on the role of the BCL7A subunit in AML, which is recurrently mutated in lymphomas. The findings suggest that BCL7A is silenced by promoter hypermethylation in AML and its restoration suppresses tumor growth in AML cell lines and xenograft models.
BIOMARKER RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Yang Li, Min Liu, Shuting Yang, Ashley M. Fuller, T. S. Karin Eisinger-Mathason, Shuying Yang
Summary: This study identifies RGS12 as a novel tumor suppressor in osteosarcoma through inhibiting the YAP-TEAD1-Ezrin signaling pathway and provides evidence that targeting RGS12 may be a therapeutic strategy for osteosarcoma.
Article
Immunology
Juanjuan Ye, Futoshi Suizu, Keiko Yamakawa, Yuri Mukai, Motohiko Kato, Hiroyuki Yoneyama, Naohisa Yahagi, Yoko Matsuda
Summary: Limited infiltration of T cells in pancreatic ductal adenocarcinoma (PDAC) is a challenge for immunotherapy. In this study, we found that silencing carbohydrate sulfotransferase 15 (CHST15) suppressed tumor growth in a T-cell-dependent manner in a mice model of PDAC. Silencing CHST15 unexpectedly expanded T cells in tumor draining lymph nodes (TDLN), leading to increased accumulation of proliferating CD4(+) and CD8(+) T cells as well as granzyme B+ CD8(+) T cells in the tumor. Our findings demonstrate a novel immunotherapeutic potential of targeting CHST15 in PDAC by reactivating T cells in immune suppressive TDLN.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Canan Guvenc, Fien Neckebroeck, Asier Antoranz, Marjan Garmyn, Joost van den Oord, Francesca Maria Bosisio
Summary: Loss-of-function events in tumor suppressor genes, particularly through epigenetic alterations like promoter CpG-island hypermethylation, contribute to the development and progression of cutaneous malignant melanoma. This study identified 24 bona fide tumor suppressor genes affected by promoter CpG-island hypermethylation in CMM, outlining their functional roles in processes such as cell proliferation, apoptosis, growth, senescence, angiogenesis, migration, invasion, and metastasis. These findings provide further insight into the impact of tumor suppressor genes on the progression of cutaneous malignant melanoma.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Xiaochong Deng, Danrong Ye, Kaiyao Hua, Hongming Song, Qifeng Luo, Amik Munankarmy, Diya Liu, Baian Zhou, Wenfang Zheng, Xiqian Zhou, Changle Ji, Xuehui Wang, Yunhe Yu, Lin Fang
Summary: The long noncoding RNA MIR22 host gene (MIR22HG) was found to be lower in breast cancer tissues and mainly located in the cytoplasm. It acts as a miR-629-5p sponge, stabilizing the expression of large tumor suppressor 2 (LATS2) to inhibit the proliferation and migration of breast cancer cells through the miR-629-5p/LATS2 pathway.
CELL DEATH & DISEASE
(2021)
Review
Biochemistry & Molecular Biology
Da Young Lee, Jung Nyeo Chun, Minsoo Cho, Insuk So, Ju-Hong Jeon
Summary: E2F8 is a multifaceted transcription factor that is involved in various aspects of cancer development and progression. It has the ability to promote cancer cell proliferation and survival while also exhibiting tumor-suppressing activity. This review highlights the recent progress in understanding the role of E2F8 in human cancers and its implications for developing therapeutic strategies.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2023)
Article
Cell Biology
Hanhui Yao, Delong Ren, Yichun Wang, Liang Wu, Yang Wu, Wei Wang, Qidong Li, Lianxin Liu
Summary: This study found that KCTD9 is commonly downregulated in CRC tissues and its expression is negatively correlated with the clinical stage of CRC. Functional analyses revealed that KCTD9 overexpression inhibits CRC cell proliferation and metastasis, while KCTD9 knockdown promotes CRC cell proliferation and metastasis. Mechanistically, KCTD9 affects the degradation of beta-catenin, inhibiting the Wnt signaling pathway.
CELL DEATH & DISEASE
(2022)
Article
Oncology
Yousef M. Hawsawi, Anwar Shams, Abdulrahman Theyab, Wed A. Abdali, Nahed A. Hussien, Hanan E. Alatwi, Othman R. Alzahrani, Atif Abdulwahab A. Oyouni, Ahmad O. Babalghith, Mousa Alreshidi
Summary: This article reviews the spectrum of full-length BARD1 genes and their different isoforms, highlighting their anticipated associated risk. Additionally, the study emphasizes the role of BARD1 as an oncogene in breast cancer patients and its potential uses as a prognostic/diagnostic biomarker and therapeutic target for cancer susceptibility testing and treatment.
Article
Oncology
Gangqiang Ding, Yanli Zeng, Dongqiang Yang, Can Zhang, Chongshan Mao, Erhui Xiao, Yi Kang, Jia Shang
Summary: The study investigated the regulatory mechanism of DDX11-AS1-mediated miR-34a-3p/TRAF5 axis in hepatocellular carcinoma (HCC) cells. Results showed that downregulating DDX11-AS1 or upregulating miR-34a-3p inhibited HCC cell growth via elevation of TRAF5. Silencing TRAF5 or elevating miR-34a-3p expression mitigated the promotion of tumor growth by upregulated DDX11-AS1 in HCC cells. This research provides insights for potential early diagnostic markers for HCC patients.
CANCER CELL INTERNATIONAL
(2021)
Article
Multidisciplinary Sciences
Xinmiao Zhang, Angelica Rodriguez-Nino, Diego O. Pastene, Prama Pallavi, Jacob van den Born, Stephan J. L. Bakker, Bernhard K. Kraemer, Benito A. Yard
Summary: Research has shown that MGO treatment induces DNA damage and p53 activation in HUVECs, resulting in modulation of downstream pathways like mTORC1. Co-treatment with carnosine does not counteract the effects driven by MGO.
SCIENTIFIC REPORTS
(2021)
Article
Cell Biology
Feng Zhang, Tao Su, Meifang Xiao
Summary: This study investigated the function of circMETTL3/miR-107/PER3 in colorectal cancer (CRC). The findings suggest that circMETTL3, transcriptionally activated by RUNX3, acts as a sponge for miR-107 to regulate PER3 signaling, thereby inhibiting CRC cell proliferation and invasion and restraining tumor growth and metastasis.
CELL DEATH & DISEASE
(2022)
Article
Medicine, Research & Experimental
Cheng-Huang Shen, Jin-Yi Wu, Shou-Chieh Wang, Chi-Hung Wang, Chen-Tai Hong, Pei-Yu Liu, Sin-Rong Wu, Yi-Wen Liu
Summary: Glutathione S-transferases (GSTs) play an important role in metabolism and detoxification of various substances. A study found that GSTM2 gene expression is lower in advanced stages of bladder urothelial carcinoma, and overexpression of GSTM2 inhibits invasion, migration, and tumor formation of bladder cancer cells. The study also identified an SP1 site and several phytochemicals that can affect GSTM2 expression, with berberrubine and resveratrol being the most effective. Furthermore, it was found that a DNA methylation inhibitor and berberrubine can influence the methylation level of the GSTM2 gene.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Article
Pharmacology & Pharmacy
Priscilla Natalia, Julia Zwirchmayr, Ieva Rudzionyte, Alexandra Pulsinger, Johannes M. Breuss, Pavel Uhrin, Judith M. Rollinger, Rainer de Martin
Summary: Based on scientific research and traditional use, this study investigated the anti-inflammatory potential of red sandalwood in IL-1 stimulated endothelial cells. The results showed that red sandalwood extract can suppress the induction of molecules that mediate leukocyte adhesion to the endothelium, while stimulating the activation of the JNK signaling pathway. Gene expression profiling revealed that red sandalwood extract selectively inhibits certain IL-1 induced genes and stimulates the expression of negative regulatory genes.
FRONTIERS IN PHARMACOLOGY
(2022)
Review
Pharmacology & Pharmacy
Jose L. Medina-Franco, Edgar Lopez-Lopez, Emma Andrade, Lena Ruiz-Azuara, Angelo Frei, Davy Guan, Johannes Zuegg, Mark A. T. Blaskovich
Summary: Metallodrug discovery has made significant progress, but there is currently no dedicated public compound database. Establishing a metallodrug compound database would greatly facilitate the discovery and development of metallodrugs.
DRUG DISCOVERY TODAY
(2022)
Review
Pharmacology & Pharmacy
Edgar Lopez-Lopez, Eli Fernandez-de Gortari, Jose L. Medina-Franco
Summary: Studying structure-inactivity relationships is crucial for understanding biological activity, but the lack of inactivity data limits the development and application of predictive models. The scientific community should disclose and analyze high-confidence activity data considering both 'active' and 'inactive' compounds.
DRUG DISCOVERY TODAY
(2022)
Review
Pharmacology & Pharmacy
Fernanda Saldivar-Gonzalez, Jose L. Medina-Franco
Summary: This article reviews the current state of chemical space in drug design and discovery, discussing advances in efficient navigation and assessment of chemical space diversity, as well as highlighting recent methods for generating visual representations of chemical space.
EXPERT OPINION ON DRUG DISCOVERY
(2022)
Article
Biochemistry & Molecular Biology
Jose L. Medina-Franco, Edgar Lopez-Lopez, Liliam P. Martinez-Fernandez
Summary: This study reports two quinazoline-based derivatives with strong inhibitory activity against DNMT1, low affinity for DNMT3A, and no inhibition of DNMT3B. These compounds have low cell toxicity and effectively inhibit G9a.
Article
Chemistry, Medicinal
Edgar Lopez-Lopez, Carlos M. Cerda-Garcia-Rojas, Jose L. Medina-Franco
Summary: Modification of the tubulin-microtubule system has led to effective strategies for cancer treatment. However, many inhibitors of this system are based on limited structural innovation. This study aims to develop a screening protocol for natural products to identify new potential inhibitors of the tubulin-microtubule system.
MOLECULAR INFORMATICS
(2023)
Article
Oncology
Sikander Ailawadhi, Ricardo D. Parrondo, Navnita Dutta, Bing Han, Gina Ciccio, Yesesri Cherukuri, Victoria R. Alegria, Betsy R. LaPlant, Vivek Roy, Taimur Sher, Brett Edwards, Stephanie Lanier, Alak Manna, Keisha Heslop, Thomas Caulfield, Emir Maldosevic, Peter Storz, Rami Manochakian, Yan Asmann, Asher A. Chanan-Khan, Aneel Paulus
Summary: Bcl-2 family proteins play a crucial role in myeloma cell survival and are potential therapeutic targets. The combination of AT-101, lenalidomide, and dexamethasone (ARd regimen) demonstrates promising efficacy and safety in relapsed/refractory multiple myeloma patients, with positive effects on tumor burden reduction and immune cell modulation.
Article
Biochemistry & Molecular Biology
Edgar Lopez-Lopez, Jose L. Medina-Franco
Summary: Drug-induced liver injury (DILI) is a major obstacle in drug development and approval, with animal models, liver function tests, and chemical properties being crucial for understanding and preventing DILI events. This study implements data fusion to analyze DILI events by considering different criteria simultaneously, highlighting the importance of in vitro and chemical data analysis for improving our understanding of DILI.
Article
Biochemistry & Molecular Biology
Seth Osei Asiedu, Yash Gupta, Vlad Nicolaescu, Haley Gula, Thomas R. Caulfield, Ravi Durvasula, Prakasha Kempaiah, Samuel K. Kwofie, Michael D. Wilson
Summary: We previously demonstrated that Mycolactone (MLN), a toxin produced by Mycobacterium ulcerans, binds strongly to Munc18b and other proteins, potentially inhibiting degranulation and exocytosis. In this study, we investigated MLN's effects on endocytosis and found that it strongly binds to the N-terminal of the clathrin protein and a novel SARS-CoV-2 fusion protein.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Medicinal
Timothy B. Dunn, Edgar Lopez-Lopez, Taewon David Kim, Jose L. Medina-Franco, Ramon Alain Miranda-Quintana
Summary: "Understanding structure-activity landscapes" emphasizes the importance of the relationship between molecular structure and activity in drug discovery, and highlights the impact of activity cliffs on design and prediction. This study aims to use n-ary indices and the medoid algorithm to rapidly and efficiently quantify the structure-activity landscapes of large compound data sets, and explore the optimal correlations between similarity measures and structure-activity rankings. The applicability of these methods is demonstrated by analyzing 10 compound data sets with pharmaceutical relevance using different fingerprints, similarity indices, and coincidence thresholds.
MOLECULAR INFORMATICS
(2023)
Article
Biochemistry & Molecular Biology
Kenneth Lopez-Perez, Edgar Lopez-Lopez, Jose L. Medina-Franco, Ramon Alain Miranda-Quintana
Summary: Visualization of chemical space is crucial in various aspects of chemistry, such as compound library design and exploring structure-property relationships. ChemMaps is a visualization methodology that approximates compound distribution in large datasets based on satellite compounds with a similar mapping. Extended similarity indices are proposed to identify relevant regions and reduce high-dimensional data in describing a library's chemical space.
Review
Biochemistry & Molecular Biology
Cesar A. Zaa, alvaro J. Marcelo, Zhiqiang An, Jose L. Medina-Franco, Marco A. Velasco-Velazquez
Summary: Anthocyanins, a type of flavonoid, possess potent antioxidant properties and can penetrate the blood-brain barrier, exhibiting neuroprotective effects. Including anthocyanin-rich foods in the diet has been shown to lower the risk of neurodegenerative diseases, as their antioxidant, anti-inflammatory, and anti-apoptotic properties contribute to neuroprotection, particularly in Alzheimer's and Parkinson's diseases.
Article
Chemistry, Multidisciplinary
Raziel Cedillo-Gonzalez, Jose L. Medina-Franco
Summary: This study explores, characterizes, and analyzes the chemical space of 409 G9a inhibitors reported in a large public database. It quantifies the structural diversity of G9a inhibitors and compares them with commercial libraries focused on epigenetic targets. The findings will contribute to the development of predictive models for identifying G9a inhibitors and highlight the importance of screening commercial libraries to expand the relevant chemical space.
Article
Chemistry, Medicinal
Alejandro Gomez-Garcia, Daniel A. Acuna Jimenez, William J. Zamora, Haruna L. Barazorda-Ccahuana, Miguel A. Chavez-Fumagalli, Marilia Valli, Adriano D. Andricopulo, Vanderlan da S. Bolzani, Dionisio A. Olmedo, Pablo N. Solis, Marvin J. Nunez, Johny R. Rodriguez Perez, Hoover A. Valencia Sanchez, Hector F. Cortes Hernandez, Jose L. Medina-Franco
Summary: The Latin American Natural Products Database (LANaPDB) is a public compound collection that gathers chemical information of natural products from various databases in Latin America. The current version includes chemical structures from six countries, with terpenoids, phenylpropanoids, and alkaloids being the most abundant compounds. LANaPDB covers a wide chemical space and many compounds exhibit drug-like properties.
Article
Chemistry, Multidisciplinary
Edgar Lopez-Lopez, Oscar Robles, Fabien Plisson, Jose L. Medina-Franco
Summary: Peptide structure-activity/property relationship (P-SA/PR) studies aim to understand how the structural variations of peptides influence their biological activities and other functional properties, accelerating the rational design and optimization of peptide-based drugs, biomaterials, or diagnostic agents. This study used the MAP4 fingerprint to analyze the structure-activity relationship of 223 antimicrobial peptides against methicillin-resistant Staphylococcus aureus (MRSA), identifying critical residues and structural motifs that play a crucial role in the anti-MRSA activity of the peptides.
Review
Chemistry, Multidisciplinary
Conrad V. Simoben, Smith B. Babiaka, Aurelien F. A. Moumbock, Cyril T. Namba-Nzanguim, Donatus Bekindaka Eni, Jose L. Medina-Franco, Stefan Guenther, Fidele Ntie-Kang, Wolfgang Sippl
Summary: The use of traditional medicine has a long history and is still relied upon by many, especially in developing or underprivileged communities. In silico-based methods have played a crucial role in drug discovery, particularly in identifying natural product-based candidates. However, there are challenges in identifying and proposing novel natural product-based hits.