Review
Cell Biology
Florian Hermans, Lara Hemeryck, Ivo Lambrichts, Annelies Bronckaers, Hugo Vankelecom
Summary: Tooth development relies on interactions between dental epithelium and mesenchyme, regulated by molecular pathways including Wnt, BMP, FGF, and Shh. These signaling modules intertwine during tooth development, outlining specific cell populations' development pathways.Recent studies have uncovered crucial Wnt-Shh interactions during odontogenesis, showing conservation in developing ectodermal appendages.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Cell Biology
Po-Hsuan Su, Rui-Lan Huang, Hung-Cheng Lai, Lin-Yu Chen, Yu-Chun Weng, Chih-Chien Wang, Chia-Chun Wu
Summary: NKX6-1 expression is associated with poor prognosis and malignant potential in LMS, enhancing tumor cell aggressiveness in vitro and promoting tumor growth in vivo. Overexpression and knockdown of NKX6-1 affect stem cell transcription factors and signaling pathways, including the NOTCH and Sonic hedgehog pathways. Inhibition of the SHH pathway may be a potential therapeutic strategy for LMS patients with high expression of NKX6-1.
JOURNAL OF BIOMEDICAL SCIENCE
(2021)
Review
Oncology
Soudeh Ghafouri-Fard, Tayyebeh Khoshbakht, Bashdar Mahmud Hussen, Mohammad Taheri, Majid Samsami
Summary: The Sonic Hedgehog (Shh) signaling pathway plays a crucial role in tumor formation, resistance to conventional therapies, tissue regeneration, and neurodegenerative disorders. Numerous non-coding RNAs (ncRNAs) and miRNAs have been identified to interact with the Shh pathway in both malignant and non-malignant conditions. This review summarizes the interactions between ncRNAs and Shh in various contexts.
CANCER CELL INTERNATIONAL
(2022)
Review
Biochemistry & Molecular Biology
Niraj Kumar Jha, Wei-Chih Chen, Sanjay Kumar, Rajni Dubey, Lung-Wen Tsai, Rohan Kar, Saurabh Kumar Jha, Piyush Kumar Gupta, Ankur Sharma, Rohit Gundamaraju, Kumud Pant, Shalini Mani, Sandeep Kumar Singh, Ricardo B. Maccioni, Tirtharaj Datta, Sachin Kumar Singh, Gaurav Gupta, Parteek Prasher, Kamal Dua, Abhijit Dey, Charu Sharma, Yasir Hayat Mughal, Janne Ruokolainen, Kavindra Kumar Kesari, Shreesh Ojha
Summary: Developmental signalling pathways play a central role in neuronal development and any aberration in these pathways can contribute towards neurological disorders. Extensive research has been conducted in the past decade on these pathways, revealing their potential as therapeutic targets for diseases.
Article
Multidisciplinary Sciences
Jun Sun, Dong Yeon Shin, Mark Eiseman, Alisha R. Yallowitz, Na Li, Sarfaraz Lalani, Zan Li, Michelle Cung, Seoyeon Bok, Shawon Debnath, Sofia Jenia Marquez, Tommy E. White, Abdul G. Khan, Ivo C. Lorenz, Jae-Hyuck Shim, Francis S. Lee, Ren Xu, Matthew B. Greenblatt
Summary: Slitrk5 acts as a negative regulator of hedgehog signaling in osteoblasts by enhancing osteoblast differentiation and inhibiting hedgehog signaling downstream targets. Mechanistically, Slitrk5 interacts with hedgehog ligands via its extracellular domain and with PTCH1 via its intracellular domain, ultimately modulating hedgehog signaling activity in the primary cilium.
NATURE COMMUNICATIONS
(2021)
Article
Biology
Victor Martinez-Heredia, Danielle Blackwell, Sujith Sebastian, Timothy Pearson, Gi Fay Mok, Laura Mincarelli, Charlotte Utting, Leighton Folkes, Ernst Poeschl, Iain Macaulay, Ulrike Mayer, Andrea Munsterberg
Summary: Skeletal muscle stem cells play a crucial role in tissue homeostasis and repair. This study demonstrates that primary cilia and the Talpid3 gene are essential for self-renewal of muscle stem cells and proper muscle regeneration.
COMMUNICATIONS BIOLOGY
(2023)
Article
Dermatology
Sophie Frech, Agnes Forsthuber, Ana Korosec, Katharina Lipp, Viktor Kozumov, Beate M. Lichtenberger
Summary: Patients with large scars, such as burn victims, face not only aesthetic challenges but also ongoing itching or pain that significantly reduces their quality of life. The regeneration of skin appendages, such as hair follicles, is a major objective for regenerative medicine as their lack limits scarless wound healing. In this study, the researchers found that Hedgehog signaling plays different roles in two distinct developmental lineages of dermal fibroblasts, promoting wound repair and inducing de novo hair follicle formation.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2022)
Article
Environmental Sciences
Ahmed G. Abd Elhameed, Manar G. Helal, Eman Said, Hatem A. Salem
Summary: The study demonstrated that saxagliptin can delay experimentally-induced hepatocellular carcinoma progression by improving liver function biomarkers and acting through the suppression of specific signaling pathways, enhancing tumor apoptosis, and suppressing proliferation.
ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY
(2021)
Review
Neurosciences
Asma Manzari-Tavakoli, Amirhesam Babajani, Mohammad Hadi Farjoo, Mostafa Hajinasrollah, Soheyl Bahrami, Hassan Niknejad
Summary: This article reviews the interactions between bone morphogenetic protein signaling and the key signaling pathways involved in neural differentiation, emphasizing the underlying molecular mechanisms. Understanding these interactions is crucial for the development of regenerative medicine and stem cell-based therapies.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2022)
Article
Gastroenterology & Hepatology
Emilia J. Orzechowska-Licari, Agnieszka B. Bialkowska, Vincent W. Yang
Summary: This study reveals that upon ionizing radiation-induced injury, intestinal epithelial cells increase SHH secretion, stimulating stromal cells to secrete WNT ligands, which leads to the activation of reserve intestinal stem cells (rISCs) (marked by BMI1) and subsequent epithelial regeneration.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2023)
Article
Oncology
Gui-Feng Su, Ze-Xiu Huang, Deng-Liang Huang, Peng-Xiao Chen, Yao Wang, Yi-Fei Wang
Summary: Cepharanthine was found to inhibit cellular proliferation and invasion, and promote apoptosis in liver cancer cells. Mechanistic investigations revealed that cepharanthine suppressed the Hedgehog/Gli1 signaling pathway and inhibited Wnt/beta-catenin signaling, suggesting cepharanthine as a potential therapy for refractory liver cancer and other Wnt/Hedgehog-driven cancers.
Review
Oncology
Lidia Gatto, Enrico Franceschi, Alicia Tosoni, Vincenzo Di Nunno, Stefania Bartolini, Alba Ariela Brandes
Summary: In the last decade, significant progress has been made in understanding the molecular biology of medulloblastoma, leading to the recognition of distinct molecular subgroups and the development of new clinical trials for updated treatment protocols. Medulloblastoma, previously considered a single disease, is now understood to be a heterogeneous tumor with different molecular subgroups that have varying gene expression profiles, pathogenetic driver alterations, clinical behaviors, and age at onset. Adult medulloblastoma, in particular, poses a challenge in neuro-oncology as there has been a lack of practice-changing clinical trials. The focus now is on translating the advances in cancer genomics into new molecularly targeted therapeutics to improve prognosis and treatment-related toxicities.
Article
Cell Biology
Rihao Qu, Khusali Gupta, Danni Dong, Yiqun Jiang, Boris Landa, Charles Saez, Gwendolyn Strickland, Jonathan Levinsohn, Pei-lun Weng, M. Mark Taketo, Yuval Kluger, Peggy Myung
Summary: This study designed a computational approach to resolve signals and cell behaviors in organogenesis, revealing the role of Wnt/β-catenin and SHH signaling gradients in cell proliferation and spatial patterning.
DEVELOPMENTAL CELL
(2022)
Article
Biology
Andrew M. Hamilton, Olga A. Balashova, Laura N. Borodinsky
Summary: Research indicates that Hedgehog (Hh) signaling may be a useful target for driving regeneration, and non-canonical mechanisms of Hh signaling are necessary for spinal cord and muscle regeneration.
Article
Medicine, General & Internal
Zeshaan N. Maan, Yuval Rinkevich, Janos Barrera, Kellen Chen, Dominic Henn, Deshka Foster, Clark Andrew Bonham, Jagannath Padmanabhan, Dharshan Sivaraj, Dominik Duscher, Michael Hu, Kelley Yan, Michael Januszyk, Michael T. Longaker, Irving L. Weissman, Geoffrey C. Gurtner
Summary: Hand injuries often lead to functional impairments, but fingertip regeneration is associated with hair follicle differentiation, Wnt, and hedgehog signaling pathways. Further research into these pathways may improve therapeutic outcomes for hand injuries in humans.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Monica L. Brown Lobbins, Andrzej T. Slominski, Karen A. Hasty, Sicheng Zhang, Duane D. Miller, Wei Li, Tae-Kang Kim, Zorica Janjetovic, Robert C. Tuckey, Imara-Safi O. Scott, Linda K. Myers, Arnold E. Postlethwaite
Summary: This study demonstrates that 17,20S(OH)(2)pD can suppress type I collagen synthesis and decrease the expression of fibrosis-related mediators, offering a potential noncalcemic secosteroidal therapeutic approach for treating systemic sclerosis and fibrosis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Pawel Brzeminski, Adrian Fabisiak, Radomir M. Slominski, Tae-Kang Kim, Zorica Janjetovic, Ewa Podgorska, Yuwei Song, Mohammad Saleem, Sivani B. Reddy, Shariq Qayyum, Yuhua Song, Robert C. Tuckey, Venkatram Atigadda, Anton M. Jetten, Rafal R. Sicinski, Chander Raman, Andrzej T. Slominski
Summary: This study established new routes for the chemical synthesis of vitamin D-3 and its hydroxy metabolites. The compounds showed similar properties in inhibiting cell proliferation and inducing cell differentiation, as well as effects on T-cell immune activity. They also interacted with nuclear receptors in a similar manner. The findings have important implications for studying the role of these compounds in the immune system and inflammatory diseases.
BIOORGANIC CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Yuwei Song, Radomir M. Slominski, Shariq Qayyum, Tae-Kang Kim, Zorica Janjetovic, Chander Raman, Robert C. Tuckey, Yuhua Song, Andrzej T. Slominski
Summary: This study used molecular simulation to investigate the interaction between vitamin D3 hydroxyderivatives and AhR. It was found that these derivatives can stimulate downstream target genes of AhR. Molecular dynamics simulations showed favorable binding of the derivatives to AhR and revealed potential mechanisms underlying their binding affinities.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2022)
Article
Biochemistry & Molecular Biology
Andrzej T. Slominski, Tae-Kang Kim, Radomir M. Slominski, Yuwei Song, Zorica Janjetovic, Ewa Podgorska, Sivani B. Reddy, Yuhua Song, Chander Raman, Edith K. Y. Tang, Adrian Fabisiak, Pawel Brzeminski, Rafal R. Sicinski, Venkatram Atigadda, Anton M. Jetten, Michael F. Holick, Robert C. Tuckey
Summary: CYP11A1 and CYP27A1 hydroxylate tachysterol(3), a photoproduct of previtamin D-3, producing 20S-hydroxytachysterol(3) and 25(OH)T-3, which are biologically active and interact with VDR, AhR, LXRs, and PPAR gamma. These metabolites inhibit cell proliferation and stimulate differentiation and anti-oxidative gene expression in keratinocytes and fibroblasts.
Article
Oncology
Andrzej T. Slominski, Anna A. Brozyna, Tae-Kang Kim, Mahmoud M. Elsayed, Zorica Janjetovic, Shariq Qayyum, Radomir M. Slominski, Allen S. W. Oak, Changzhao Li, Ewa Podgorska, Wei Li, Anton M. Jetten, Robert C. Tuckey, Edith K. Y. Tang, Craig Elmets, Mohammad Athar
Summary: Hydroxyderivatives of vitamin D3 have anti-cancer activities by acting on vitamin D receptor and retinoid-related orphan receptors, inhibiting cell proliferation and tumor formation.
INTERNATIONAL JOURNAL OF ONCOLOGY
(2022)
Article
Cell Biology
Allen S. W. Oak, George Cotsarelis
Summary: Adult mammals can regenerate hair follicles after wounding, which is similar to embryogenesis. The origin of stem cells and the role of mesenchymal cells and signaling pathways in wound-induced hair neogenesis are being uncovered. This discovery opens up the possibility of manipulating cell fate during wound healing to promote hair follicle formation.
COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY
(2023)
Article
Oncology
Ewelina Madej, Anna A. Brozyna, Agnieszka Adamczyk, Norbert Wronski, Agnieszka Harazin-Lechowska, Anna Muzyk, Krzysztof Makuch, Michal Markiewicz, Janusz Rys, Agnieszka Wolnicka-Glubisz
Summary: RIPK4 kinase has oncogenic functions in melanoma and shows high similarity to BRAF protein, making this kinase sensitive to the BRAF inhibitors vemurafenib and dabrafenib. BRAFi downregulates RIPK4 in both BRAF-mutated and wild-type cells. Although downregulation and upregulation of RIPK4 does not affect signal transduction through the BRAF/MEK/ERK pathway in melanoma, it can inhibit cell proliferation and the FAK/AKT pathway.
Article
Biochemistry & Molecular Biology
Robert C. Tuckey, Chloe Y. S. Cheng, Lei Li, Yuhan Jiang
Summary: Our study found that 25-hydroxyvitamin D3 (25(OH)D3) can exist in the human circulation in the sulfated form, and can be metabolized by vitamin D-metabolizing cytochromes P450 (CYPs). Specifically, CYP27A1 can convert vitamin D3 sulfate to 25(OH)D3 3-sulfate, while CYP11A1 can convert vitamin D3 sulfate to 20(OH)D3 3-sulfate, but at a lower rate.
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Warusavithana Gunawardena Manori De Silva, Bianca Yuko McCarthy, Jeremy Han, Chen Yang, Andrew J. A. Holland, Harvey Stern, Katie Marie Dixon, Edith Kai Yan Tang, Robert Charles Tuckey, Mark Stephen Rybchyn, Rebecca Sara Mason
Summary: In this study, it was found that the over-irradiation metabolite 24(OH)L-3 provided photoprotection against UV-induced DNA damage similar to that of 1,25(OH)(2)D-3. The mechanisms involved increased energy availability and DNA repair, as well as decreased reactive oxygen species.
Article
Veterinary Sciences
Dimitar Bakalov, Petar Iliev, Zafer Sabit, Radka Tafradjiiska-Hadjiolova, Georgeta Bocheva
Summary: This study aimed to examine the changes in behavior, cognition, and memory in rats with PTU-induced overt hypothyroidism and the effects of tryptophan treatment on this state. The results showed significant differences in the behavioral patterns of the hypothyroid rats, including reduced locomotor activity, rearing, and memory function, which were alleviated by treatment with 5-OH-TRP. These findings have important implications for further investigation of functional and structural changes in the hippocampus during a hypothyroid state and the effects of serotonin mediation on hypothyroid-associated depressive behavior.
VETERINARY SCIENCES
(2023)
Editorial Material
Dermatology
Andrzej T. Slominski, Robert C. Tuckey, Anton M. Jetten, Michael F. Holick
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Lei Li, Robert C. Tuckey
Summary: Vitamin D exists in two forms, D3 produced in the skin and D2 obtained from the diet. The enzyme CYP24A1 plays a crucial role in oxidizing and inactivating both forms of vitamin D, regulating their serum levels. This study aimed to clarify the pathways of oxidation for 25(OH)D2 and 1,25(OH)(2)D2 and compare their metabolism with their vitamin D3 counterparts.
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Dongxian Wu, Gareth Nealon, Yuchen Liu, Tae-Kang Kim, Andrzej T. Slominski, Robert C. Tuckey
Summary: Lumisterol2 (L2) is a photoproduct of UVB action on ergosterol, which is present in edible mushrooms and human skin. CYP27A1 efficiently metabolizes L2 to produce three major hydroxy-L2 products, while CYP11A1 has minimal effect on L2 metabolism. The major CYP27A1-derived hydroxy-L2 products have anti-proliferative activity on skin-cancer cell lines.
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY
(2023)
Article
Chemistry, Inorganic & Nuclear
Marzena Fandzloch, Tomasz Jedrzejewski, Joanna Wisniewska, Jerzy Sitkowski, Liliana Dobrzanska, Anna A. Brozyna, Sylwia Wrotek
Summary: Three ruthenium(i) complexes containing purine analogs were synthesized and characterized. They showed potential as photo-activated CO-releasing molecules and CO-based therapies. The impact of UV-induced modification on their anticancer properties was investigated.
DALTON TRANSACTIONS
(2022)
Meeting Abstract
Oncology
Andrzej T. Slominski, Ewa Podgorska, Tae-Kang Kim, Anna A. Brozyna, Zorica Janjetovic, Shariq Qayum, Guroji Purushotham, Mahmoud M. Elsayed, Allen S. W. Oak, Changzhao Li, Hunter C. Weeks, Radomir M. Slominski, Chander Raman, Jake Chen, Craig Elmets, Wei Li, Edith K. Y. Tang, Robert C. Tuckey, Anton M. Jetten, Mohammad Athar
ANTICANCER RESEARCH
(2022)