Article
Multidisciplinary Sciences
Takahiro Masaki, Makoto Habara, Yuki Sato, Takahiro Goshima, Keisuke Maeda, Shunsuke Hanaki, Midori Shimada
Summary: The study reveals that calcineurin regulates the stability and activity of ER-alpha in breast cancer cells by modulating its phosphorylation at Ser 294 and Ser 118 positions. The expression of the calcineurin A-alpha gene (PPP3CA) is associated with poor prognosis in ER-alpha-positive breast cancer patients, suggesting calcineurin as a promising target for therapies in ER-alpha-positive breast cancer.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Oncology
Lu Lu, Yi-Xin Jiang, Xiao-Xia Liu, Jin-Mei Jin, Wen-Jie Gu, Xin Luan, Ying-Yun Guan, Li-Jun Zhang
Summary: Colorectal cancer (CRC) is a major malignant tumor with limited efficacy of existing therapies, making it necessary to explore potential combination therapy to improve immunotherapy efficacy. GW4064, a FXR agonist, has been found to induce apoptosis, block cell cycle, and mediate immunogenic cell death (ICD) of CRC cells in vitro. However, it could not suppress CRC tumor growth in vivo. Further studies showed that GW4064 upregulated PD-L1 expression in CRC cells through activating FXR and MAPK signaling pathways. Combination therapy of PD-L1 immune checkpoint blockade with FXR agonist exhibited excellent anti-tumor effects and increased CD8(+) T cells infiltration, with 33% tumor bearing mice cured.
Article
Biochemistry & Molecular Biology
Elisa Rossini, Edoardo Giacopuzzi, Fabrizio Gangemi, Mariangela Tamburello, Deborah Cosentini, Andrea Abate, Marta Lagana, Alfredo Berruti, Salvatore Grisanti, Sandra Sigala
Summary: Mitotane is found to have estrogenic-like effects on the ER-alpha receptor. Through cell experiments and molecular simulations, it was demonstrated that mitotane binds directly to and activates ER-alpha.
Article
Biochemistry & Molecular Biology
Aoi Ikedo, Yuuki Imai
Summary: Estrogen deficiency impairs fracture healing by affecting the expression ratio of estrogen receptors, especially ERα, in callus during the process. The study clarified the significance of ERs during fracture healing using osteoblast-specific ER knockout mice, showing that ERα in osteocalcin-positive osteoblasts may contribute to the late stage of bone regeneration.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Medicine, Research & Experimental
Malay K. Sannigrahi, Pavithra Rajagopalan, Ling Lai, Xinyi Liu, Varun Sahu, Hiroshi Nakagawa, Jalal B. Jalaly, Robert M. Brody, Iain M. Morgan, Bradford E. Windle, Xiaowei Wang, Phyllis A. Gimotty, Daniel P. Kelly, Elizabeth A. White, Devraj Basu
Summary: Therapy with radiation plus cisplatin kills HPV+ oropharyngeal squamous cell carcinomas (OPSCCs) by increasing reactive oxygen species beyond cellular antioxidant capacity. However, this standard treatment fails for some patients, and this study explores the potential role of HPV oncoprotein levels in affecting mitochondrial metabolism and treatment resistance. The results show that higher levels of the HPV oncoprotein fl-E6 are associated with reduced oxidative phosphorylation, antioxidant capacity and therapy resistance. Ectopically expressing fl-E6 in models with low baseline levels further depletes mitochondrial mass, sensitizes to therapy, and represses the alpha pathway for mitochondrial biogenesis. Clinical data supports these findings, with tumors expressing lower levels of fl-E6 displaying higher p53 target gene expression and an activated PGC-1 alpha/ERR alpha pathway, as well as reduced patient survival. These findings suggest that low levels of the HPV oncoprotein E6 can negatively affect treatment response and patient survival, and highlight the importance of considering the E6- PGC-1 alpha/ERR alpha axis in predicting and targeting treatment resistance in OPSCC.
Article
Multidisciplinary Sciences
Kin H. Lau, Althea N. Waldhart, Holly Dykstra, Tracey Avequin, Ning Wu
Summary: Brown adipose tissue (BAT) has the ability to burn calories as heat, which is an attractive way to combat obesity. However, the transcriptional network resulting in the lipid synthesis to oxidation shift during thermogenesis is not completely understood.
Article
Obstetrics & Gynecology
Koki Shimura, Yosuke Tarumi, Maya Fujii, Kanae Ogawa, Eiko Maeda, Yukiko Tanaka, Hiroyuki Okimura, Hisashi Kataoka, Osamu Takaoka, Fumitake Ito, Akemi Koshiba, Khaleque N. Khan, Izumi Kusuki, Jo Kitawaki, Taisuke Mori
Summary: This study investigates the effects of a low-nutrient microenvironment on endometriosis. The results show that under the low-nutrient condition, stromal cells from ovarian endometrioma (OESCs) have higher proliferation and exhibit changes in gene and protein expression related to angiogenesis, inflammation, anti-apoptosis, and local estrogen production.
REPRODUCTIVE SCIENCES
(2023)
Article
Oncology
Lei Wang, Mengmeng Yang, Huihan Jin
Summary: The study demonstrated that PI3K/AKT phosphorylation enhances ERR alpha activity in NOZ cells by upregulating the expression levels of PGC-1 alpha and PGC-1 beta, promoting the invasion and proliferation of gallbladder cancer cells.
MOLECULAR MEDICINE REPORTS
(2021)
Article
Integrative & Complementary Medicine
Meng Hui, Wang Qi-yan, Li Ning, He Hao, Lu Wen-ji, Wang Qi-xin, Sun Xiao-qian, Jiao Shi-hong, Wang Yong, Tu Peng-fei
Summary: Danqi Tablet (DQT) has a cardioprotective effect on ischemic heart model rats, increasing ATP production in myocardial cells and inhibiting inflammation. It regulates energy metabolism through the AMPK/SIRT1-PGC-1 alpha pathway, suggesting a potential target for treating ischemic heart disease.
CHINESE JOURNAL OF INTEGRATIVE MEDICINE
(2021)
Review
Cell Biology
Youssef Siblini, Fares Namour, Abderrahim Oussalah, Jean-Louis Gueant, Celine Chery
Summary: Stem cells rely on methionine for maintenance and differentiation, with one-carbon metabolism playing a crucial role. Cultivating stem cells under methionine-restricted conditions decreases their stemness capacities and alters the expression of stem cell markers. Genes like SIRT1 and PGC-1 alpha/PPAR-alpha are important in regulating the metabolism of stem cells. Methionine restriction holds potential applications in regenerative medicine and cancer treatment.
Article
Cell Biology
Adele M. Musicant, Kshitij Parag-Sharma, Weida Gong, Monideepa Sengupta, Arindam Chatterjee, Erin C. Henry, Yi-Hsuan Tsai, Michele C. Hayward, Siddharth Sheth, Renee Betancourt, Trevor G. Hackman, Ricardo J. Padilla, Joel S. Parker, Jimena Giudice, Colin A. Flaveny, David N. Hayes, Antonio L. Amelio
Summary: Mucoepidermoid carcinoma (MEC) is a life-threatening salivary gland cancer primarily driven by a fusion protein composed of CRTC1 and MAML2. This study shows that the fusion protein C1/M2 induces activation of the PGC-1 alpha 4 splice variant, leading to regulation of the IGF-1 pathway and sensitivity to IGF-1R inhibition in MEC cells. These findings provide insights into potential precision therapy targets for MEC.
Article
Biochemistry & Molecular Biology
Andrew D. Huber, William C. Wright, Wenwei Lin, Kinjal Majumder, Jonathan A. Low, Jing Wu, Cameron D. Buchman, David J. Pintel, Taosheng Chen
Summary: This study found that mutating a single residue in the PXR receptor can convert the antagonist SPA70 into an agonist. Molecular dynamics simulations revealed that in certain cases, the action of SPA70 is similar to that of agonists, further elucidating the relationship between the structure and activity of the PXR receptor.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Article
Genetics & Heredity
Yuyou Yang, Naibo Feng, Li Liang, Rong Jiang, Yiming Pan, Nana Geng, Mengtian Fan, Xiaoli Li, Fengjin Guo
Summary: This study confirmed the important role of PGRN in regulating the estrogen signal, maintaining bone homeostasis. Our findings may provide a new strategy for the treatment of osteoporosis and maintaining bone homeostasis.
JOURNAL OF MOLECULAR MEDICINE-JMM
(2022)
Article
Biochemistry & Molecular Biology
Sugunadevi Sakkiah, Chandrabose Selvaraj, Wenjing Guo, Jie Liu, Weigong Ge, Tucker A. Patterson, Huixiao Hong
Summary: ERalpha is a ligand-dependent transcriptional factor, and this study used molecular docking, molecular dynamics simulations, and quantum mechanical calculations to elucidate the dynamic binding patterns of agonists and antagonists in ER alpha. The results showed that OHT binds ER alpha more tightly in the antagonist conformer, while E2 prefers the agonist conformer, which may have implications for drug development and risk assessment related to ER-mediated responses.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Hsuan-Miao Liu, Zi-Yu Chang, Ching-Wei Yang, Hen-Hong Chang, Tzung-Yan Lee
Summary: The FXR/beta Klotho/FGFs pathway plays a crucial role in maintaining the intestinal barrier and preventing colorectal cancer. Activation of FXR with GW4064 improves intestinal barrier dysfunction and inhibits colon carcinogenesis, while FXR knockout mice show disrupted intestinal microbial health and increased colon cancer markers.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Cell Biology
Sangita Chowdhury, Arun K. Trivedi
Summary: This article provides a comprehensive review on macrophages, including their origin, functional diversity, polarization, specialized markers, and their role as therapeutic targets in different diseases. It specifically discusses the tumor-associated macrophages (TAMs) and their role in tumor progression, as well as newly discovered markers that could be potential therapeutic targets. Understanding the diversity of macrophages is crucial for activating the immune system against diseases and overcoming immune resistance.
CELL BIOLOGY INTERNATIONAL
(2023)
Article
Biochemistry & Molecular Biology
Swati Srivastava, Shumaila Siddiqui, Sangita Chowdhury, Arun Kumar Trivedi
Summary: Dexamethasone treatment leads to an increase in glucocorticoid receptor (GR) protein levels in non-small cell lung cancer (NSCLC) cells through JNK activation. JNK phosphorylation precedes GR upregulation, and JNK-mediated GR stabilization affects its nuclear transcriptional functional activity in NSCLC cells. Increased levels of both JNK and GR contribute towards better prognosis of NSCLC patients.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Article
Cell Biology
Mukul Mishra, Anil Kumar Singh, Gatha Thacker, Vishal Upadhyay, Sabyasachi Sanyal, Arun Kumar Trivedi
Summary: ORM can induce megakaryocytic and myeloid differentiation in the K562 cell line. This induction is mediated by activation of ERK and induction of autophagy. Additionally, inhibition of caspases can mitigate megakaryocytic differentiation. These findings suggest that ORM has potential as an inducer of megakaryocytic differentiation.
CELL BIOLOGY INTERNATIONAL
(2023)
Review
Biochemistry & Molecular Biology
Swati Srivastava, Sanjay Kumar, Rohini Bhatt, Ravishankar Ramachandran, Arun K. Trivedi, Tapas K. Kundu
Summary: Acetylation is a key protein modification catalyzed by lysine acetyltransferases (KATs). KATs transfer acetyl groups to lysine residues in histones and non-histone proteins. KATs regulate biological processes and their aberrant activities may underlie human diseases.
JOURNAL OF BIOCHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Sangita Chowdhury, Anil Kumar Singh, Swati Srivastava, Vishal Upadhyay, Arppita Sethi, Shumaila Siddiqui, Arun Kumar Trivedi
Summary: In this study, it was found that E3 ubiquitin ligase AIP4 negatively regulates C/EBPa protein stability, leading to reduced adipogenesis. AIP4 overexpression inhibits lipid accumulation in 3T3-L1 preadipocytes, while AIP4 depletion promotes lipid accumulation even in the absence of differentiation-inducing media. AIP4 physically interacts with C/EBPa and promotes its ubiquitination, resulting in proteasomal degradation.
JOURNAL OF CELLULAR BIOCHEMISTRY
(2023)
Article
Neurosciences
Sangh Jyoti Singh, Ankit Tandon, Phoolmala, Tulika Srivastava, Nivedita Singh, Shweta Goyal, Smriti Priya, Rajnish Kumar Chaturvedi
Summary: This study found that bisphenol-A (BPA) negatively affects the proliferation and differentiation of neural stem cells, leading to neurological disorders during brain development. BPA impairs the ubiquitin-proteasome system (UPS) by reducing its activity in neural stem cells, resulting in disrupted neuronal differentiation. However, UPS activation with a bioactive triterpenoid 18 alpha-glycyrrhetinic acid (18 alpha GA) can alleviate BPA-induced neurotoxicity and provide neuroprotection.
MOLECULAR NEUROBIOLOGY
(2023)
Article
Endocrinology & Metabolism
Chirag Kulkarni, Shivani Sharma, Konica Porwal, Swati Rajput, Sreyanko Sadhukhan, Vaishnavi Singh, Akanksha Singh, Sanjana Baranwal, Saroj Kumar, Aboli Girme, Alka Raj Pandey, Suriya Pratap Singh, Koneni V. Sashidhara, Navin Kumar, Lal Hingorani, Naibedya Chattopadhyay
Summary: A study found that Coleus forskohlii root extract (CF) containing forskolin can activate adenylate cyclase (AC) and increase intracellular cyclic adenosine monophosphate (cAMP) levels in osteoblasts, protecting obese individuals against weight gain. Through a series of experiments and tests, researchers found that CFE can promote the maintenance of bone mass, bone strength, and bone material.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Medicine, Research & Experimental
Shaziya Khan, Desh Raj, Shikha Sahu, Anam Naseer, Nishakumari C. Singh, Sunaina Kumari, Sharmeen Ishteyaque, Jyotsna Sharma, Promila Lakra, Madhav N. Mugale, Arun Kumar Trivedi, Mrigank Srivastava, Tulika Chandra, Vivek Bhosale, Manoj Kumar Barthwal, Shashi Kumar Gupta, Kalyan Mitra, Aamir Nazir, Uday C. Ghoshal, Amit Lahiri
Summary: Altered mitochondrial function has been observed in ulcerative colitis patients, with reduced expression of CLUH. CLUH negatively regulates proinflammatory cytokine secretion and regulates DRP1 transcription. Knockdown of CLUH exacerbates disease pathology in a colitis mouse model.
Article
Biochemistry & Molecular Biology
Jijo Thomas, Vianni Chopra, Swati Rajput, Rajdeep Guha, Naibedya Chattopadhyay, Deepa Ghosh
Summary: Injectable hydrogels have been used for cartilage repair, but some of them have issues with rapid degradation and low mechanical strength. To address these challenges, a bioinspired double network hydrogel (BDNH) was developed, which exhibits temperature-dependent stiffening after implantation. The BDNH showed excellent cell viability, long time cell proliferation, and cartilage specific matrix production, making it a potential candidate for cartilage tissue engineering.
Article
Chemistry, Multidisciplinary
Himadri Shekar Roy, K. M. Neethu, Swati Rajput, Sreyanko Sadhukhan, Vijayendran Gowri, Arif Hassan Dar, Malika Monga, Navita Salaria, Rajdeep Guha, Naibedya Chattopadhyay, Govindasamy Jayamurugan, Deepa Ghosh
Summary: The excess nitric oxide (NO) produced in response to bacterial/proinflammatory stimuli is responsible for pathological conditions. Current approaches targeting excess NO production have been unsuccessful. Urea-functionalized push-pull chromophores with NO scavenging properties have shown therapeutic efficacy in modulating NO-mediated diseases and have potential for further research.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Biochemistry & Molecular Biology
Sri Vidya Dangudubiyyam, Bradley Bosse, Pankaj Yadav, Ruolin Song, Alissa Hofmann, Jay S. Mishra, Sathish Kumar
Summary: This study found that AT2R activation can improve maternal vascular dysfunction and blood flow caused by PFOS exposure, restoring normal fetal growth. This provides important preclinical evidence for the prevention or treatment of adverse maternal and fetal outcomes caused by PFOS.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Medicine, Research & Experimental
Kaveri R. Washimkar, Manendra Singh Tomar, Chirag Kulkarni, Shobhit Verma, Ashutosh Shrivastava, Naibedya Chattopadhyay, Madhav Nilakanth Mugale
Summary: This study elucidates the association of TGF-β1/Smad and Nrf2 signaling in the EMT and metabolic alterations associated with the etiology and progression of PF.
Article
Endocrinology & Metabolism
Subhashis Pal, Shivani Sharma, Konica Porwal, Mahesh C. Tiwari, Yasir A. Khan, Saroj Kumar, Navin Kumar, Naibedya Chattopadhyay
Summary: Vascular dysfunction contributes to osteopenia in hypertensive patients. The effect of anti-hypertensive medicines on bone mass is unclear, suggesting that reducing blood pressure alone is insufficient. PTX, a hemorheological drug, improves blood flow and has an osteogenic effect. This study shows the importance of vascular function and increased bone mass in improving bone health, providing a potential treatment option for osteoporosis in hypertensive patients.
CALCIFIED TISSUE INTERNATIONAL
(2023)
Review
Endocrinology & Metabolism
Somali Sanyal, Swati Rajput, Sreyanko Sadhukhan, Singh Rajender, Ambrish Mithal, Naibedya Chattopadhyay
Summary: This meta-analysis examines the impact of Runx2 T > C and osteocalcin HindIII polymorphisms on bone mineral density (BMD) in postmenopausal women. The findings suggest that the Runx2 T > C polymorphism is associated with decreased BMD in the lumbar spine, while the osteocalcin HindIII polymorphism is associated with increased BMD in the lumbar spine and femoral neck.
Review
Endocrinology & Metabolism
Sreyanko Sadhukhan, Shruti Sethi, Singh Rajender, Ambrish Mithal, Naibedya Chattopadhyay
Summary: This meta-analysis study provides the first definition of the pathophysiology of idiopathic osteoporosis (IOP), finding that it primarily leads to a decline in lumbar spine bone density compared to healthy controls, with no changes in bone turnover markers. Further research is needed to understand gender differences and the significance of altered hormone levels in this condition.