Review
Immunology
Ebru Aydin, Sebastian Faehling, Mariam Saleh, Laura Llao Cid, Martina Seiffert, Philipp M. Roessner
Summary: PI3K pathway plays a crucial role in cell growth and malignant transformation, with its hyperactivation being a hallmark of cancer. Inhibiting PI3K not only affects cancer cells but also impacts the tumor microenvironment and immune cell function. Understanding the effects of PI3K inhibition on the tumor microenvironment in CLL can lead to improved drug development and novel combinatory treatment strategies.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Natasha M. Setiabakti, Pia Larsson, Justin R. Hamilton
Summary: Understanding the role of phosphoinositide 3-kinases (PI3Ks) in platelet function and thrombus formation is crucial for the development of therapeutic drugs for thrombotic cardiovascular diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Allergy
Jessica Oh, Elizabeth Garabedian, Ramsay Fuleihan, Charlotte Cunningham-Rundles
Summary: Activated phosphoinositide 3-kinase delta syndrome is a combined primary immunodeficiency characterized by various manifestations such as respiratory infections, lymphadenopathy, and developmental delay. Clinical features differ between PIK3CD and PIK3R1 patients, with a higher frequency of asthma observed in the PIK3CD cohort.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE
(2021)
Article
Plant Sciences
Leila Kooshki, Seyede Nazanin Zarneshan, Sajad Fakhri, Seyed Zachariah Moradi, Javier Echeverria
Summary: Neurodegenerative diseases (NDDs) are characterized by progressive neuronal dysfunctionality. Conventional drugs have failed to attenuate the complications of NDDs. Polyphenols and alkaloids show beneficial pharmacological effects against NDDs by targeting the JAK/STAT and IRS/PI3K signaling pathways and their interconnected mediators.
Review
Chemistry, Medicinal
Jingyu Zhu, Kan Li, Li Yu, Yun Chen, Yanfei Cai, Jian Jin, Tingjun Hou
Summary: Phosphatidylinositol 3-kinase gamma (PI3Kγ) is considered a promising drug target for various diseases, with the importance of isoform selectivity in development highlighted; this review provides an overview of the structural features influencing selectivity, discusses the structure-activity relationship of existing inhibitors, and summarizes experimental and computational techniques for inhibitor identification.
MEDICINAL RESEARCH REVIEWS
(2021)
Article
Biochemistry & Molecular Biology
Li-Fu Li, Chung-Chieh Yu, Chih-Yu Huang, Huang-Pin Wu, Chien-Ming Chu, Ping-Chi Liu, Yung-Yang Liu
Summary: Mechanical ventilation (MV) used in patients with acute lung injury (ALI) induces lung inflammation and causes epithelial-mesenchymal transition (EMT). We hypothesized that MV with or without bleomycin treatment would increase EMT through the PI3K-gamma pathway. Our data suggest that MV augmented EMT after bleomycin-induced ALI, partially through the PI3K-gamma pathway.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Daniel Da Eira, Shailee Jani, Mateja Stefanovic, Rolando B. Ceddia
Summary: The purpose of this study was to determine the effects of the ketogenic diet on weight reduction and fat burning by examining the energy-dissipating pathways in brown adipose tissue (BAT) and white adipose tissue (WAT). The results showed that the ketogenic diet preserved insulin sensitivity and lipolytic capacity in WAT, and increased energy-dissipating pathways in BAT, but did not prevent an increase in adiposity.
JOURNAL OF NUTRITIONAL BIOCHEMISTRY
(2023)
Article
Physiology
Yui Shibayama, Chantal Alkhoury, Ivan Nemazanyy, Nathaniel Henneman, Nicolas Cagnard, Muriel Girard, Tatsuya Atsumi, Ganna Panasyuk
Summary: Class 3 PI3K is crucial for corticosterone metabolism and GR transcriptional activity in the liver.
Review
Biochemistry & Molecular Biology
Peter K. Vogt, Jonathan R. Hart, Su Yang, Qingtong Zhou, Dehua Yang, Ming-Wei Wang
Summary: Recent cryo-EM investigations have analyzed various structural conformations and functional states of PI3K, specifically its catalytic and regulatory subunits. High resolution structures of unliganded and BYL-719-bound PI3K have been obtained, providing insights into the flexible domains of the regulatory subunit. Mutations in the helical and kinase domains of the catalytic subunit have also been studied, revealing mutant-specific features related to enzymatic and signaling activities.
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER
(2023)
Article
Multidisciplinary Sciences
Qian Wang, Chenqi Tao, Abdul Hannan, Sungtae Yoon, Xuanyu Min, John Peregrin, Xiuxia Qu, Hongge Li, Honglian Yu, Jean Zhao, Xin Zhang
Summary: The patterning of epithelial buds in lacrimal gland development is determined by the interplay between PI3K, Ras, and ERK signaling pathways. PI3K is activated by both IGF and FGF signaling, and also promotes ERK signaling through direct interaction with Ras. Inhibition of EGF signaling is essential for induction of lacrimal gland buds, and the cross-talk among FGF, IGF, and EGF signaling is mediated by PI3K, MAPK, and mTOR.
Article
Cell Biology
Manoj K. Rathinaswamy, Meredith L. Jenkins, Benjamin R. Duewell, Xuxiao Zhang, Noah J. Harris, John T. Evans, Jordan T. B. Stariha, Udit Dalwadi, Kaelin D. Fleming, Harish Ranga-Prasad, Calvin K. Yip, Roger L. Williams, Scott D. Hansen, John E. Burke
Summary: This study investigates the activation mechanisms of phosphoinositide 3-kinase (PI3Ky) in immune cells. Using various experimental methods, the researchers identified molecular differences between the p110y-p84 and p110y-p101 complexes, which explain their differential membrane recruitment and activation by Ras and GPCRs. The findings provide key insights into the molecular basis of PI3Ky complex activation.
Article
Pharmacology & Pharmacy
Ava Safaroghli-Azar, Mohammad-Javad Sanaei, Atieh Pourbagheri-Sigaroodi, Davood Bashash
Summary: Lipid signaling refers to the biological process in which a lipid messenger binds to a protein target, converting its effects to specific cellular responses. The family of phosphoinositide 3-kinase (PI3K) plays a crucial role in this pathway, affecting various aspects of cellular biology such as cell survival, proliferation, migration, endocytosis, intracellular trafficking, metabolism, and autophagy. Different classes of PI3Ks have been identified in yeast and mammals, with class I PI3Ks being extensively studied in cancer biology. Abnormal activation of class I PI3Ks has been implicated in human tumors, particularly through activating mutations in the PIK3CA gene. Class II and III PI3Ks are involved in regulating vesicle trafficking and autophagy processes. This review aims to discuss the latest research findings on PI3Ks-mediated cell biological processes and explore the mechanisms by which different types of phosphoinositides derived from PI3Ks act.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Ee-Soo Lee, Tingqing Goo, Raj Kamal Srivastava, Assim Shabbir, Carlos F. Ibanez
Summary: Adipocyte hyperplasia and hypertrophy are regulated by different activin receptors, with ALK7 promoting adipocyte hypertrophy and ALK4 suppressing differentiation and promoting proliferation. ALK4 expression increases in response to nutrient overload and is associated with adipose tissue expansion during obesity. Mechanistically, ALK4 signaling suppresses the expression of CEBP alpha and PPAR gamma, leading to inhibition of adipocyte differentiation.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Alessandra Gentile, Nunzia Magnacca, Rita Matteis, Maria Moreno, Federica Cioffi, Antonia Giacco, Antonia Lanni, Pieter Lange, Rosalba Senese, Fernando Goglia, Elena Silvestri, Assunta Lombardi
Summary: This study investigated the physiological role of uncoupling protein 3 (UCP3) in white adipose tissue (WAT). The absence of UCP3 was found to impair the ability of WAT to store triglycerides, reduce oxidative capacity, decrease response to insulin, increase inflammation, and alter adipokine production. These findings highlight the importance of UCP3 in regulating the metabolic functionality of WAT and provide insights into the association between metabolic disorders and low UCP3 levels.
Article
Biotechnology & Applied Microbiology
Xijing Zhuang, Feng Gao, Lei Shi, Wei Liu, Wenjun Wang, Xuezhi He, Yang Gao
Summary: The study revealed that miR-146b-3p inhibits the proliferation, migration, and phenotype switch of VSMCs induced by PDGF-BB through targeting the PIK3CG pathway. This suggests that miR-146b-3p/PIK3CG could be a potential target for the treatment of atherosclerosis.
Article
Oncology
Iacopo Gesmundo, Laura Di Blasio, Dana Banfi, Tania Villanova, Alessandro Fanciulli, Enrica Favaro, Giacomo Gamba, Chiara Musuraca, Ida Rapa, Marco Volante, Stefania Munegato, Mauro Papotti, Paolo Gontero, Luca B. Primo, Ezio Ghigo, Riccarda Granata
Article
Endocrinology & Metabolism
Mari C. Vazquez-Borrego, Antonio C. Fuentes-Fayos, Aura D. Herrera-Martinez, Eva Venegas-Moreno, Fernando L-Lopez, Alessandro Fanciulli, Paloma Moreno-Moreno, Maria R. Alhambra-Exposito, Ana Barrera-Martin, Elena Dios, Cristobal Blanco-Acevedo, Juan Solivera, Riccarda Granata, Rhonda D. Kineman, Manuel D. Gahete, Alfonso Soto-Moreno, Maria A. Galvez-Moreno, Justo P. Castano, Raul M. Luque
NEUROENDOCRINOLOGY
(2020)
Article
Multidisciplinary Sciences
Lucia Recinella, Annalisa Chiavaroli, Giustino Orlando, Claudio Ferrante, Guya Diletta Marconi, Iacopo Gesmundo, Riccarda Granata, Renzhi Cai, Wei Sha, Andrew Schally, Luigi Brunetti, Sheila Leone
SCIENTIFIC REPORTS
(2020)
Correction
Multidisciplinary Sciences
Lucia Recinella, Annalisa Chiavaroli, Giustino Orlando, Claudio Ferrante, Guya Diletta Marconi, Iacopo Gesmundo, Riccarda Granata, Renzhi Cai, Wei Sha, Andrew V. Schally, Luigi Brunetti, Sheila Leone
SCIENTIFIC REPORTS
(2020)
Article
Endocrinology & Metabolism
Iacopo Gesmundo, Francesca Silvagno, Dana Banfi, Valentina Monica, Alessandro Fanciulli, Giacomo Gamba, Noemi Congiusta, Roberta Libener, Chiara Riganti, Ezio Ghigo, Riccarda Granata
FRONTIERS IN ENDOCRINOLOGY
(2020)
Article
Multidisciplinary Sciences
Lucia Recinella, Annalisa Chiavaroli, Valentina Di Valerio, Serena Veschi, Giustino Orlando, Claudio Ferrante, Iacopo Gesmundo, Riccarda Granata, Renzhi Cai, Wei Sha, Andrew Schally, Rossano Lattanzio, Luigi Brunetti, Sheila Leone
Summary: The newly synthesized GHRH antagonists MIA-690 and MR-409 have shown potent pharmacological effects in colon inflammation models, reducing sensitivity to nociceptive stimuli and decreasing the impact of acute and persistent inflammatory stimuli in mice.
SCIENTIFIC REPORTS
(2021)
Article
Medicine, Research & Experimental
Iacopo Gesmundo, Barbara Pardini, Eleonora Gargantini, Giacomo Gamba, Giovanni Birolo, Alessandro Fanciulli, Dana Banfi, Noemi Congiusta, Enrica Favaro, Maria Chiara Deregibus, Gabriele Togliatto, Gaia Zocaro, Maria Felice Brizzi, Raul M. Luque, Justo P. Castano, Maria Alessandra Bocchiotti, Simone Arolfo, Stefania Bruno, Rita Nano, Mario Morino, Lorenzo Piemonti, Huy Ong, Giuseppe Matullo, Juan M. Falcon-Perez, Ezio Ghigo, Giovanni Camussi, Riccarda Granata
Summary: Healthy adipocyte-derived EVs are beneficial for beta cell survival and function, while EVs from inflamed adipocytes cause beta cell death and dysfunction. Lean adipocyte-derived EVs have similar beneficial effects, whereas EVs from obese adipose tissue are harmful for beta cells. Differential expression of miRNAs and alterations in signaling pathways and gene expression in recipient beta cells were observed, suggesting that adipocyte-derived EVs may influence beta cell fate and function depending on the physiological and pathological state of adipose tissue.
Article
Biochemistry & Molecular Biology
Lucia Recinella, Annalisa Chiavaroli, Giustino Orlando, Claudio Ferrante, Serena Veschi, Alessandro Cama, Guya Diletta Marconi, Francesca Diomede, Iacopo Gesmundo, Riccarda Granata, Renzhi Cai, Wei Sha, Andrew V. Schally, Luigi Brunetti, Sheila Leone
Summary: Anxiety and depression are suggested to increase the risk for PTSD, while GHRH analogs may have therapeutic effects on mood disorders including PTSD by modulating inflammatory and oxidative status and affecting neural pathways.
MOLECULAR PSYCHIATRY
(2021)
Article
Biochemistry & Molecular Biology
Lucia Recinella, Annalisa Chiavaroli, Giustino Orlando, Claudio Ferrante, Iacopo Gesmundo, Riccarda Granata, Renzhi Cai, Wei Sha, Andrew Schally, Luigi Brunetti, Sheila Leone
Summary: The study found that MIA-690 increased food intake and body weight, while also elevating hypothalamic hormone and neurotransmitter levels and reducing serotonin levels. MR-409 had no significant effects on these markers.
Article
Oncology
Iacopo Gesmundo, Giuseppina Granato, Antonio C. Fuentes-Fayos, Clara Alvarez, Carlos Dieguez, Maria Chiara Zatelli, Noemi Congiusta, Dana Banfi, Nunzia Prencipe, Sheila Leone, Luigi Brunetti, Justo P. Castano, Raul M. Luque, Renzhi Cai, Wei Sha, Ezio Ghigo, Andrew Schally, Riccarda Granata
Summary: Various studies have shown that GHRH antagonists have inhibitory activities in experimental cancers, and this study found that MIA-602 and MIA-690 have anti-tumor effects in PAs by reducing cell growth and promoting cell death, suggesting they may be considered as new therapeutic options for the treatment of PAs.
Article
Medicine, Research & Experimental
Lucia Recinella, Annalisa Chiavaroli, Serena Veschi, Valentina Di Valerio, Rossano Lattanzio, Giustino Orlando, Claudio Ferrante, Iacopo Gesmundo, Riccarda Granata, Renzhi Cai, Wei Sha, Andrew V. Schally, Luigi Brunetti, Sheila Leone
Summary: The MIAMI class GHRH antagonist MIA-690 was shown to suppress the progression and growth of colorectal cancer (CRC) by reducing inflammatory and oxidative markers, modulating apoptotic and oncogenic pathways, and improving survival rates in mice. Further research is needed to explore the translation of these findings into clinical applications.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Article
Biochemistry & Molecular Biology
Loredana Bergandi, Umberto Lucia, Giulia Grisolia, Iris Chiara Salaroglio, Iacopo Gesmundo, Riccarda Granata, Romano Borchiellini, Antonio Ponzetto, Francesca Silvagno
Summary: The study developed a thermodynamic biochemical model to select the resonant frequency affecting different types of cancer, and demonstrated its effects in vitro. It investigated the cellular response to ELF electromagnetic wave in 3D cell culture models, finding that ELF-EMF can hinder cancer cell growth and alter metabolism.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Iacopo Gesmundo, Francesca Pedrolli, Nicoletta Vitale, Alessia Bertoldo, Giulia Orlando, Dana Banfi, Giuseppina Granato, Ramesh Kasarla, Federico Balzola, Silvia Deaglio, Renzhi Cai, Wei Sha, Mauro Papotti, Ezio Ghigo, Andrew Schally, Riccarda Granata
Summary: This study found that GHRH antagonist MIA-690 enhances the antitumor effect of cisplatin and pemetrexed in pleural mesothelioma by inhibiting proliferative and oncogenic pathways, as well as reducing inflammatory pathways and expression of oxidative, angiogenic, tumorigenic markers, and growth factors.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Marina Boido, Iacopo Gesmundo, Anna Caretto, Francesca Pedrolli, Roberta Schellino, Sheila Leone, Renzhi Cai, Wei Sha, Ezio Ghigo, Andrew V. Schally, Alessandro Vercelli, Riccarda Granata
Summary: The study shows that MR-409 has protective effects on SMN Delta 7 mice, indicating its potential as a promising drug for the treatment of SMA.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Review
Endocrinology & Metabolism
Andrew V. Schally, Xianyang Zhang, Renzhi Cai, Joshua M. Hare, Riccarda Granata, Manuela Bartoli
Article
Biochemistry & Molecular Biology
Chenchen Bian, Xiangtong Yuan, Caihong Zeng, Jian Sun, Gen Kaneko, Hong Ji
Summary: This study investigated the mechanism of docosahexaenoic acid (DHA)-induced apoptosis mediated by mitophagy, using grass carp as an animal model. The results showed that inhibition of mitophagy alleviated apoptosis and eliminated the inhibition of lipid accumulation induced by DHA. Mechanistically, DHA induced mitophagy by activating the PPAR gamma-LC3-BNIP3 pathway. Inhibition of PPAR gamma decreased autophagy-related gene expression and prevented BNIP3/NIX-mediated mitophagy-induced apoptosis, thereby alleviating the inhibition of lipid accumulation.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
(2024)
Article
Biochemistry & Molecular Biology
Venkatesan Ramya, Karuppiah Prakash Shyam, Arulanandu Angelmary, Balamuthu Kadalmani
Summary: This study reveals that Lauric acid (LA) exerts an epigenetic regulation and metabolic reprogramming on SH-SY5Y neuroblastoma cells through modulation of lncRNA HOTAIR, remodeling of chromatin H3K4 tri-methylation and regulation of glucose uptake by controlling NF-kappa B activation.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
(2024)
Article
Biochemistry & Molecular Biology
Sreelekshmi Sreekumar, Karyath Palliyath Gangaraj, Manikantan Syamala Kiran
Summary: This study investigates the intricate interplay between angiogenic regulation and the browning of white adipocytes. The findings reveal that concurrent activation of angiogenesis is necessary for inducing browning of white adipocytes. The study also highlights the role of Vascular endothelial growth factor (VEGF) in promoting angiogenesis and triggering the browning process through the activation of Estrogen receptor alpha (ER alpha) signaling pathway.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
(2024)
Article
Biochemistry & Molecular Biology
Zanxia Cao, Liling Zhao, Mingcui Chen, Zhihong Shi, Lei Liu
Summary: This study investigated the translocation process of cholesterol/calcitriol in bacterial membranes and their effects on membrane structure. Calcitriol facilitated water transport across the membrane, while cholesterol had the opposite effect. These findings contribute to a better understanding of the relationship between cholesterol/calcitriol concentrations, lipid bilayer structure, and water permeation.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
(2024)
Article
Biochemistry & Molecular Biology
Xiaozhen Guo, Jiawen Wang, Hualing Xu, Yangyang Wang, Yutang Cao, Yingquan Wen, Jiaqi Li, Yameng Liu, Kanglong Wang, Jue Wang, Xianchun Zhong, Chuying Sun, Yongxin Zhang, Jingyi Xu, Cuina Li, Pengxiang Mu, Lingyan Xu, Cen Xie
Summary: This study aims to investigate the role of the gut microbiota-bile acid axis in regulating the diurnal rhythms of metabolic homeostasis and assess the impact of obesity on them. The results show that high fat diet feeding and Leptin gene deficiency disrupt the rhythmic patterns of insulin sensitivity and serum total cholesterol levels. The study provides compelling evidence for the association between diurnal rhythm of insulin sensitivity and gut microbiota-bile acid axis, and elucidates the deleterious effects of obesity on gut microbiome-bile acid metabolism.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
(2024)
Article
Biochemistry & Molecular Biology
Giuseppe Pepe, Maria Cotugno, Federico Marracino, Luca Capocci, Ludovica Pizzati, Maurizio Forte, Rosita Stanzione, Pamela Scarselli, Alba Di Pardo, Sebastiano Sciarretta, Massimo Volpe, Speranza Rubattu, Vittorio Maglione
Summary: The study found that enzymes involved in sphingolipid metabolism show abnormal expression in the cardiac tissue of hypertensive rat models, which may be related to the susceptibility to cardiac damage.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
(2024)