Article
Biochemistry & Molecular Biology
Noor Mustafa, Jone Mitxelena, Arantza Infante, Olatz Zenarruzabeitia, Ainhoa Eriz, Ainhoa Iglesias-Ara, Ana M. Zubiaga
Summary: Disruption of E2f2 in mice leads to T-cell hyperactivation and disproportionate cell cycle entry. However, E2f2(-/-) mice do not develop lymphoproliferative condition. We find that E2f2 plays an anti-apoptotic role through the Fas pathway in vitro and in vivo. Knockout of E2f2 in TCR-stimulated T cells results in overexpression of proapoptotic genes, enhanced apoptosis, and activated p53 pathway. However, E2f2-Fas/FasL signaling is p53-independent. E2f2 is recruited to Fas and FasL gene promoters to repress their expression. E2f2(-/-) mice are prone to immune-mediated liver injury due to aberrant lymphoid Fas/FasL activation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Yingcui Yang, Mingqing Zhang, Yongdan Zhang, Kebin Liu, Chunwan Lu
Summary: 5-Fluorouracil (5-FU) selectively kills myeloid-derived suppressor cells (MDSCs) and increases cytotoxic T lymphocyte activation, leading to enhanced antitumor immunity in colorectal cancer patients. The molecular mechanism underlying 5-FU's suppression of MDSCs involves the activation of the p53-Fas pathway, which upregulates Fas expression and increases MDSC sensitivity to apoptosis. 5-FU therapy effectively suppresses MDSC accumulation and promotes CTL tumor infiltration.
Review
Cell Biology
Meredith Gregory-Ksander, Ann Marshak-Rothstein
Summary: Fas ligand not only induces cell death, but also affects proinflammatory cytokine production, T cell activation, and cell motility; the distinct functions of mFasL and sFasL require further study.
JOURNAL OF LEUKOCYTE BIOLOGY
(2021)
Article
Immunology
Giovanna Flores-Mendoza, Noe Rodriguez-Rodriguez, Rosa M. Rubio, Iris K. Madera-Salcedo, Florencia Rosetti, Jose C. Crispin
Summary: The study revealed that Fas and FasL play an important role in the downregulation of CD8 cells induced by self-antigens, maintaining CD8 expression. The signaling of Fas/FasL is crucial for sustaining CD8 expression during repetitive antigen stimulation and encounters with self-antigens.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Anatomy & Morphology
Zhengguang Wang, Yongfang Tan, Fei Xu
Summary: This study aimed to investigate the effects of zonisamide (ZNS) on a degenerative cervical myelopathy (DCM) rat model and explore the potential mechanisms. The results showed that ZNS promoted motor recovery, reversed histopathological injury and cell apoptosis in DCM rats. Additionally, ZNS attenuated DCM injury through the regulation of Fas and FasL signaling. Therefore, this study provided a new theoretical approach for subsequent academic and clinical research on DCM injury.
Article
Pharmacology & Pharmacy
Vanessa Pereira, Juri Aparicio Arias, Amadeu Llebaria, Cyril Goudet
Summary: Neuropathic pain is a challenging condition to manage. In this study, the role of the amygdala in regulating neuropathic pain was investigated. The activation of mGlu4 receptors in the amygdala was found to alleviate sensory and depressive-like symptoms in a mouse model of neuropathy.
PHARMACOLOGICAL RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Carlos Alberto Castillo, Inmaculada Ballesteros-Yanez, David Agustin Leon-Navarro, Jose Luis Albasanz, Mairena Martin
Summary: The amyloid beta peptide plays a central role in Alzheimer's disease pathology. Exposure to A beta(25-35) in rat cortical neurons increased mGluR density and affinity, along with up-regulation of adenosine A(1)R and A(2A)R. The study highlights the possible involvement of metabotropic glutamate and adenosine receptors in the early events of AD physiopathology.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Neurosciences
Ananth Prasad Burada, Rajesh Vinnakota, Bertrand Lambolez, Ludovic Tricoire, Janesh Kumar
Summary: Enigmatic orphan glutamate delta receptors (GluD) are a type of ionotropic glutamate receptors (iGluRs) that do not bind glutamate or evoke currents when binding glycine and D-serine. They are believed to function as structural proteins that facilitate synapse formation, maturation, and maintenance in the hippocampus and cerebellum. Recent research suggests that GluD receptors have interactions with metabotropic glutamate receptors (mGlus) and are gated by their activation, with new tools and structures helping to define their role in synaptic physiology.
Article
Reproductive Biology
Alexandra Spirkova, Veronika Kovarikova, Zuzana Sefcikova, Jozef Pisko, Martina Ksinanova, Juraj Koppel, Dusan Fabian, Stefan Cikos
Summary: The study reveals that glutamic acid can affect preimplantation embryo development through cell membrane receptors. High extracellular concentrations of glutamic acid can inhibit blastocyst development, which is of practical significance.
BIOLOGY OF REPRODUCTION
(2022)
Review
Pharmacology & Pharmacy
Ananth Prasad Burada, Rajesh Vinnakota, Pratibha Bharti, Priyanka Dutta, Neelima Dubey, Janesh Kumar
Summary: GluD receptors are a subfamily of ionotropic glutamate receptors that play a crucial role in synapse formation, maturation, and maintenance of central nervous system functions. Despite the lack of knowledge about their endogenous ligands, significant discoveries have been made regarding their role in mediating trans-synaptic interactions and their unique non-swapped architecture. Additionally, the prospect of GluD ionotropic activity being regulated by direct interaction with metabotropic glutamate receptors is exciting.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Article
Environmental Sciences
Fan Yu, Lianqi Yan, Jian Sun, Yumeng Zhao, Yan Yuan, Jianhong Gu, Jianchun Bian, Hui Zou, Zongping Liu
Summary: This study found that gap junction inhibitor may play a dual role in Cd-induced cell damage by inhibiting the transmission of death signals from damaged cells to healthy cells but also aggravating the transmission of death signals between damaged cells. The Fas/FasL-mediated death receptor pathway may play an important role in this process.
ENVIRONMENTAL TOXICOLOGY
(2022)
Article
Multidisciplinary Sciences
Reuben Levy-Myers, Daniel Daudelin, Chan Hyun Na, Shanthini Sockanathan
Summary: This study demonstrates that the protein GDE3 regulates actin remodeling to release a unique subtype of extracellular vesicles (EVs) with distinct functions. GDE3 is expressed in astrocytes but not neurons and is responsible for releasing EVs containing annexin A1 and GDE3 via the protein WAVE3. Mice lacking GDE3 show decreased miniature excitatory postsynaptic current amplitudes in hippocampal neurons.
Article
Neurosciences
Chaohong Li, Baosheng Zhao, Chenlu Zhao, Lu Huang, Yuzhen Liu
Summary: The study revealed the expression and physiological function of mGluR1 in the CB. Activation of mGluR1 inhibited the response of CB to hypoxia and prolonged the latency period of the response.
FRONTIERS IN NEUROSCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Ewelina Bratek-Gerej, Apolonia Ziembowicz, Elzbieta Salinska
Summary: This study found that activation of group II mGlu receptors can prevent brain damage and regulate apoptosis and neuroprotective mechanisms in experimental birth asphyxia. Agonists LY379268 and NAAG can inhibit excessive glutamate release and apoptotic damage, and restore the concentration of neurotrophins.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Neurosciences
Prachi Ojha, Subhajit Pal, Samarjit Bhattacharyya
Summary: Norbin protein plays a critical role in the internalization process of Group I mGluRs and may be associated with mGluR-mediated synaptic plasticity.
JOURNAL OF NEUROSCIENCE
(2022)
Article
Cell Biology
Hugo Abreu, Elena Canciani, Davide Raineri, Giuseppe Cappellano, Lia Rimondini, Annalisa Chiocchetti
Summary: Tissue regeneration is a hot topic in health sciences. Studying the relationship between mesenchymal stem/stromal cells (MSCs), extracellular vesicles (EVs), and biomaterials is important for the treatment of musculoskeletal diseases.
Article
Pharmacology & Pharmacy
Monica Argenziano, Federica Bessone, Chiara Dianzani, Marie Angele Cucci, Margherita Grattarola, Stefania Pizzimenti, Roberta Cavalli
Summary: siRNA-mediated inhibition of Nrf2 can overcome chemoresistance in malignant tumors. This study designed chitosan-shelled nanobubbles for delivering siRNA against Nrf2, with a new preparation method based on a water-oil-water double-emulsion. The results showed that nanobubbles have promise as a responsive tool for siRNA delivery, able to overcome chemoresistance in melanoma cancer cells.
Article
Biochemistry & Molecular Biology
Davide Raineri, Giuseppe Cappellano, Beatrice Vilardo, Federica Maione, Nausicaa Clemente, Elena Canciani, Elena Boggio, Casimiro Luca Gigliotti, Chiara Monge, Chiara Dianzani, Renzo Boldorini, Umberto Dianzani, Annalisa Chiocchetti
Summary: This study demonstrates that the loss of ICOSL promotes tumor metastasis in breast cancer and melanoma cells, while ICOS inhibits this metastasis by promoting Treg expansion. The interaction between OPN and ICOSL is particularly important in melanoma metastasis, and interfering with this binding may be a potential therapeutic approach for nonresponding or treatment-resistant patients.
Article
Pharmacology & Pharmacy
Valentina Bordano, Gemma K. Kinsella, Stefania Cannito, Chiara Dianzani, Casimiro Luca Gigliotti, John C. Stephens, Chiara Monge, Claudia Bocca, Arianna C. Rosa, Gianluca Miglio, Umberto Dianzani, John B. C. Findlay, Elisa Benetti
Summary: This study evaluated the role of GPR21 in human macrophages, finding its involvement in cell migration and cytokine release, and the inhibition of its activity by the drug GRA2. GRA2 reduced the release of inflammatory cytokines from M1 macrophages and promoted the migration of M2 macrophages. Thus, pharmacological inhibition of GPR21 may be important in pathological conditions characterized by low-grade chronic inflammation.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Ian Stoppa, Casimiro Luca Gigliotti, Nausicaa Clemente, Deepika Pantham, Chiara Dianzani, Chiara Monge, Chiara Puricelli, Roberta Rolla, Salvatore Sutti, Filippo Reno, Renzo Boldorini, Elena Boggio, Umberto Dianzani
Summary: This study found that ICOS-Fc can improve skin wound healing by promoting angiogenesis and recruitment of reparative macrophages. This suggests that the ICOS/ICOSL network plays an important role in tissue repair.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Environmental Sciences
Gianluca Baldanzi, Beatrice Purghe, Beatrice Ragnoli, Pier Paolo Sainaghi, Roberta Rolla, Annalisa Chiocchetti, Marcello Manfredi, Mario Malerba
Summary: This study used an untargeted peptidomic approach to investigate the alterations of circulating peptides in COVID-19 patients. The results showed that peptide abundance is inversely correlated with disease severity and identified peptides related to inflammation, immune response, and coagulation processes. Additionally, changes in protein degradation patterns may be involved in the progression of the disease.
INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH
(2023)
Article
Chemistry, Multidisciplinary
Chiara Monge, Ian Stoppa, Chiara Ferraris, Annalisa Bozza, Luigi Battaglia, Luigi Cangemi, Gianluca Miglio, Stefania Pizzimenti, Nausicaa Clemente, Casimiro Luca Gigliotti, Elena Boggio, Umberto Dianzani, Chiara Dianzani
Summary: This study presents a preclinical-level test of a multi-pronged approach that inhibits melanoma growth by loading immunotherapeutic, targeted, and chemotherapeutic agents into a nanoemulsion. The approach involves the immune system and has shown promising results in subcutaneous melanoma mouse models. If translated to humans, it could achieve therapeutic efficacy without increasing the risk of toxic effects.
Article
Biochemistry & Molecular Biology
Daria Apostolo, Davide D'Onghia, Stelvio Tonello, Rosalba Minisini, Alessio Baricich, Carla Gramaglia, Filippo Patrucco, Patrizia Zeppegno, Antonio Acquaviva, Piero Emilio Balbo, Luigi Mario Castello, Giuseppe Cappellano, Annalisa Chiocchetti, Chiara Gerevini, Mara Giordano, Fatiha Laaguid, Marcello Manfredi, Davide Raineri, Cristina Rigamonti, Roberta Rolla, Valentina Romano, Marco Confalonieri, Paola Savoia, Elisa Zavattaro, Mario Pirisi, Barbara Ruaro, Pier Paolo Sainaghi, Mattia Bellan
Summary: Post-acute conditions are common after COVID-19, and the underlying mechanisms are not yet fully understood. This study suggests that Gas6 and its soluble receptors, sAxl and sMer, may be implicated in these conditions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Pharmacology & Pharmacy
Elena Boggio, Casimiro Luca Gigliotti, Ian Stoppa, Deepika Pantham, Sara Sacchetti, Roberta Rolla, Margherita Grattarola, Chiara Monge, Stefania Pizzimenti, Umberto Dianzani, Chiara Dianzani, Luigi Battaglia
Summary: The limitations of chemotherapy are side effects and drug resistance. Loading different anti-tumor drugs in nanocarriers can enhance efficacy and reduce toxicity. Nanomedicines can synergize with pharmacological, immunological, and physical combined treatments, and should be integrated in multimodal combination therapy regimens. The manuscript provides understanding and considerations for developing new nanomedicines and nanotheranostics.
Article
Pharmacology & Pharmacy
Federica Foglietta, Annalisa Bozza, Chiara Ferraris, Luigi Cangemi, Valentina Bordano, Loredana Serpe, Katia Martina, Loretta Lazzarato, Stefania Pizzimenti, Margherita Grattarola, Marie Angele Cucci, Chiara Dianzani, Luigi Battaglia
Summary: Despite advancements in cancer genomic and immunotherapies, advanced melanoma remains a life-threatening disease. In order to improve targeted drug delivery to the tumor, injectable lipid nanoemulsions were functionalized with proteins using two different approaches: chemically grafting transferrin for active targeting, and wrapping cancer cell membrane fragments for homotypic targeting. Protein functionalization was successful in both cases. Preliminary studies using flow cytometry showed that cell-membrane-fragment-wrapped nanoemulsions had higher cell uptake compared to uncoated nanoemulsions. However, transferrin grafting had a less pronounced effect in serum-enriched medium, possibly due to competition with endogenous proteins. Moreover, a more significant internalization was achieved when a pegylated heterodimer was used for conjugation (p < 0.05).
Review
Biochemistry & Molecular Biology
Barbara Azzimonti, Chiara Ballacchino, Paola Zanetta, Marie Angele Cucci, Chiara Monge, Margherita Grattarola, Chiara Dianzani, Giuseppina Barrera, Stefania Pizzimenti
Summary: Mounting evidence suggests that the microbiota plays a crucial role in the development of human diseases, including skin cancer, and is linked to oxidative stress, which is involved in the pathogenesis of various diseases. However, the connection between microbiota, oxidative stress, and skin cancer remains largely unexplored. This review discusses the current knowledge on these topics and proposes potential therapeutic strategies.
Article
Biochemistry & Molecular Biology
Marie Angele Cucci, Margherita Grattarola, Chiara Monge, Antonella Roetto, Giuseppina Barrera, Emilia Caputo, Chiara Dianzani, Stefania Pizzimenti
Summary: The use of specific inhibitors towards mutant BRAF (BRAFi) and MEK (MEKi) has improved survival rates for metastatic melanoma patients, but resistance occurs in half of the patients within the first year. This study focused on understanding the role of Nrf2 and its regulation in melanoma resistance to targeted therapies. The study found that Nrf2 was upregulated in melanoma cells resistant to therapy and that the deubiquitinase DUB3 played a role in regulating Nrf2 stability. In addition, Nrf2 was found to control the expression of YAP, and inhibiting Nrf2 or DUB3 reversed resistance to targeted therapies.
Article
Health Care Sciences & Services
Lucrezia Greta Armando, Gianluca Miglio, Raffaella Baroetto Parisi, Mariangela Esiliato, Cristina Rolando, Valeria Vinciguerra, Abdoulaye Diarassouba, Clara Cena
Summary: This observational study in the Piemonte region of Italy examined the population of newly diagnosed diabetes patients and the prescribing behavior of general practitioners. The study found that most patients received medications for cardiovascular diseases, hypertension, and infectious diseases during the treatment period. Initial antidiabetic therapy was often adjusted using SGLT-2 inhibitors and sulfonylureas.
Article
Pharmacology & Pharmacy
Francesca Della Sala, Assunta Borzacchiello, Chiara Dianzani, Elisabetta Muntoni, Monica Argenziano, Maria Teresa Capucchio, Maria Carmen Valsania, Annalisa Bozza, Sara Garelli, Maria Di Muro, Franco Scorziello, Luigi Battaglia
Summary: Solid lipid nanoparticles promote skin hydration by occluding the stratum corneum and reinforcing the skin's lipid-film barrier. The effectiveness is increased with smaller nanoparticle size and enhanced skin permeation of loaded compounds. This study optimized the Polysorbate Sorbitan Phase-Inversion Temperature method to engineer ultrasmall solid-lipid nanoparticles loaded with α-tocopherol for cosmetic application.