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Molecular Mechanisms Underlying the Anti-Inflammatory Properties of (R)-(-)-Car...

Sousa, Cátia; Neves, Bruno Miguel; Leitão, Alcino Jorge; Mendes, Alexandrina F.

To explore the molecular mechanisms underlying the anti-inflammatory activity of (R)-(-)-carvone, we evaluated its ability to inhibit the signaling pathways involving the mitogen-activated protein kinases (MAPKs) and the transcription factor, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). (R)-(-)-carvone significantly decreased c-Jun N-terminal kinase (JNK) 1phosphorylation, but not tha...


Development of an in chemico high-throughput screening method for the identific...

Ferreira, Isabel; Brites, Gonçalo; Silva, Ana; Caramelo, Francisco; Oliveiros, Bárbara; Neves, Bruno Miguel; Cruz, Maria Teresa

It is well established that chemical-peptide conjugation represents the molecular initiating event (MIE) in skin sensitization. This MIE has been successfully exploited in the development of in chemico peptide reactivity assays, with the Direct Peptide Reactivity Assay (DPRA) being validated as a screening tool for skin sensitization hazard as well as an OECD test guideline. This test relies on the use of a hig...


Elucidation of the Mechanism Underlying the Anti-Inflammatory Properties of (S)...

Sousa, Cátia; Neves, Bruno Miguel; Leitão, Alcino Jorge; Mendes, Alexandrina Ferreira

The signaling pathways involved in age-related inflammation are increasingly recognized as targets for the development of preventive and therapeutic strategies. Our previous study elucidated the structure-activity relationship of monoterpene compounds derived from p-menthane as potential anti-inflammatory drugs and identified (S)-(+)-carvone as the most potent among the compounds tested. This study aims at iden...


Pharmacological combination of nivolumab with dendritic cell vaccines in cancer...

Calmeiro, João; Carrascal, Mylène A.; Tavares, Adriana Ramos; Ferreira, Daniel Alexandre; Gomes, Célia; Cruz, Maria Teresa; Falcão, Amílcar

In the last decade, immunotherapy led to a paradigm shift in the treatment of numerous malignancies. Alongside with monoclonal antibodies blocking programmed cell death receptor-1 (PD-1)/PD-L1 and cytotoxic T- lymphocyte antigen 4 (CTLA-4) immune checkpoints, cell-based approaches such as CAR-T cells and dendritic cell (DC) vaccines have strongly contributed to pushing forward this thrilling field. While initia...


In-Depth Analysis of the Impact of Different Serum-Free Media on the Production...

Calmeiro, João; Mendes, Luís; Duarte, Iola F.; Leitão, Catarina; Tavares, Adriana R.; Ferreira, Daniel Alexandre; Gomes, Célia; Serra, João

Dendritic cell (DC)-based antitumor vaccines have proven to be a safe approach, but often fail to generate robust results between trials. Translation to the clinic has been hindered in part by the lack of standard operation procedures for vaccines production, namely the definition of optimal culture conditions during ex-vivo DC differentiation. Here we sought to compare the ability of three clinical grade serum...


Strategies for Cancer Immunotherapy Using Induced Pluripotency Stem Cells-Based...

Bernardes de Jesus, Bruno; Neves, Bruno Miguel; Ferreira, Manuela; Nóbrega-Pereira, Sandrina

Despite improvements in cancer therapy, metastatic solid tumors remain largely incurable. Immunotherapy has emerged as a pioneering and promising approach for cancer therapy and management, and in particular intended for advanced tumors unresponsive to current therapeutics. In cancer immunotherapy, components of the immune system are exploited to eliminate cancer cells and treat patients. The recent clinical su...


Dendritic Cell Vaccines for Cancer Immunotherapy: The Role of Human Conventiona...

Calmeiro, João; Carrascal, Mylène A.; Tavares, Adriana Ramos; Ferreira, Daniel Alexandre; Gomes, Célia; Falcão, Amílcar; Cruz, Maria Teresa

Throughout the last decades, dendritic cell (DC)-based anti-tumor vaccines have proven to be a safe therapeutic approach, although with inconsistent clinical results. The functional limitations of ex vivo monocyte-derived dendritic cells (MoDCs) commonly used in these therapies are one of the pointed explanations for their lack of robustness. Therefore, a great effort has been made to identify DC subsets with s...


NLRP3 Inflammasome and Allergic Contact Dermatitis: A Connection to Demystify

Sebastião, Ana Isabel; Ferreira, Isabel; Brites, Gonçalo; Silva, Ana; Neves, Bruno Miguel; Cruz, Maria Teresa

Allergic contact dermatitis is a common occupational disease that manifests as a cell-mediated hypersensitivity reaction following skin exposure to small reactive chemicals termed haptens. Haptens penetrate the stratum corneum and covalently modify proteins in the epidermis, inducing intracellular stress, which further leads to the release of damage-associated molecular patterns (DAMPs), such as uric acid, reac...


Standardised comparison of limonene-derived monoterpenes identifies structural ...

Sousa, Cátia; Leitão, Alcino Jorge; Neves, Bruno Miguel; Judas, Fernando; Cavaleiro, Carlos; Mendes, Alexandrina F.

Mint species are widely used in traditional and conventional medicine as topical analgesics for osteoarthritic pain and for disorders of the gastrointestinal and respiratory tracts which are all associated with chronic inflammation. To identify the structural determinants of anti-inflammatory activity and potency which are required for chemical optimization towards development of new anti-inflammatory drugs, a ...


Giardia lamblia Decreases NF-κB p65RelA Protein Levels and Modulates LPS-Induce...

Faria, Clarissa Perez; Neves, Bruno Miguel; Lourenço, Ágata; Cruz, Maria Teresa; Martins, João D.; Silva, Ana; Pereira, Sónia; Sousa, Maria do Céu

The protozoan Giardia lamblia is the most common cause of parasitic gastrointestinal infection worldwide. The parasite developed sophisticated, yet not completely disclosed, mechanisms to escape immune system and growth in the intestine. To further understand the interaction of G. lamblia with host immune cells, we investigated the ability of parasites to modulate the canonical activation of mouse macrophages (...


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