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Inorganic Chemical Pollutants
Published in William J. Rea, Kalpana D. Patel, Reversibility of Chronic Disease and Hypersensitivity, Volume 4, 2017
William J. Rea, Kalpana D. Patel
In the striatum, however, mRNA levels for all three factors were elevated in both exposure groups. Interestingly, although the TH loss persisted, these inflammatory indicators were resolved by 105 days postexposure, mRNA levels for NOS2 were elevated in both exposure groups in both the striatum and the midbrain, but NOS1, NOS3, COX-2, and HO-1 mRNA levels remained unchanged. A microglial response, as determined by increased mRNA levels for Emr1 (f/80) and Itgam (OX42) in the midbrain, accompanied the TH loss in the striatum and midbrain of the high-Mn exposure group only.
A review of antibody-based therapeutics targeting G protein-coupled receptors: an update
Published in Expert Opinion on Biological Therapy, 2020
Building on the success of antibody-based therapies, alternative scaffolds (such as nanobodies and i-bodies) are also making headway in targeting GPCRs, such as the CXCR4-targeting i-body discovered by AdAlta will shortly enter a first-in-human Phase 1 trial [71]. In addition to bispecific antibodies and ADCs in early clinical development, there are now at least two CAR-T therapies in the research pipeline at the preclinical stage. These target EMR1, an aGPCR, for the treatment of eosinophilic leukemia [72] and GPRC5D, an orphan GPCR, for the treatment of multiple myeloma [73]. Another important area of interest in the field of antibody engineering is the use of BBB receptor-mediated transcytosis delivery (e.g., via the transferrin receptor) which could equally be applied to GPCR targeting using antibody-based modalities. Such a hybrid approach could open up the field of targeting opportunities further for the delivery of antibodies and small-molecule drugs. A number of organizations are pursuing this approach, such as Denali Therapeutics who have developed a transport vehicle (TV) platform for the delivery of enzymes, antibodies, proteins, and oligonucleotides. Lastly, the potential of antibody-peptide fusions is another hybrid approach that is being evaluated but is still mainly in an early research stage other than the example of glutazumab mentioned previously.
Periodontitis: a newly identified comorbidity in psoriasis and psoriatic arthritis
Published in Expert Review of Clinical Immunology, 2020
Szandra Dalmády, Lajos Kemény, Márk Antal, Rolland Gyulai
The genetic risk loci for CP have been investigated in candidate-gene studies. These studies focused on genes related to host immunity and inflammatory response and examined polymorphisms in the IL-1, IL-6, Fc gamma receptor 2A, TNF-α, human vitamin D receptor, cluster of differentiation (CD)-14, MMP-1, toll-like receptors (TLRs), cyclooxygenase-2 and C-reactive protein genes. Most studies, however, yielded mixed results. IL-1 gene variations have been most consistently associated (significant associations reported for 19 of 27 studies) with severe or progressive CP in Caucasians, and these results were validated in two meta-analyses [50,51]. GWASs of CP have also been performed, and, although these efforts have identified several susceptibility genes, including C5AR1, DLG2, FAM180A, MFSD1, NCR2, NPY, EMR1, VAV1, GLT6D1 WHAMM and AP3B2, these studies – defined by clinical criteria alone – have had modest success [52–56].
Hypereosinophilic syndromes in the precision medicine era: clinical, molecular aspects and therapeutic approaches (targeted therapies)
Published in Expert Review of Hematology, 2019
Alessandra Iurlo, Daniele Cattaneo, Umberto Gianelli
Finally, promising antibodies deserve further clinical investigations. Sialic acid-binding immunoglobulin-like lectin (Siglec) 8 highly expressed in eosinophils represents a possible new target; chimeric antibodies directed to Siglec 8, in vitro in the presence of IL-5 and in vivo in mice with IL-5-induced eosinophilia, achieved a marked eosinophils killing [110]. The epidermal growth factor-like module containing mucin-like hormone receptor 1 (EMR1), a receptor restricted to mature eosinophils, might also represent a drugable target in HES. An afucosylated anti-EMR1 antibody turned out to be extremely active both in vitro and in vivo in monkeys inducing a marked eosinophils suppression [111]. Molecular genetics together with targeted agents will pave the way of future research on HES.