Search

The cyclic peptide cyclo(Val-Leu-Leu-D-Phe-Pro)2 (peptide 1) was specifically designed for structural chemistry investigations, drawing inspiration from Gramicidin S (GS). Previous studies have shown that Pro residues within 1 adopt a down-puckering conformation of the pyrrolidine ring. By incorporating fluoride-Pro with 4-trans/cis-isomers into 1, an up-puckering conformation was successfully induced. In the current investigation, introducing hydroxyprolines with 4-trans/cis-isomer configurations (tHyp/cHyp) into 1 gave cyclo(Val-Leu-Leu-D-Phe-tHyp)2 methanol disolvate monohydrate, C62H94N10O12·2CH4O·H2O (4), and cyclo(Val-Leu-Leu-D-Phe-cHyp)2 monohydrate, C62H94N10O12·H2O (5), respectively. However, the puckering of 4 and 5 remained in the down conformation, regardless of the geometric position of the hydroxyl group. Although the backbone structure of 4 with trans-substitution was asymmetric, the asymmetric backbone of 5 with cis-substitution was unexpected. It is speculated that the anticipated influence of stress from the geometric positioning, which was expected to affect the puckering, may have been mitigated by interactions between the hydroxyl groups of hydroxyproline, the solvent molecules, and peptides. [ABSTRACT FROM AUTHOR]

Introduction: Contact hypersensitivity (CHS), a type of delayed‐type hypersensitivity, is induced by hapten exposure to the skin and mucosa. We previously reported that, in a murine model of CHS, the vaginal mucosa (VM) sensitization showed lower T‐cell responses as compared with the abdominal skin sensitization. To investigate mechanisms of impaired CHS by the VM sensitization, we compared migration of hapten‐captured dendritic cells (DCs) in the draining lymph nodes (dLNs) and recruitment of DCs at the sensitized local sites. Methods: Fluorescein isothiocyanate (FITC) or 2,4‑dinitrofluorobenzene (DNFB) was used as hapten, and migration of FITC+ DCs in the dLNs and local recruitment of MHC class II+ and CD11c+ cells were compared between abdominal skin and VM sensitization by flow cytometric analyses and immunohistochemistry. Expression of tumor growth factor (TGF)‐β at mRNA and protein levels, and local recruitment of CD206+ cells were examined after VM sensitization. Results: VM sensitization showed less numbers of FITC+MHC class IIhighCD11c+ migratory DCs in the dLNs at 6 and 24 h, as compared with skin sensitization. Both skin and VM sensitization induced the recruitment of dermal/submucosal DCs at 6 h, but the number of submucosal DCs in the VM was significantly decreased at 24 h. VM showed persistently higher mRNA levels of TGF‐β2/β3 expression than those of the skin before and after sensitization. In the VM sensitization, increment of CD206+MHC class II+ cells was observed especially at the deep lamina propria at 24 h. Most of CD206+ cells were also positive for the binding to Fc chimeric TGF‐β receptor that interacts with all TGF‐β isoforms, suggesting TGF‐β expression. Conclusion: DC migration to dLNs and localization of DCs at the sensitized sites are limited in the VM sensitization. Our results suggest that the existence of TGF‐β‐expressing CD206+ cells may contribute less sensitization ability and CHS responses in the VM. [ABSTRACT FROM AUTHOR]

Pheromones are crucial for eliciting social and sexual behaviors in diverse animal species. The vomeronasal receptor type-1 (V1R) genes, encoding members of a pheromone receptor family, are highly variable in number and repertoire among mammals due to extensive gene gain and loss. Here, we report a novel pheromone receptor gene belonging to the V1R family, named ancient V1R (ancV1R), which is shared among most Osteichthyes (bony vertebrates) from the basal lineage of ray-finned fishes to mammals. Phylogenetic and syntenic analyses of ancV1R using 115 vertebrate genomes revealed that it represents an orthologous gene conserved for >400 My of vertebrate evolution. Interestingly, the loss of ancV1R in some tetrapods is coincident with the degeneration of the vomeronasal organ in higher primates, cetaceans, and some reptiles including birds and crocodilians. In addition, ancV1R is expressed in most mature vomeronasal sensory neurons in contrast with canonical V1R s, which are sparsely expressed in a manner that is consistent with the "one neuron–one receptor" rule. Our results imply that a previously undescribed V1R gene inherited from an ancient Silurian ancestor may have played an important functional role in the evolution of vertebrate vomeronasal organ. [ABSTRACT FROM AUTHOR]

The cyclic peptide cyclo (Val-Leu-Leu-d-Phe-Pro) 2 (peptide 1 ) was specifically designed for structural chemistry investigations, drawing inspiration from Gramicidin S (GS). Previous studies have shown that Pro residues within 1 adopt a down-puckering conformation of the pyrrolidine ring. By incorporating fluoride-Pro with 4- trans / cis -isomers into 1 , an up-puckering conformation was successfully induced. In the current investigation, introducing hy-droxy-prolines with 4- trans / cis -isomer configurations (tHyp/cHyp) into 1 gave cyclo (Val-Leu-Leu-d-Phe-tHyp) 2 methanol disolvate monohydrate, C 62 H 94 N 10 O 12 ·2CH 4 O·H 2 O ( 4 ), and cyclo (Val-Leu-Leu-d-Phe-cHyp) 2 monohydrate, C 62 H 94 N 10 O 12 ·H 2 O ( 5 ), respectively. However, the puckering of 4 and 5 remained in the down conformation, regardless of the geometric position of the hydroxyl group. Although the backbone structure of 4 with trans -substitution was asymmetric, the asymmetric backbone of 5 with cis -substitution was unexpected. It is speculated that the anti-cipated influence of stress from the geometric positioning, which was expected to affect the puckering, may have been mitigated by inter-actions between the hydroxyl groups of hy-droxy-proline, the solvent mol-ecules, and peptides., (© Asano et al. 2024.)

Some patients with developmental and epileptic encephalopathy (DEE) respond to adrenocorticotropic hormone (ACTH) therapy but relapse soon after. While long-term ACTH therapy (LT-ACTH) has been attempted for these patients, no previous studies have carefully assessed adrenal function during LT-ACTH. We evaluated the effectiveness of LT-ACTH, as well as adverse effects (AE), including their adrenal function in three DEE patients. Patients underwent a corticotropin-releasing hormone (CRH) stimulation test during LT-ACTH, and those with peak serum cortisol below 15 μg/dL were considered to be at high risk of adrenal insufficiency (AI). Two of three responded, and their life-threatening seizures with postgeneralized electroencephalogram (EEG) suppression decreased. Although no individuals had serious AE, CRH stimulation test revealed relatively weak responses, without reaching normal cortisol peak level (18 μg/dL). Hydrocortisone replacement during stress was prepared in a case with lower cortisol peak than our cutoff level. LT-ACTH could be a promising treatment option for cases of DEE that relapse soon after effective ACTH treatment. The longer duration and larger cumulative dosage in LT-ACTH than in conventional ACTH could increase the relative risk of AI. Careful evaluation with pediatric endocrinologists, including hormonal stimulation tests, might be useful for continuing this treatment safely., (© 2021 The Authors. Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)