Gabriel Nuñez

MYPYJXKWCTUITO-UHFFFAOYSA-N vancomycin Natural products O1C (C (= C2) Cl)= CC= C2C (O) C (C (NC (C2= CC (O)= CC (O)= C2C= 2C (O)= CC= C3C= 2) C (O)= O)= O) NC (= O) C3NC (= O) C2NC (= O) C (CC (N)= O) NC (= O) C (NC (= O) C (CC (C) C) NC) C (O) C (C= C3Cl)= CC= C3OC3= CC2= CC1= C3OC1OC (CO) C (O) C (O) C1OC1CC (C)(N) C (O) C (C) O1 MYPYJXKWCTUITO-UHFFFAOYSA-N 0.000 description 11

Immune checkpoint inhibitors can stimulate antitumor immunity but can also induce toxicities termed immune-related adverse events (irAEs). Colitis is a common and severe irAE that can lead to treatment discontinuation. Mechanistic understanding of gut irAEs has been hampered because robust colitis is not observed in laboratory mice treated with checkpoint inhibitors. We report here that this limitation can be overcome by using mice harboring the microbiota of wild-caught mice, which develop overt colitis following treatment with anti-CTLA-4 antibodies. Intestinal inflammation is driven by unrestrained activation of IFNγ-producing CD4+ T cells and depletion of peripherally induced regulatory T cells through Fcγ receptor signaling. Accordingly, anti-CTLA-4 nanobodies that lack an Fc domain can promote antitumor responses without triggering colitis. This work suggests a strategy for mitigating gut irAEs while …

The ectopic gut colonization by orally derived pathobionts has been implicated in the pathogenesis of various gastrointestinal diseases, including inflammatory bowel disease (IBD). For example, gut colonization by orally derived Klebsiella spp. has been linked to IBD in mice and humans. However, the mechanisms whereby oral pathobionts colonize extra-oral niches, such as the gut mucosa, remain largely unknown. Here, we performed a high-density transposon (Tn) screening to identify genes required for the adaptation of an oral Klebsiella strain to different mucosal sites – the oral and gut mucosae – at the steady state and during inflammation. We find that K. aerogenes, an oral pathobiont associated with both oral and gut inflammation in mice, harbors a newly identified genomic locus named “locus of colonization in the inflamed gut (LIG)” that encodes genes related to iron acquisition (Sit and Chu) and host …

Neonatal skin dysbiosis to infantile atopic dermatitis: Mitigating effects of skin care Neonatal skin dysbiosis to infantile atopic dermatitis: Mitigating effects of skin care Allergy. 2024 Mar 9. doi: 10.1111/all.16095. Online ahead of print. Authors Reika Aoyama 1 , Seitaro Nakagawa 1 2 3 , Yoko Ichikawa 4 , Naohiro Inohara 3 , Yuriko Yamazaki 1 5 , Tomoka Ito 1 , Takashi Sugihira 2 , Michihiro Kono 6 , Masashi Akiyama 7 , Hiroki Takahashi 8 9 , Akiko Takaya 8 9 10 , Fumitaka Ichikawa 11 , Taiji Nakano 12 , Seiko Tanaka 13 , Yutaka Koyano 13 , Manabu Fujimoto 1 , Gabriel Núñez 3 , Naoki Shimojo 14 , Yuumi Nakamura 1 5 Affiliations 1 Department of Dermatology, Integrated Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan. 2 Department of Cutaneous Immunology and Microbiology, Graduate School of Medicine, Osaka University, Osaka, Japan. 3 Department of Pathology, University of Michigan …

BACKGROUND There is little data on the older adult ulcerative colitis (UC) population. We aimed to evaluate the prevalence of malnutrition and micronutrient deficiencies among older adults who have undergone bowel surgery for their UC. METHODS This was a single-center, retrospective study of patients 65 years and older with UC. Malnutrition was defined using the European Society for Clinical Nutrition and Metabolism (ESPEN) definition. Eight micronutrient deficiencies and nutrition-related outcomes were measured. The Saskatchewan Inflammatory Bowel Disease–Nutrition Risk Tool was utilized to identify patients at risk for malnutrition. Descriptive statistics were used to summarize data. Characteristics of patients with and without malnutrition were compared using Fisher’s exact tests (analysis of variance for age). RESULTS Eighty-eight patients with a mean age of 74.7 years were included. The most …

Bee bread (BB) is a beehive product generated upon fermentation of pollen combined with flower nectar and glandular secretions. The potential application of BB is related to its nutritional and functional components, including phenolic compounds. This is the first prospective study on palynological parameters, phenolics, antioxidant, and antibacterial activity of Chilean bee bread in vitro. The tested material exhibited high levels of phenolics (1340±186 mg GAE/100 g BB) and showed antioxidant capacity as determined by the FRAP (51±2 μmol Trolox equivalent/g BB) and ORAC‐FL (643±64 μmol Trolox equivalent/g BB) and antibacterial activity against Streptococcus pyogenes. Furthermore, the phenolic acids and flavonoids was determined using liquid chromatography‐mass spectrometry, and the concentration was determined using liquid chromatography with diode array detection. Kaempferol, quercetin …

Apoptosis is a form of regulated cell death (RCD) that involves proteases of the caspase family. Pharmacological and genetic strategies that experimentally inhibit or delay apoptosis in mammalian systems have elucidated the key contribution of this process not only to (post-)embryonic development and adult tissue homeostasis, but also to the etiology of multiple human disorders. Consistent with this notion, while defects in the molecular machinery for apoptotic cell death impair organismal development and promote oncogenesis, the unwarranted activation of apoptosis promotes cell loss and tissue damage in the context of various neurological, cardiovascular, renal, hepatic, infectious, neoplastic and inflammatory conditions. Here, the Nomenclature Committee on Cell Death (NCCD) gathered to critically summarize an abundant pre-clinical literature mechanistically linking the core apoptotic apparatus to …

The NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome is a cytoplasmic supramolecular complex that is activated in response to cellular perturbations triggered by infection and sterile injury. Assembly of the NLRP3 inflammasome leads to activation of caspase-1, which induces the maturation and release of interleukin-1β (IL-1β) and IL-18, as well as cleavage of gasdermin D (GSDMD), which promotes a lytic form of cell death. Production of IL-1β via NLRP3 can contribute to the pathogenesis of inflammatory disease, whereas aberrant IL-1β secretion through inherited NLRP3 mutations causes autoinflammatory disorders. In this review, we discuss recent developments in the structure of the NLRP3 inflammasome, and the cellular processes and signaling events controlling its assembly and activation.