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Abstract Gut microbiota affect transplantation outcomes; however, the influence of immunosuppression and cell therapy on the gut microbiota in cardiovascular care remains unexplored. We investigated gut microbiota dynamics in a nonhuman primate (NHP) cardiac ischemia/reperfusion model while under immunosuppression and receiving cell therapy with human induced pluripotent stem cell (hiPSC)-derived endothelial cells (EC) and cardiomyocytes (CM). Both immunosuppression and EC/CM co-treatment increased gut microbiota alpha diversity. Immunosuppression promoted anaerobes, such as Faecalibacterium, Streptococcus, Anaerovibrio and Dialister, and altered amino acid metabolism and nucleosides/nucleotides biosynthesis in host plasma. EC + CM cotreatment favors Phascolarctobacterium, Fusicatenibacter, Erysipelotrichaceae UCG-006, Veillonella and Mailhella. Remarkably, gut microbiota of the EC/CM co-treatment group resembled that of the pre-injury group, and the NHPs exhibited a metabolic shift towards amino acid and fatty acid/lipid biosynthesis in plasma following cell therapy. The interplay between shift in microbial community and host homeostasis during treatment suggests gut microbiome modulation could improve cell therapy outcomes.

Abstract We conducted a phase I trial to determine the optimal dose of triplet therapy with the tyrosine kinase inhibitor sitravatinib plus nivolumab plus ipilimumab in 22 previously untreated patients with advanced clear cell renal cell carcinoma. The primary endpoint was safety. Secondary endpoints were objective response rate (ORR), disease control rate (DCR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), 1-year survival probability, and sitravatinib pharmacokinetics. Sitravatinib dose of 35 mg daily plus nivolumab 3 mg/kg and ipilimumab 1 mg/kg resulted in high frequency of immune-related adverse events. Subsequent dose reduction of ipilimumab to 0.7 mg/kg allowed safe escalation of sitravatinib up to 100 mg daily. Overall, the triplet combination achieved ORR 45.5%, DCR 86.4%, median PFS 14.5 months, and 1-year survival 80.8%. Median OS and DOR were not reached. Sitravatinib exposure increased dose-dependently. Single-cell RNA-seq of longitudinally collected tumor biopsies from 12 patients identified a tumor cell-specific epithelial-mesenchymal transition-like program associated with treatment resistance and poor outcomes. Treatment resistance was characterized by a transition from cytotoxic to exhausted T cell state and enrichment for M2-like myeloid cells. The observed hypothesis-generating changes in gene expression dynamics and cellular states may help inform future strategies to optimize immunotherapy efficacy. Clinical Trials.gov identifier: NCT04518046

Abstract Background The objective of this systematic review was to review the current evidence on the effects of acute exercise with and without morning breakfast consumption on cognitive performance. Methods This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines and is registered in the International Prospective Register of Systematic Reviews (CRD42023396125). Studies were included if they investigated effects of acute exercise with and without preceding morning breakfast on cognitive performance measured during and following exercise in healthy adults. Eligible studies from 5 electronic databases, PubMed, Scopus, MEDLINE, Web of Science, and Embase, with no limitations on years and dates of publications to retrieve maximal number of literature (literature search and screen were completed on 13 December 2024). Study quality was assessed using the Physiotherapy Evidence Database scale (PEDro). Results A total of 3018 studies were screened. Five studies, involving 70 participants (42 women, aged between 18 and 50 years) in total (sample size per study: 10–24), were eligible for inclusion in this review. The synthesised results based on 5 identified studies with healthy adults showed that there was no indication that effects of exercise on cognitive performance (e.g., processing speed, inhibitory control) are altered by breakfast skipping and/or consumption (e.g., different portion, macronutrients, and contents). The included studies had a mean PEDro score of 4.0 (scored between 3 and 5), suggesting ‘fair’ methodological quality. Conclusion The synthesised results showed that there was no indication that effects of exercise on cognitive performance (e.g., processing speed, inhibitory control) are altered by morning breakfast consumption or macronutrients and contents of breakfast in healthy adults. However, the synthesised results should be interpreted cautiously, given the limited evidence and the heterogeneity in methodology with mostly involved young and healthy adults. Further investigation regarding interactive effects of breakfast and exercise on cognition, especially in individuals with metabolic disease or medical conditions, is warranted.