2023 FDA TIDES (Peptides and Oligonucleotides) Harvest

A total of nine TIDES (pepTIDES and oligonucleoTIDES) were approved by the FDA during 2023. The approved four oligonucleotide are indicated for various types of disorders, including amyotrophic lateral sclerosis, geographic atrophy, primary hyperoxaluria type 1, and polyneuropathy of hereditary transthyretin-mediated amyloidosis. All oligonucleotides showed chemically modified structures, to enhance their stability and therapeutic effectiveness as antisense or aptamer oligomers. Some of them demonstrate various types of conjugation to driving ligands. The approved peptides comprise various structures including linear, cyclic, lipopeptides and with diverse applications. Interestingly, the FDA has granted an orphan drug designation for a first peptide-based drug as a highly selective chemokine antagonist. Furthermore, Rett syndrome has found its first ever core symptoms treatment, which is also peptide-based one. Here we analyse the TIDES approved in 2023 on the basis of their chemical structure, medical target, mode of action, administration route, and common adverse effects

2022 FDA TIDES (peptides and oligonucleotides) harvest

A total of 37 new drug entities were approved in 2022; although that year registered the lowest number of drug approvals since 2016, the TIDES class consolidated its presence with a total of five authorizations (four peptides and one oligonucleotide). Interestingly, 23 out of 37 drugs were first-in-class and thus received fast-track designation by the FDA in categories such as breakthrough therapy, priority review voucher, orphan drug, accelerated approval, and so on. Here, we analyze the TIDES approved in 2022 on the basis of their chemical structure, medical target, mode of action, administration route, and common adverse effects

2021 FDA TIDES (peptides and oligonucleotides) harvest

From the medical, pharmaceutical, and social perspectives, 2021 has been a year dominated by the COVID-19 pandemic. However, despite this global health crisis, the pharmaceutical industry has continued its endeavors, and 2021 could be considered an excellent year in terms of the drugs accepted by the US Food and Drug Administration (FDA). Thus, during this year, the FDA has approved 50 novel drugs, of which 36 are new chemical entities and 14 biologics. It has also authorized 10 TIDES (8 peptides, 2 oligonucleotides), in addition to 2 antibody-drug conjugates (ADCs) whose structures contain peptides. Thus, TIDES have accounted for about 24% of the approvals in the various drug categories. Importantly, this percentage has surpassed the figure in 2020 (10%), thus reflecting the remarkable success of TIDES. In this review, the approved TIDE-based drugs are analyzed on the basis of their chemical structure, medical target, mode of action, administration route, and adverse effects

Metabolic and functional impairment of CD8+ T cells from the lungs of influenza-infected obese mice

Obesity is an independent risk factor for morbidity and mortality in response to influenza infection. However, the underlying mechanisms by which obesity impairs immunity are unclear. Herein, we investigated the effects of diet-induced obesity on pulmonary CD8+ T cell metabolism, cytokine production, and transcriptome as a potential mechanism of impairment during influenza virus infection in mice. Male C57BL/6J lean and obese mice were infected with sub-lethal mouse-adapted A/PR/8/34 influenza virus, generating a pulmonary anti-viral and inflammatory response. Extracellular metabolic flux analyses revealed pulmonary CD8+ T cells from obese mice, compared with lean controls, had suppressed oxidative and glycolytic metabolism at day 10 post-infection. Flow cytometry showed the impairment in pulmonary CD8+ T cell metabolism with obesity was independent of changes in glucose or fatty acid uptake, but concomitant with decreased CD8+ GrB+ IFNγ+ populations. Notably, the percent of pulmonary effector CD8+ GrB+ IFNγ+ T cells at day 10 post-infection correlated positively with total CD8+ basal extracellular acidification rate and basal oxygen consumption rate. Finally, next-generation RNA sequencing revealed complex and unique transcriptional regulation of sorted effector pulmonary CD8+ CD44+ T cells from obese mice compared to lean mice following influenza infection. Collectively, the data suggest diet-induced obesity increases influenza virus pathogenesis, in part, through CD8+ T cell-mediated metabolic reprogramming and impaired effector CD8+ T cell function

Inflammation and Metabolism of Influenza-Stimulated Peripheral Blood Mononuclear Cells From Adults With Obesity Following Bariatric Surgery

BACKGROUND: Obesity dysregulates immunity to influenza infection. Therefore, there is a critical need to investigate how obesity impairs immunity and to establish therapeutic approaches that mitigate the impact of increased adiposity. One mechanism by which obesity may alter immune responses is through changes in cellular metabolism. METHODS: We studied inflammation and cellular metabolism of peripheral blood mononuclear cells (PBMCs) isolated from individuals with obesity relative to lean controls. We also investigated if impairments to PBMC metabolism were reversible upon short-term weight loss following bariatric surgery. RESULTS: Obesity was associated with systemic inflammation and poor inflammation resolution. Unstimulated PBMCs from participants with obesity had lower oxidative metabolism and adenosine triphosphate (ATP) production compared to PBMCs from lean controls. PBMC secretome analyses showed that ex vivo stimulation with A/Cal/7/2009 H1N1 influenza led to a notable increase in IL-6 with obesity. Short-term weight loss via bariatric surgery improved biomarkers of systemic metabolism but did not improve markers of inflammation resolution, PBMC metabolism, or the PBMC secretome. CONCLUSIONS: These results show that obesity drives a signature of impaired PBMC metabolism, which may be due to persistent inflammation. PBMC metabolism was not reversed after short-term weight loss despite improvements in measures of systemic metabolism

Human-Computer Interaction and the Future ofWork

Advances in computing technology, changing policies, and slow crises are rapidly changing the way we work. Human-computer interaction (HCI) is a critical aspect of these trends, to understand how workers contend with emerging technologies and how design might support workers and their values and aspirations amidst technological change. This SIG invites HCI researchers across diverse domains to reflect on the range of approaches to future of work research, recognize connections and gaps, and consider how HCI can support workers and their wellbeing in the future

Determinants of Carbon Emission Disclosures and UN Sustainable Development Goals: The Case of UK Higher Education Institutions

In recent years, organisational sustainability has become a topical issue in many institutional fields and a number of calls have been made to improve the disclosure of carbon information as part of sustainability efforts. This paper responds to these calls, chiefly examining the determinants of (CED) in the annual reports of UK higher education institutions (HEIs). It also aims to predict the relationship between the extent of CED and UN Sustainable Development Goals (SDGs) reporting by UK universities. We construct a disclosure index to capture the extent and type of CED in the annual reports of UK HEIs, finding that carbon reduction targets imposed by the Government, environmental audit, and the amount of actual carbon emissions are significant and positively associated with CED. However, we find no relationship between CED and the disclosure of SDGs. We argue that HEIs'. CED can be useful in developing relevant regulatory policies given the targets are carefully set. Our research has important implications for policymakers regarding carbon reduction targets and related non?mandatory guidance, as these can be utilised as an effective mechanism in increasing carbon emission disclosure voluntary CED that are integrated into SDG disclosures