What Doesn't Kill You Makes You Stronger? Examining Relationships Between Early‐Life Stress, Later‐Life Inflammation and Mortality Risk in Skeletal Remains DOI Creative Commons
Ben Wigley, Eleanor Stillman, Elizabeth Craig‐Atkins

et al.

American Journal of Physical Anthropology, Journal Year: 2025, Volume and Issue: 186(2)

Published: Feb. 1, 2025

ABSTRACT Objectives This paper explores conflicting perspectives on the adaptive significance of phenotypic plasticity during fetal and early postnatal development impact that stressors experienced this critical early‐life period have later‐life morbidity mortality risk. Methods The sample ( n = 216) comprised archeologically‐recovered human skeletons. A geometric morphometric (GM) method was employed to evaluate first permanent molar (M1) fluctuating asymmetry (FA) provide a proxy for stress. Shifts in physiology were inferred through two inflammatory lesions: periosteal new bone formation (PNBF) periodontal disease (PD). To explore risk, age‐at‐death estimated dental skeletally immature individuals 104) senescent skeletal changes mature skeletons 112). Results Significant differences found M1 FA between groups, with cohort associated elevated FA. Within‐group analysis revealed group had significant positive relationship PD presence. In group, alongside sex co‐occurrence PNBF, predictor shorter life. Higher also active bilaterally expressed PNBF. Conclusions It is theorized stress, if survived, programmed hyperinflammatory response environmentally‐mediated physiological perturbations which increased chances survival subsequent but Findings demonstrate complicated developmental stress shifts helps illustrate programming support Thrifty Phenotype hypothesis.

Language: Английский

Efficacy and safety of baricitinib plus standard of care for the treatment of critically ill hospitalised adults with COVID-19 on invasive mechanical ventilation or extracorporeal membrane oxygenation: an exploratory, randomised, placebo-controlled trial DOI
E. Wesley Ely, Athimalaipet V Ramanan, Cynthia E. Kartman

et al.

The Lancet Respiratory Medicine, Journal Year: 2022, Volume and Issue: 10(4), P. 327 - 336

Published: Feb. 3, 2022

Language: Английский

Citations

171
Prospective Roles of Tumor Necrosis Factor-Alpha (TNF-α) in COVID-19: Prognosis, Therapeutic and Management DOI Open Access
Zarina Mohd Zawawi,

Jeevanathan Kalyanasundram,

Rozainanee Mohd Zain

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(7), P. 6142 - 6142

Published: March 24, 2023

The coronavirus disease 2019 (COVID-19) became a worldwide concern at the beginning of 2020 and has affected millions. Several previous studies revealed impact imbalanced innate immune response on progression COVID-19 its outcomes. High levels proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-α) interleukins are produced readily by cells to fight Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) infections. Nonetheless, cytokine-mediated inflammatory events also linked detrimental lung injury respiratory failure, which can result in deaths among patients. TNF-α is amongst early mediate responses enhance cell infiltration SARS-CoV-2 In COVID-19, TNF-α-mediated inflammation cause tissue damage gradually promotes fibrosis, later results pneumonia, pulmonary edema, acute distress syndrome. This review, therefore, aims deliberate immunomodulatory roles promoting relation with morbidity mortality. addition, this review proposes potential biomarker for prognosis severe related complications molecular target anti-TNF-α therapy.

Language: Английский

Citations

45
Signaling pathways and potential therapeutic targets in acute respiratory distress syndrome (ARDS) DOI Creative Commons
Qianrui Huang, Yue Le, Shusheng Li

et al.

Respiratory Research, Journal Year: 2024, Volume and Issue: 25(1)

Published: Jan. 13, 2024

Abstract Acute respiratory distress syndrome (ARDS) is a common condition associated with critically ill patients, characterized by bilateral chest radiographical opacities refractory hypoxemia due to noncardiogenic pulmonary edema. Despite significant advances, the mortality of ARDS remains unacceptably high, and there are still no effective targeted pharmacotherapeutic agents. With outbreak coronavirus disease 19 worldwide, has increased correspondingly. Comprehending pathophysiology underlying molecular mechanisms may thus be essential developing therapeutic strategies reducing mortality. To facilitate further understanding its pathogenesis exploring novel therapeutics, this review provides comprehensive information from presents therapeutics. We first describe that involve dysregulated inflammation, alveolar-capillary barrier dysfunction, impaired alveolar fluid clearance oxidative stress. Next, we summarize signaling pathways related above four aspects pathophysiology, along latest research progress. Finally, discuss emerging show exciting promise in ARDS, including several pharmacologic therapies, microRNA-based therapies mesenchymal stromal cell highlighting pathophysiological basis influences on signal transduction for their use.

Language: Английский

Citations

22
An interferon-stimulated long non-coding RNA USP30-AS1 as an immune modulator in influenza A virus infection DOI Creative Commons
Yi Cao, Alex W. H. Chin, Haogao Gu

et al.

PLoS Pathogens, Journal Year: 2025, Volume and Issue: 21(1), P. e1012854 - e1012854

Published: Jan. 8, 2025

Long non-coding RNAs (lncRNAs) are essential components of innate immunity, maintaining the functionality immune systems that control virus infection. However, how lncRNAs engage responses during influenza A (IAV) infection remains unclear. Here, we show lncRNA USP30-AS1 is up-regulated by multiple different IAV subtypes and required for tuning inflammatory antiviral response in Genetically inactivation enhances viral protein synthesis growth. an interferon-stimulated gene, induction can be achieved JAK-STAT mediated signaling activation. The regulation independent its proximal protein-coding gene USP30 . In infection, deletion unleashes high systemic involving a broad range pro-inflammatory factors, suggesting as critical modulator Furthermore, established database providing well-annotated host expression profiles or stimulation.

Language: Английский

Citations

2
Long-Term Cardiovascular Effects of COVID-19: Emerging Data Relevant to the Cardiovascular Clinician DOI Open Access

Diana L. Tobler,

Alix J. Pruzansky,

Sahar Naderi

et al.

Current Atherosclerosis Reports, Journal Year: 2022, Volume and Issue: 24(7), P. 563 - 570

Published: May 4, 2022

Language: Английский

Citations

68
Pyroptosis in host defence against bacterial infection DOI Creative Commons
Dominik Brokatzky, Serge Mostowy

Disease Models & Mechanisms, Journal Year: 2022, Volume and Issue: 15(7)

Published: July 1, 2022

ABSTRACT Pyroptosis, a regulated form of pro-inflammatory cell death, is characterised by lysis and the release cytokines, damage- pathogen-associated molecular patterns. It plays an important role during bacterial infection, where it can promote inflammatory response eliminate replicative niche intracellular pathogens. Recent work, using variety pathogens, has illuminated versatility pyroptosis, revealing unexpected concepts underlying host defence. In this Review, we overview mechanisms pyroptosis discuss their in defence, from single to whole organism. We focus on recent studies three cellular microbiology paradigms – Mycobacterium tuberculosis, Salmonella Typhimurium Shigella flexneri that have transformed field pyroptosis. compare insights discovered tissue culture, zebrafish mouse models, highlighting advantages disadvantages these complementary infection models investigate for modelling human infection. Moving forward, propose in-depth knowledge obtained better inform future higher vertebrates, including humans, help develop innovative host-directed therapies combat

Language: Английский

Citations

40
Genetic susceptibility to severe COVID-19 DOI Creative Commons
Claudio Cappadona, Valeria Rimoldi, Elvezia Maria Paraboschi

et al.

Infection Genetics and Evolution, Journal Year: 2023, Volume and Issue: 110, P. 105426 - 105426

Published: March 17, 2023

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiologic agent of disease 2019 (COVID-19) pandemic. Clinical manifestations range from an asymptomatic condition to life-threatening events and death, with more severe courses being associated age, male sex, comorbidities. Besides these risk factors, intrinsic characteristics virus as well genetic factors host are expected account for COVID-19 clinical heterogeneity. Genetic studies have long been recognized fundamental identify biological mechanisms underlying congenital diseases, pinpoint genes/proteins responsible susceptibility different inherited conditions, highlight targets therapeutic relevance, suggest drug repurposing, even clarify causal relationships that make modifiable some environmental factors. Though usually take time be concluded and, above all, translate their discoveries patients' bedside, scientific community moved really fast deliver signals phenotypes. In this Review, besides a concise description symptomatology SARS-CoV-2 mechanism infection, we aimed recapitulate current literature in terms specifically associate increased severity disease.

Language: Английский

Citations

26
Incidence of new-onset hypertension before, during, and after the COVID-19 pandemic: a 7-year longitudinal cohort study in a large population DOI Creative Commons
Valentina Trimarco, Raffaele Izzo, Daniela Pacella

et al.

BMC Medicine, Journal Year: 2024, Volume and Issue: 22(1)

Published: March 19, 2024

Abstract Background While the augmented incidence of diabetes after COVID-19 has been widely confirmed, controversial results are available on risk developing hypertension during pandemic. Methods We designed a longitudinal cohort study to analyze closed followed up over 7-year period, i.e., 3 years before and pandemic, 2023, when pandemic was declared be over. analyzed medical records more than 200,000 adults obtained from cooperative primary physicians January 1, 2017, December 31, 2023. The main outcome new diagnosis hypertension. Results evaluated 202,163 individuals in pre-pandemic 190,743 years, totaling 206,857 including 2023 data. rate 2.11 (95% C.I. 2.08–2.15) per 100 person-years 2017–2019, increasing 5.20 5.14–5.26) period 2020–2022 (RR = 2.46), 6.76 6.64–6.88) marked difference trends between first two successive observation periods substantiated by fitted regression lines Poisson models conducted monthly log-incidence Conclusions detected significant increase new-onset which at end affected ~ 20% studied cohort, percentage higher infection within same time frame. This suggests that increased attention screening should not limited who aware having contracted but extended entire population.

Language: Английский

Citations

15
Measurement of IFN-γ and IL-2 for the assessment of the cellular immunity against SARS-CoV-2 DOI Creative Commons
Guillem Safont, Raquel Villar-Hernández,

Daria Smalchuk

et al.

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Jan. 11, 2024

The study of specific T-cell responses against SARS-CoV-2 is important for understanding long-term immunity and infection management. aim this was to assess the dual IFN-γ IL-2 detection, using a fluorescence ELISPOT, in patients undergoing acute disease, during convalescence, after vaccination. We also evaluated humoral response compared with T-cells correlating both types responses, increase number detection. Blood samples were drawn from COVID-19 convalescent individuals classified according disease severity; unvaccinated vaccinated uninfected individuals. IgGs Spike nucleocapsid, IgMs neutralizing antibodies analyzed. Our results show that combination increases detection (p = 0.023). In addition, can be useful biomarker monitoring severe patients, as our indicate those poor outcome have lower levels cytokine. some cases, lack cellular compensated by antibodies, confirming role immune infection, their detections. summary, IFN-γ/IL-2 promising characterizing assessing immunization status, helping patient

Language: Английский

Citations

12
Adverse effects following anti–COVID-19 vaccination with mRNA-based BNT162b2 are alleviated by altering the route of administration and correlate with baseline enrichment of T and NK cell genes DOI Creative Commons
Ayesa Syenina, Esther S. Gan,

Justin Z. N. Toh

et al.

PLoS Biology, Journal Year: 2022, Volume and Issue: 20(5), P. e3001643 - e3001643

Published: May 31, 2022

Ensuring high vaccination and even booster coverage is critical in preventing severe Coronavirus Disease 2019 (COVID-19). Among the various COVID-19 vaccines currently use, mRNA have shown remarkable effectiveness. However, systemic adverse events (AEs), such as postvaccination fatigue, are prevalent following vaccination, underpinnings of which not understood. Herein, we found that higher baseline expression genes related to T NK cell exhaustion suppression were positively correlated with development moderately fatigue after Pfizer-BioNTech BNT162b2 vaccination; increased associated reacted greater levels innate immune activation at 1 day postvaccination. We further found, a mouse model, altering route from intramuscular (i.m.) subcutaneous (s.c.) could lessen pro-inflammatory response correspondingly extent AEs; humoral was compromised. Instead, it possible s.c. improve cytotoxic CD8 T-cell responses vaccination. Our findings thus provide glimpse molecular basis suggest readily translatable solution minimize AEs.

Language: Английский

Citations

31