Journal of investigative medicine : the official publication of the American Federation for Clinical Research
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Observational Study
Long COVID following mild SARS-CoV-2 infection: characteristic T cell alterations and response to antihistamines.
Long COVID is characterized by the emergence of multiple debilitating symptoms following SARS-CoV-2 infection. Its etiology is unclear and it often follows a mild acute illness. Anecdotal reports of gradual clinical responses to histamine receptor antagonists (HRAs) suggest a histamine-dependent mechanism that is distinct from anaphylaxis, possibly mediated by T cells, which are also regulated by histamine. ⋯ Symptoms were quantified using a structured questionnaire and T cell subsets enumerated in a standard diagnostic assay. Patients with long-COVID had reduced CD4+ and CD8+ effector memory (EM) cell numbers and increased PD-1 (programmed cell death protein 1) expression on central memory (CM) cells, whereas the asymptomatic participants had reduced CD8+ EM cells only and increased CD28 expression on CM cells. 72% of patients with long COVID who received HRA reported clinical improvement, although T cell profiling did not clearly distinguish those who responded to HRA. This study demonstrates that T cell perturbations persist for several months after mild COVID-19 and are associated with long COVID symptoms.
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Carboxyhemoglobin (CO-Hb) can be endogenously formed in the presence of oxidative stress and may be elevated in inflammatory lung disease. There is lack of evidence of its relationship with the development of bronchopulmonary dysplasia (BPD) in extremely low birthweight (ELBW) infants. The objective of the study is to evaluate the relationship between blood CO-Hb levels in the first 14 days of life (DOL) in ELBW infants and the development of BPD at 36 weeks postmenstrual age (PMA). ⋯ Receiver operator curve was used to evaluate the ability of the median fraction of inspired oxygen (FiO2) level used at DOL 11-14 in discriminating absent to mild BPD versus moderate to severe BPD. 58 ELBW infants were included in the study. 24 (41%) were diagnosed with moderate to severe BPD, while 34 (59%) were diagnosed with no to mild BPD. Severity of BPD was fairly discriminated by FiO2 at DOL 11-14, but not with CO-Hb levels at any point within the first 14 DOL. The role and mechanism of CO-Hb production in this population need to be further studied.
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Maslinic acid (MA), a pentacyclic triterpenoid, has been reported to exert broad pharmacological properties. However, it is still unclear whether MA exhibits protective effects against ischemia/reperfusion (I/R) injury. Herein, we aimed to investigate the effects of MA on I/R injury and its underlying mechanisms. ⋯ Interestingly, treatment with MA (20 mg/kg) also regulated myocardial apoptosis and inhibited oxidative-stress in left ventricular tissue. Mechanistic studies demonstrated that MA upregulated SIRT1 and AMPK phosphorylation in the left ventricular tissue. In summary, MA exerted protective effects against the impairments of cardiac function in I/R injury rats by the regulation of SIRT1/AMPK signaling pathways.
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Short-chain fatty acids (SCFAs), the end products of fermentation carried out by the intestinal microbiota, were demonstrated to produce anti-oxidant and anti-inflammatory effects. Butyrate, part of the SCFAs, also shows the same effect. Renal ischemia/reperfusion (I/R) injury commonly occurs in renal transplantation and is often accompanied by oxidative stresses and inflammatory responses. ⋯ Butyrate expressed like SCFAs. In this study, we demonstrated that butyrate increased with the recovery of renal function after renal transplantation. Most importantly, butyrate treatments alleviated the renal damages caused by I/R via the upregulation of intracellular oxidant stress and inflammations.