The β-NGF/TrkA Signalling Pathway Is Associated With the Production of Anti-Nucleoprotein IgG in Convalescent COVID-19

BackgroundThe presentation of SARS-CoV-2 infection varies from asymptomatic to severe COVID-19. Similarly, high variability in the presence, titre and duration of specific antibodies has been reported. While some host factors determining these differences, such as age and ethnicity have been identified, the underlying molecular mechanisms underpinning these differences remain poorly defined.MethodsWe analysed serum and PBMC from 17 subjects with a previous PCR-confirmed SARS-CoV-2 infection and 10 unexposed volunteers following the first wave of the pandemic, in the UK. Anti-NP IgG and neutralising antibodies were measured, as well as a panel of infection and inflammation related cytokines. The virus-specific T cell response was determined by IFN-γ ELISPOT and flow cytometry after overnight incubation of PBMCs with pools of selected SARS-CoV-2 specific peptides.ResultsSeven of 17 convalescent subjects had undetectable levels of anti-NP IgG, and a positive correlation was shown between anti-NP IgG levels and the titre of neutralising antibodies (IC50). In contrast, a discrepancy was noted between antibody levels and T cell IFN-γ production by ELISpot following stimulation with specific peptides. Among the analysed cytokines, β-NGF and IL-1α levels were significantly different between anti-NP positive and negative subjects, and only β-NGF significantly correlated with anti-NP positivity. Interestingly, CD4+ T cells of anti-NP negative subjects expressed lower amounts of the β-NGF-specific receptor TrkA.ConclusionsOur results suggest that the β-NGF/TrkA signalling pathway is associated with the production of anti-NP specific antibody in mild SARS-CoV-2 infection and the mechanistic regulation of this pathway in COVID-19 requires further investigation.

Oxylipin metabolism is controlled by mitochondrial β-oxidation during bacterial inflammation

Oxylipins are potent biological mediators requiring strict control, but how they are removed en masse during infection and inflammation is unknown. Here we show that lipopolysaccharide (LPS) dynamically enhances oxylipin removal via mitochondrial β-oxidation. Specifically, genetic or pharmacological targeting of carnitine palmitoyl transferase 1 (CPT1), a mitochondrial importer of fatty acids, reveal that many oxylipins are removed by this protein during inflammation in vitro and in vivo. Using stable isotope-tracing lipidomics, we find secretion-reuptake recycling for 12-HETE and its intermediate metabolites. Meanwhile, oxylipin β-oxidation is uncoupled from oxidative phosphorylation, thus not contributing to energy generation. Testing for genetic control checkpoints, transcriptional interrogation of human neonatal sepsis finds upregulation of many genes involved in mitochondrial removal of long-chain fatty acyls, such as ACSL1,3,4, ACADVL, CPT1B, CPT2 and HADHB. Also, ACSL1/Acsl1 upregulation is consistently observed following the treatment of human/murine macrophages with LPS and IFN-γ. Last, dampening oxylipin levels by β-oxidation is suggested to impact on their regulation of leukocyte functions. In summary, we propose mitochondrial β-oxidation as a regulatory metabolic checkpoint for oxylipins during inflammation.

Oxidative ornithine metabolism supports non-inflammatory C. difficile colonization

The enteric pathogen Clostridioides difficile (Cd) is responsible for a toxin-mediated infection that causes more than 200,000 recorded hospitalizations and 13,000 deaths in the United States every year1. However, Cd can colonize the gut in the absence of disease symptoms. Prevalence of asymptomatic colonization by toxigenic Cd in healthy populations is high; asymptomatic carriers are at increased risk of infection compared to noncolonized individuals and may be a reservoir for transmission of Cd infection2,3. Elucidating the molecular mechanisms by which Cd persists in the absence of disease is necessary for understanding pathogenesis and developing refined therapeutic strategies. Here, we show with gut microbiome metatranscriptomic analysis that mice recalcitrant to Cd infection and inflammation exhibit increased community-wide expression of arginine and ornithine metabolic pathways. To query Cd metabolism specifically, we leverage RNA sequencing in gnotobiotic mice infected with two wild-type strains (630 and R20291) and isogenic toxin-deficient mutants of these strains to differentiate inflammation-dependent versus -independent transcriptional states. A single operon encoding oxidative ornithine degradation is consistently upregulated across non-toxigenic Cd strains. Combining untargeted and targeted metabolomics with bacterial and host genetics, we demonstrate that both diet- and host-derived sources of ornithine provide a competitive advantage to Cd, suggesting a mechanism for Cd persistence within a non-inflammatory, healthy gut.

Epidemiology, etiology, and treatment of denture stomatitis

Multiple factors are involved in the pathogenesis of denture stomatitis, which increases the risk of tissue infection and inflammation. These factors include poor oral hygiene, trauma secondary to poorly fitting prostheses, resin porosity, and bacterial plaque accumulation. Our present review discusses the epidemiology, etiology, and treatment of denture stomatitis based on data from current studies in the literature. The prevalence of denture stomatitis is significantly variable among the different studies, as previously discussed. However, the cumulative incidence of denture stomatitis among their participants ranged between 17-77%. These hugely variable rates have been attributed to the nature of data collection, diagnostic criteria, sample size, and patient demographics. Studies also show that the condition is more prevalent among elderly females. However, not many studies have reported this correlation, indicating the need for future studies. Candida albicans infection is the primary parameter in the etiology and pathogenesis of the condition. However, other factors related to the patient (like status of immunological response) and dentures (like hygiene) were also reported. Therefore, the management of denture stomatitis should be based on applying adequate interventions. Besides, using antifungal medications is also necessary to eradicate organism.

Effect of vitamin D on infection and inflammation in patients with cystic fibrosis: a systematic review and meta-analysis

Background Cystic fibrosis (CF) is a genetic disorder in which the respiratory system gets clogged with mucus leads to progressive lung damage. There is no known cure for CF but several treatments to manage symptoms and reduce complications. Vitamin D deficiency is common in CF associated with increased infection and inflammation. This systematic review and meta analysis will evaluate the effectiveness of vitamin D treatment in reducing respiratory tract infection and inflammation in patients with CF. Methods Randomized and quasi randomised studies in CF patients with control groups will be identified. The antibacterial activity of vitamin D supplementation will help in reducing respiratory tract infection and inflammation in CF. Overall effects of vitamin D in terms of infection and inflammatory markers such as C reactive protein, inflammatory cytokine interleukin (IL)6, IL8, IL17, IL23, antimicrobial peptide (LL37), lung function defined by forced expiratory volume in 1 second (FEV1)%, other assessed respiratory parameters will be calculated using random-effect models. Study quality will be assessed using RoB 2, A revised Cochrane Risk of Bias tool for randomised trials. The overall quality of evidence for each outcome will be summarised according to the Grading of Recommendations Assessment, Development, and Evaluations (GRADE) framework.

The Role of Methyl Donors of the Methionine Cycle in Gastrointestinal Infection and Inflammation

Vitamin deficiency is well known to contribute to disease development in both humans and other animals. Nonetheless, truly understanding the role of vitamins in human biology requires more than identifying their deficiencies. Discerning the mechanisms by which vitamins participate in health is necessary to assess risk factors, diagnostics, and treatment options for deficiency in a clinical setting. For researchers, the absence of a vitamin may be used as a tool to understand the importance of the metabolic pathways in which it participates. This review aims to explore the current understanding of the complex relationship between the methyl donating vitamins folate and cobalamin (B12), the universal methyl donor S-adenosyl-L-methionine (SAM), and inflammatory processes in human disease. First, it outlines the process of single-carbon metabolism in the generation of first methionine and subsequently SAM. Following this, established relationships between folate, B12, and SAM in varying bodily tissues are discussed, with special attention given to their effects on gut inflammation.

Update sul management e trattamento del paziente con lesioni cutanee croniche

Le lesioni da decubito, le ulcere vascolari e il piede diabetico rappresentano le lesioni cutanee croniche maggiormente diffuse in età geriatrica. La lesione cutanea cronica presenta un elevato rischio infettivo ed un management complesso che richiede terapie mirate ed un iter di trattamento specifico. Il metodo TIME (Tissue management control of Infection and inflammation Moisture imbalance advancement of the Epithelial edge of the wound), costituisce il gold standard per il trattamento delle lesioni cutanee croniche poiché consente di controllare l’infezione e il grado di macerazione della ferita anche nei margini epiteliali. La soluzione di ipoclorito di sodio alla concentrazione dello 0,05%, oggetto di numerosi studi in letteratura, grazie ad un ampio spettro germicida ed alla sua elevata compatibilità tissutale rappresenta il metodo di disinfezione d’elezione per il trattamento delle lesioni cutanee croniche. La qualità di vita (Quality of Life, QoL) di un paziente affetto da lesione cutanea cronica può essere fortemente compromessa. La formazione di un team sanitario multidisciplinare per la gestione del patient journey può favorire il percorso di guarigione, facilitare la gestione della lesione nella quotidianità e migliorare la QoL del paziente. La telemedicina spicca tra le modalità innovative di gestione del wound care sperimentate da un’equipe di specialisti del territorio ligure negli ultimi mesi a seguito della pandemia COVID-19. La pratica della telemedicina si è rivelata particolarmente utile nel follow up della lesione cronica a fronte di un adeguato impiego di strumenti tecnologici che permettano un’elevata qualità di immagini.

Identifying new molecular players in extracellular proteostasis

Proteostasis refers to a delicately tuned balance between the processes of protein synthesis, folding, localization, and the degradation of proteins found inside and outside cells. Our understanding of extracellular proteostasis is rather limited and largely restricted to knowledge of 11 currently established extracellular chaperones (ECs). This review will briefly outline what is known of the established ECs, before moving on to discuss experimental strategies used to identify new members of this growing family, and an examination of a group of putative new ECs identified using one of these approaches. An observation that emerges from an analysis of the expanding number of ECs is that all of these proteins are multifunctional. Strikingly, the armory of activities each possess uniquely suit them as a group to act together at sites of tissue damage, infection, and inflammation to restore homeostasis. Lastly, we highlight outstanding questions to guide future research in this field.