Nociplastic pain is the fourth category of pain defined in recent years. It is a pain arising from altered nociception, despite the lack of clear evidence of actual or threatened tissue damage that causes activation of peripheral nociceptors nor evidence for disease or lesion of the somatosensory system causing the pain. This type of pain is usually multifocal, more diffuse or intense than expected and it is usually associated with other central nervous system-derived symptoms, such as fatigue, sleep, memory, and mood problems. It can occur in isolation or as part of a mixed-pain state in combination with ongoing nociceptive or neuropathic pain. It is associated with increased social and sanitary costs due to the difficulty of adequately treating it. Its pathogenesis is still poorly understood, even if a mounting body of evidence suggests a pivotal role in inflammation and immunity, which may be triggered by an infection and/or a trauma. This narrative review aims to summarise the current knowledge about the interplay of the immune system and nociplastic pathways activation and amplification. The challenge for the future will be to identify the exact role of inflammation and immunity, the cause of this activation, and its link to other pathogenetic factors of nociplastic pain, such as diet or microbiota alteration, social and phycological factors, together with a genetic and epigenetic predisposition.

Aim: Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer-related mortality and is characterized by T-cell exhaustion, particularly in effector CD8+ T-cells. This exhaustion, driven by persistent immunosuppressive signals in the tumor microenvironment, impairs immune function and hinders effective immunotherapy. This study aimed to identify key exhaustion-related marker genes in CD8+ T-cells linked to PDAC and assess the potential of repurposing anti-inflammatory drugs to counteract T-cell exhaustion and enhance immune responses against PDAC. Methods: We employed a multi-omics approach, integrating single-cell RNA sequencing data with whole genome sequencing to identify dysregulated exhaustion-related immune markers in CD8+ T-cells in PDAC. We examined gene expression profiles and conducted functional enrichment analysis to evaluate their roles in immune exhaustion. We analyzed mutations in the shortlisted biomarkers from The Cancer Genome Atlas (TCGA) and performed in silico mutational analysis using Maestro to evaluate the impact of an IL7R mutation (K110N) on protein function. Virtual screening using a deep learning framework, GNINA, explored the inhibitory features of the anti-inflammatory drugs oxaprozin and celecoxib on IL7R. Results: Key dysregulated exhaustion-related immune markers were identified including PRF1, GZMA, CD8A, CD3D, NKG7, IL7R, and IL2RG. Pathway enrichment analysis indicated significant involvement in T-cell receptor signaling, Th1 and Th2 differentiation, and Th17 differentiation pathways, correlating with reported poor survival outcomes in PDAC patients. Mutational analysis of IL7R revealed a likely pathogenic mutation (K110N) located in the IL-7Ralpha fibronectin type III domain. Drug repurposing of oxaprozin and celecoxib showed favorable binding interactions with both wild and mutant IL7R proteins. Conclusions: The K110N mutation, despite not causing significant structural changes, may impact T-cell and B-cell homeostasis and development. Our findings suggest that oxaprozin and celecoxib could effectively inhibit T-cell exhaustion through favorable interactions with IL7R. Further clinical studies are necessary to validate the therapeutic potential of these anti-inflammatory drugs in enhancing immune responses in pancreatic cancer.

Aim: This study aims to identify the factors affecting the formation of neutralizing antibodies (NAbs) in healthy adults four weeks post-COVID-19 vaccination. Methods: A cross-sectional study was conducted among mass vaccination attendees using inactivated CoronaVac. Collected the peripheral blood serum four weeks following the second vaccine dose. Forty-four adults aged 26–85 were split into two groups based on age (≤ 60 years and > 60 years) and BMI (non-obese ≤ 25 kg/m2 and obese > 25 kg/m2). Variables like age, gender, BMI, and the presence of comorbidities were recorded. CD4/CD8 ratio and vitamin D levels were examined for their influence on NAbs formation. NAbs were measured using ELISA, T-cells via flow cytometry, and vitamin D through radioimmunoassay. Descriptive data analysis was performed as mean ± standard deviation to show the characteristics of the sample. Students’ t-tests and multivariate and univariate regression analyses were used to evaluate the data. Results: Significant variations in NAbs levels were observed with age (P = 0.013), BMI (P = 0.004), and comorbidities (P = 0.034). The elderly demonstrated higher NAb levels, potentially due to the high vitamin D levels compared to the adult group. The vitamin D levels strongly correlated with NAb titer (P < 0.001; R = 0.843). A collective correlation was found between NAb levels and the factors of age, BMI, and CD4/CD8 ratio (P = 0.033). A negative correlation existed between BMI and NAb levels (P = 0.018; R = –0.356) and between age and the CD4/CD8 ratio (P = 0.440; R = –0.119), but age alone did not correlate with NAb titer. Conclusions: Age, BMI, CD4/CD8 ratio, and comorbidities influence the production of post-vaccination NAbs. Sufficient vitamin D levels in the elderly significantly boost post-vaccination NAb levels. Maintaining a healthy body weight is also vital, as studies have revealed a significant and negative correlation between BMI and the level of NAbs, suggesting a possible need for adjusted vaccine doses in obese individuals.

Aim: Immunization with meningococcal vaccine (MV) is the most effective measure to control and prevent the transmission of meningococcal infections. In this study, in order to support the appropriate use of various MVs in the prevention of meningococcal meningitis (MM), the effects of MVs, especially single-dose and inter-booster administered, on inflammatory parameters in < 5-year-old children were investigated. Methods: A total of 464 healthy children were included in this study. The data of those who received the first 2 doses at 2-month intervals and the next dose between 8–12 months were included. Nimenrix® (Pfizer) administered as a single dose to children from 12 months of age. Bexsero® (GSK) was administered as 2 + 1 doses under 2 years of age and 2 doses 2 months apart over 2 years of age. Neutrophil, lymphocyte, monocyte, platelet counts, C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR), derived NLR (dNLR), platelet-to-lymphocyte ratio (PLR), systemic inflammation response index (SIR-I), and systemic immune inflammation index (SII) were evaluated. Results: Of the 464 participants, 58.2% were male, with a mean age of 3.81 years, and both sex ratios and ages were similar across the Nimenrix and Bexsero groups. The laboratory and inflammatory parameters of the two vaccine groups were similar. In both vaccine groups, changes in laboratory parameters before and 3-months after vaccination were similar. The changes in laboratory parameters over time between vaccine groups and their interactions were not significant. Conclusions: The NLR, dNLR, PLR, SIR-I, and SII are useful biomarkers indicating the inflammatory response of Nimenrix and Bexsero vaccines. Inflammatory markers can be used as both a safety endpoint and a protection endpoint for MVs (Nimenrix and Bexsero). However, further studies involving larger patient cohorts as well as detailed laboratory data on specific markers of inflammation are needed to draw comprehensive conclusions regarding the inflammatory response following vaccination.

Coronavirus disease 2019 (COVID-19) infected individuals showed either mild symptoms or were paucisymptomatic, with severe impact on human health, revealing heightened risk and direct effects on health. Among various factors contributing to complications, bacterial and fungal co-infection remains very common and is highly lethal. This narrative review aims to focus on the collective role of gut microbiota and mycobiota in COVID-19. Fungal infection has been identified as a key risk factor for the spread of COVID-19 and mortality. Gut mycobiomes diversity and abundance also vary due to the different types of SARS-CoV-2 variant infection. Their cross-talk plays a vital role in immune regulation and disease severity, with an emphasis on understanding the altered condition as a predictive marker. On the other hand, the gut microbiome is well known for shaping metabolic functions, generating immune responses, and deciphering the signal to decide the healthy state and disease condition of an individual. Immune response during COVID-19 infection was also linked with metabolites produced by the gut microflora, specifically amino acids, sugar metabolites, and neurotransmitters. The cross-talk between gut microbiota and gut mycobiota for clinical implications in terms of early detection, identification of the disease severity, and even therapeutic alternatives will open newer avenues. A deep dive understanding of the cross-talk between the microbiome and mycobiome, and their role in immune response will take scientific discovery knowledge to develop gut-targeted safe therapeutic approaches in the form of FMT (fecal microbiota transplantation) probiotics, peptides, antibacterial, and antifungal metabolites. Overall cross-talk and immune interplay are critical determinants of host immunity, providing insights into their role and key take home lessons for better management of crisis in the future.

Wound healing is an area of growing importance in the healthcare field, especially chronic wounds associated with comorbidities like diabetes mellitus (DM), hypoxic stress, obesity, and malnutrition. Chronic wounds significantly increase healthcare costs and reduce patients’ quality of life. Cytokines are a promising therapeutic target, as they regulate all stages of wound healing, and dysfunction in cytokine production can cause inflammatory non-healing wounds. Interleukin-1 (IL-1), IL-2, IL-6, IL-8, and tumour necrosis factor-α (TNF-α) facilitate leukocyte recruitment and clear dead cells during the initial inflammation stage while transforming growth factor-β (TGF-β), IL-4, and IL-13 inhibit inflammation and stimulate proliferation of fibroblasts to begin extracellular matrix (ECM) deposition. Given the complexity of cytokine interactions and their diverse cellular targets, a comprehensive understanding of these signaling pathways is crucial. This review examines the multifaceted roles of cytokines in wound healing and discusses recent advancements in the therapeutic application of cytokine modulation for improved wound care outcomes. Despite significant advancements in improving the specificity of cytokine therapies, further research is needed to focus on targeting downstream signaling pathways or specific receptors to minimize the adverse effects associated with these treatments.