First insight about the ability of specific glycerophospholipids to discriminate non-small cell lung cancer subtypes.

Introduction: Discrimination between adenocarcinoma (ADC) and squamous cell carcinoma (SCC) subtypes in non-small cell lung cancer (NSCLC) patients is a significant challenge in oncology. Lipidomics analysis provides a promising approach for this differentiation. Methods: In an accompanying paper, we explored oxPCs levels in a cohort of 200 NSCLC patients. In this research, we utilized liquid chromatography coupled with mass spectrometry (LC-MS) to analyze the lipidomics profile of matching tissue and plasma samples from 25 NSCLC patients, comprising 11 ADC and 14 SCC cases. This study builds upon our previous findings, which highlighted the elevation of oxidised phosphatidylcholines (oxPCs) in NSCLC patients. Results: We identified eight lipid biomarkers that effectively differentiate between ADC and SCC subtypes using an untargeted approach. Notably, we observed a significant increase in plasma LPA 20:4, LPA 18:1, and LPA 18:2 levels in the ADC group compared to the SCC group. Conversely, tumour PC 16:0/18:2, PC 16:0/4:0; CHO, and plasma PC 16:0/18:2; OH, PC 18:0/20:4; OH, PC 16:0/20:4; OOH levels were significantly higher in the ADC group. Discussion: Our study is the first to report that plasma LPA levels can distinguish between ADC and SCC patients in NSCLC, suggesting a potential role for LPAs in NSCLC subtyping. This finding warrants further investigation into the mechanisms underlying these differences and their clinical implications.

Circulating serum miR-362-3p and miR-6721-5p as potential biomarkers for classification patients with adult-type diffuse glioma.

According to the fifth edition of the WHO Classification of Tumours of the Central Nervous System (CNS) published in 2021, grade 4 gliomas classification includes IDH-mutant astrocytomas and wild-type IDH glioblastomas. Unfortunately, despite precision oncology development, the prognosis for patients with grade 4 glioma remains poor, indicating an urgent need for better diagnostic and therapeutic strategies. Circulating miRNAs besides being important regulators of cancer development could serve as promising diagnostic biomarkers for patients with grade 4 glioma. Here, we propose a two-miRNA miR-362-3p and miR-6721-5p screening signature for serum for non-invasive classification of identified glioma cases into the highest-grade 4 and lower-grade gliomas. A total of 102 samples were included in this study, comprising 78 grade 4 glioma cases and 24 grade 2-3 glioma subjects. Using the NanoString platform, seven miRNAs were identified as differentially expressed (DE), which was subsequently confirmed via RT-qPCR analysis. Next, numerous combinations of DE miRNAs were employed to develop classification models. The dual panel of miR-362-3p and miR-6721-5p displayed the highest diagnostic value to differentiate grade 4 patients and lower grade cases with an AUC of 0.867. Additionally, this signature also had a high AUC = 0.854 in the verification cohorts by RT-qPCR and an AUC = 0.842 using external data from the GEO public database. The functional annotation analyses of predicted DE miRNA target genes showed their primary involvement in the STAT3 and HIF-1 signalling pathways and the signalling pathway of pluripotency of stem cells and glioblastoma-related pathways. For additional exploration of miRNA expression patterns correlated with glioma, we performed the Weighted Gene-Co Expression Network Analysis (WGCNA). We showed that the modules most associated with glioma grade contained as many as six DE miRNAs. In conclusion, this study presents the first evidence of serum miRNA expression profiling in adult-type diffuse glioma using a classification based on the WHO 2021 guidelines. We expect that the discovered dual miR-362-3p and miR-6721-5p signatures have the potential to be utilised for grading gliomas in clinical applications.

Effects of Combinatory In Vitro Treatment with Immune Checkpoint Inhibitors and Cytarabine on the Anti-Cancer Immune Microenvironment in De Novo AML Patients.

Despite substantial progress in the diagnostic and therapeutic procedures, acute myeloid leukaemia (AML) still constitutes a significant problem for patients suffering from its relapses. A comprehensive knowledge of the disease's molecular background has led to the development of targeted therapies, including immune checkpoint inhibitors, and demonstrated beneficial effects on several types of cancer. Here, we aimed to assess in vitro the potential of the immune checkpoint blockage for supporting anti-cancer responses to the AML backbone therapy with cytarabine. PBMCs of AML patients were collected at admission and, following the therapy, eight complete remission (CR) and eight non-responders (NR) subjects were selected. We assessed the effects of the in vitro treatment of the cells with cytarabine and the immune checkpoint inhibitors: anti-CTLA-4, anti-PD-1, anti-PD-L1. The study protocol allowed us to evaluate the viability of the cancer and the immune cells, proliferation status, phenotype, and cytokine release. Anti-PD-L1 antibodies were found to exert the most beneficial effect on the activation of T cells, with a concomitant regulation of the immune balance through Treg induction. There was no direct influence on the blast cells; however, the modulation of the PD-1/PD-L1 axis supported the expansion of lymphocytes. Changes in the response between CR and NR patients might result from the differential expression of PD-1 and PD-L1, with lower levels in the latter group. The tested blockers appear to support the anti-cancer immune responses rather than directly improve the effects of cytarabine. In conclusion, checkpoint proteins' modulators might improve the anti-cancer responses in the tumour environment.

Metabolomic profile of acute myeloid leukaemia parallels of prognosis and response to therapy.

The heterogeneity of acute myeloid leukemia (AML), a complex hematological malignancy, is caused by mutations in myeloid cells affecting their differentiation and proliferation. Thus, various cytogenetic alterations in AML cells may be characterized by a unique metabolome and require different treatment approaches. In this study, we performed untargeted metabolomics to assess metabolomics differences between AML patients and healthy controls, AML patients with different treatment outcomes, AML patients in different risk groups based on the 2017 European LeukemiaNet (ELN) recommendations for the diagnosis and management of AML, AML patients with and without FLT3-ITD mutation, and a comparison between patients with FLT3-ITD, CBF-AML (Core binding factor acute myelogenous leukemia), and MLL AML (mixed-lineage leukemia gene) in comparison to control subjects. Analyses were performed in serum samples using liquid chromatography coupled with mass spectrometry (LC-MS). The obtained metabolomics profiles exhibited many alterations in glycerophospholipid and sphingolipid metabolism and allowed us to propose biomarkers based on each of the above assessments as an aid for diagnosis and eventual classification, allowing physicians to choose the best-suited treatment approach. These results highlight the application of LC-MS-based metabolomics of serum samples as an aid in diagnostics and a potential minimally invasive prognostic tool for identifying various cytogenetic and treatment outcomes of AML.

Mesenchymal stem cells under epigenetic control - the role of epigenetic machinery in fate decision and functional properties.

Mesenchymal stem cells (mesenchymal stromal cells, MSC) are multipotent stem cells that can differentiate into cells of at least three mesodermal lineages, namely adipocytes, osteoblasts, and chondrocytes, and have potent immunomodulatory properties. Epigenetic modifications are critical regulators of gene expression and cellular differentiation of mesenchymal stem cells (MSCs). Epigenetic machinery controls MSC differentiation through direct modifications to DNA and histones. Understanding the role of epigenetic machinery in MSC is crucial for the development of effective cell-based therapies for degenerative and inflammatory diseases. In this review, we summarize the current understanding of the role of epigenetic control of MSC differentiation and immunomodulatory properties.

Identification of serum miR-1246 and miR-150-5p as novel diagnostic biomarkers for high-grade serous ovarian cancer.

Epithelial ovarian cancer (EOC) is one of the leading cancers in women, with high-grade serous ovarian cancer (HGSOC) being the most common and lethal subtype of this disease. A vast majority of HGSOC are diagnosed at the late stage of the disease when the treatment and total recovery chances are low. Thus, there is an urgent need for novel, more sensitive and specific methods for early and routine HGSOC clinical diagnosis. In this study, we performed miRNA expression profiling using the NanoString miRNA assay in 34 serum samples from patients with HGSOC and 36 healthy women. We identified 13 miRNAs that were differentially expressed (DE). For additional exploration of expression patterns correlated with HGSOC, we performed weighted gene co-expression network analysis (WGCNA). As a result, we showed that the module most correlated with tumour size, nodule and metastasis contained 8 DE miRNAs. The panel including miR-1246 and miR-150-5p was identified as a signature that could discriminate HGSOC patients with AUCs of 0.98 and 1 for the training and test sets, respectively. Furthermore, the above two-miRNA panel had an AUC = 0.946 in the verification cohorts of RT-qPCR data and an AUC = 0.895 using external data from the GEO public database. Thus, the model we developed has the potential to markedly improve the diagnosis of ovarian cancer.

The Association between Immune Checkpoint Proteins and Therapy Outcomes in Acute Myeloid Leukaemia Patients.

The development of novel drugs with different mechanisms of action has dramatically changed the treatment landscape of AML patients in recent years. Considering a significant dysregulation of the immune system, inhibitors of immune checkpoint (ICI) proteins provide a substantial therapeutic option for those subjects. However, use of ICI in haematological malignancies remains very limited, in contrast to their wide use in solid tumours. Here, we analysed expression patterns of the most promising selected checkpoint-based therapeutic targets in AML patients. Peripheral blood of 72 untreated AML patients was used for flow cytometric analysis. Expression of PD-1, PD-L1, CTLA-4, and B7-H3 was assessed within CD4+ (Th) lymphocytes and CD33+ blast cells. Patients were stratified based on therapy outcome and cytogenetic molecular risk. AML non-responders (NR) showed a higher frequency of PD-1 in Th cells compared to those with complete remission (CR). Reduced blast cell level of CTLA-4 was another factor differentiating CR from NR subjects. Elevated levels of PD-1 were associated with a trend for poorer patients' survival. Additionally, prognosis for AML patients was worse in case of a higher frequency of B7-H3 in Th lymphocytes. In summary, we showed the significance of selected ICI as outcome predictors in AML management. Further, multicentre studies are required for validation of those data.

Application of 18F-PSMA-1007 PET/MR Imaging in Early Biochemical Recurrence of Prostate Cancer: Results of a Prospective Study of 60 Patients with Very Low PSA Levels ≤ 0.5 ng/mL.

The use of 18F-PSMA-1007 and the role of PET/MR in the diagnosis of prostate cancer are not conclusively confirmed. There are reports indicating the potential pros and cons of using 18F-PSMA-1007 as well as the PET/MR technique in prostate cancer recurrence, but they are not yet included in the EAU guidelines. The aim of the study was to assess the effectiveness of 18F-PSMA-1007 PET/MR in detecting BCR lesions at very low PSA levels <0.5 ng/mL. METHODS: Sixty patients with BCR after radical prostatectomy (RP) with PSA ranged 0.1-0.5 ng/mL were enrolled in a prospective study. All patients underwent simultaneous whole-body and pelvic 18F-PSMA-1007 PET/MR. The obtained results were verified by 12-month follow-up. RESULTS: Fifty-three lesions were detected in 45 patients with 75% detection rate. The mean PSA value was 0.31 ng/mL. Of all PSMA-positive foci, 91% were localized in the pelvis, and only 9% of lesions were located in the extrapelvic region. Local recurrences were detected in 29%, PSMA-positive lymph nodes were detected in 64% of patients and bone metastases lesions were detected in 7% of patients. CONCLUSIONS: 18F-PSMA-1007 PET/MR seems to be an excellent diagnostic tool in patients with early BCR with very low PSA levels, especially with dt PSA < 6 months. The synergistic effect of combining 18F-PSMA-1007 and whole-body PET/MR with precise multiparametric assessment of pelvic lesions is of particular benefit in early BCR.

Identification and subsequent validation of transcriptomic signature associated with metabolic status in endometrial cancer.

Aberrant metabolism has been identified as a main driver of cancer. Profiling of metabolism-related pathways in cancer furthers the understanding of tumor plasticity and identification of potential metabolic vulnerabilities. In this prospective controlled study, we established transcriptomic profiles of metabolism-related pathways in endometrial cancer (EC) using a novel method, NanoString nCounter Technology. Fifty-seven ECs and 30 normal endometrial specimens were studied using the NanoString Metabolic Panel, further validated by qRT-PCR with a very high similarity. Statistical analyses were by GraphPad PRISM and Weka software. The analysis identified 11 deregulated genes (FDR ≤ 0.05; |FC|≥ 1.5) in EC: SLC7A11; SLC7A5; RUNX1; LAMA4; COL6A3; PDK1; CCNA1; ENO1; PKM; NR2F1; and NAALAD2. Gene ontology showed direct association of these genes with 'central carbon metabolism (CCM) in cancer'. Thus, 'CCM in cancer' appears to create one of the main metabolic axes in EC. Further, transcriptomic data were functionally validated with drug repurposing on three EC cell lines, with several drug candidates suggested. These results lay the foundation for personalized therapeutic strategies in this cancer. Metabolic plasticity represents a promising diagnostic and therapeutic option in EC.

The influence of calcitriol and methylprednisolone on podocytes function in minimal change disease in vitro model.

Minimal change disease (MCD), considered one of the major causes of nephrotic syndrome, is a complex pathological condition with disturbances in podocytes' foot processes. Numerous studies suggested the essential role of vitamin D3 in maintaining proper glomerulus function. However, the data on direct potential of that compound in reference to podocytes are scarce. Thus, here we assessed the influence of calcitriol (active vitamin D3) on podocyte function, apart from commonly used steroids (methylprednisolone). CIHP-1 podocyte cell line was used to implement the LPS-PAN-induced MCD in vitro model. Viability, podocyte-related slit diaphragm proteins, morphology, function as a barrier was evaluated using flow cytometry, RT-PCR, confocal microscopy, and TEER analysis. Calcitriol or methylprednisolone did not affect cell viability. Podocyte-related proteins demonstrated different responses to in vitro treatment compared to previously reported changes in total glomeruli. Podocyte morphology was partially restored in the presence of the tested compounds. In addition, TEER analysis revealed improvement of LPS-PAN-induced cells' function as a barrier when vitamin D3 or steroid was used. In conclusion, a significant potential for modulation of MCD in vitro model podocytes with calcitriol or selected steroids was reported. Further studies on vitamin D3 in context of podocyte-related phenomenon accompanying MCD are of great importance.

Significance of Th17 and Treg in Treatment Efficacy and Outcome in Pediatric Acute Lymphoblastic Leukemia.

Acute lymphoblastic leukemia represents a malignant proliferation of lymphoid cells blocked at an early stage of cell differentiation. It is the most common cancer occurring in children. Despite favorable prognosis, the survival rate of patients with poor treatment response or relapse remains dismal. The interaction between leukemic cells and the tumor immune microenvironment is pivotal in mediating tumor progression. In this study we evaluated associations between Treg and Th17 lymphocytes and the clinical presentation of ALL pediatric patients to validate their value in monitoring treatment outcome. The peripheral blood and bone marrow aspirates from 35 pediatric patients with ALL and 48 healthy control subjects were selected for the experiment. We demonstrated the numbers of Th17 lymphocytes and Tregs were increased in the bone marrow of ALL patients at the moment of diagnosis compared to the healthy control group, with the latter significantly decreasing during the course of ALL treatment. Patients with lower Th17 were found to demonstrate higher risk of blasts prevalence in bone marrow at day 33. ALL patients with lower WBC demonstrated higher frequency of Tregs. In summary, we identified a significant role of Th17 and Treg lymphocytes in ALL of pediatric patients and their contribution to disease-related parameters.

Effect of antiviral and immunomodulatory treatment on a cytokine profile in patients with COVID-19.

Background: The severity of COVID-19 is associated with an elevated level of a variety of inflammatory mediators. Increasing evidence suggests that the Th17 response contributes to the severity of COVID-19 pneumonia, whereas Th22 response plays a regulatory role in SARS-CoV-2 infection. Two main types of available COVID-19 treatments are antivirals and immunomodulatory drugs; however, their effect on a cytokine profile is yet to be determined. Methods: This study aim to analyse a cytokine profile in peripheral blood from patients with COVID-19 (n=44) undergoing antiviral or/and immunomodulatory treatment and healthy controls (n=20). Circulating CD4+ and CD8+ T cells and their intracellular expression of IL-17A and IL-22 were assessed by flow cytometry. Results: Initial results showed an overexpression of IL-17F, IL-17A, CCL5/RANTES, GM-CSF, IL-4, IL-10, CXCL-10/IP-10 and IL-6 in COVID-19 patients compared to healthy controls. Treatment with remdesivir resulted in a significant decline in concentrations of IL-6, IL-10, IFN-alpha and CXCL10/IP-10. Immunomodulatory treatment contributed to a significant downregulation of IL-10, IFN-alpha, CXCL10/IP-10 and B7-H3 as well as upregulation of IL-22 and IL-1 beta. A combination of an antiviral and immunomodulatory treatment resulted in a significant decrease in IL-17F, IL-10, IFN-alpha, CXCL10/IP-10 and B7-H3 levels as well as an increase in IL-17A and IL-1 beta. We found significantly higher percentage of both CD4+ and CD8+ T cells producing IL-17A and CD4+ T cells producing IL-22 in patients with COVID-19. Conclusion: Administration of antiviral or/and immunomodulatory treatment resulted in a significant downregulation of pro-inflammatory cytokine expression and an upregulation of T cell absolute counts in most cases, thus showing effectiveness of treatment in COVID-19. SARS-CoV-2 infection induced cytokine overexpression in hospitalized patients with COVID-19 as well as lymphopenia, particularly a decrease in CD4+ and CD8+ T cell counts. Moreover, despite the reduced counts of CD4+ and CD8+ T cells, both subsets showed overactivation and increased expression of IL-17A and IL-22, thus targeting Th17 response might alleviate inflammatory response in severe disease.

A comparison of different machine-learning techniques for the selection of a panel of metabolites allowing early detection of brain tumors.

Metabolomics combined with machine learning methods (MLMs), is a powerful tool for searching novel diagnostic panels. This study was intended to use targeted plasma metabolomics and advanced MLMs to develop strategies for diagnosing brain tumors. Measurement of 188 metabolites was performed on plasma samples collected from 95 patients with gliomas (grade I-IV), 70 with meningioma, and 71 healthy individuals as a control group. Four predictive models to diagnose glioma were prepared using 10 MLMs and a conventional approach. Based on the cross-validation results of the created models, the F1-scores were calculated, then obtained values were compared. Subsequently, the best algorithm was applied to perform five comparisons involving gliomas, meningiomas, and controls. The best results were obtained using the newly developed hybrid evolutionary heterogeneous decision tree (EvoHDTree) algorithm, which was validated using Leave-One-Out Cross-Validation, resulting in an F1-score for all comparisons in the range of 0.476-0.948 and the area under the ROC curves ranging from 0.660 to 0.873. Brain tumor diagnostic panels were constructed with unique metabolites, which reduces the likelihood of misdiagnosis. This study proposes a novel interdisciplinary method for brain tumor diagnosis based on metabolomics and EvoHDTree, exhibiting significant predictive coefficients.

Alpha-Synuclein mRNA Level Found Dependent on L444P Variant in Carriers and Gaucher Disease Patients on Enzyme Replacement Therapy.

Gaucher disease (GD) is the most frequent sphingolipidosis, caused by biallelic pathogenic variants in the GBA1 gene encoding for ß-glucocerebrosidase (GCase, E.C. 3.2.1.45). The condition is characterized by hepatosplenomegaly, hematological abnormalities, and bone disease in both non-neuronopathic type 1 (GD1) and neuronopathic type 3 (GD3). Interestingly, GBA1 variants were found to be one of the most important risk factors for the development of Parkinson's disease (PD) in GD1 patients. We performed a comprehensive study regarding the two most disease-specific biomarkers, glucosylsphingosine (Lyso-Gb1) and α-synuclein for GD and PD, respectively. A total of 65 patients with GD treated with ERT (47 GD1 patients and 18 GD3 patients), 19 GBA1 pathogenic variant carriers (including 10 L444P carriers), and 16 healthy subjects were involved in the study. Lyso-Gb1 was assessed by dried blood spot testing. The level of α-synuclein as an mRNA transcript, total, and oligomer protein concentration were measured with real-time PCR and ELISA, respectively. α-synuclein mRNA level was found significantly elevated in GD3 patients and L444P carriers. GD1 patients, along with GBA1 carriers of an unknown or unconfirmed variant, as well as healthy controls, have the same low level of α-synuclein mRNA. There was no correlation found between the level of α-synuclein mRNA and age in GD patients treated with ERT, whereas there was a positive correlation in L444P carriers.

Excessive BMI is associated with higher C-peptide level at recognition but also with its greater loss in two years clinical observation in children with new onset type 1 diabetes.

Introduction: The prevalence of obesity in general pediatric population increases without sparing children with T1D. We intended to find factors associated with the possibility of preserving endogenous insulin secretion in individuals with long-standing T1D. At onset, higher BMI is associated with higher C-peptide level, which may indicate to be one of the favorable factors involved in preserving residual ß-cell function. The study determines the influence of BMI on C-peptide secretion in children newly diagnosed with T1D in two years observation. Methods: We assessed the possible relationship between selected pro- and anti-inflammatory cytokines, body mass at recognition and ß-cell function status. 153 pediatric patients with newly diagnosed T1D were divided into quartiles according to BMI-SDS index. We separated a group consisted of patients with BMI-SDS >1. Participants were followed up for two years and examined for changes in body weight, HbA1c, and insulin requirement. C-peptide was assessed at baseline and after two years. We evaluated the patients' levels of selected inflammatory cytokines at baseline. Results: Subjects with higher BMI-SDS presented higher serum C-peptide levels and lower insulin requirements at diagnosis than children with lower body weight. The two-year follow-up showed that C-peptide levels of obese patients dropped more rapidly than in children with BMI-SDS within normal limits. The group with BMI-SDS >1 showed the greatest decrease in C-peptide level. Despite statistically insignificant differences in HbA1c at diagnosis between the study groups, in the fourth quartile and BMI-SDS >1 groups, HbA1c as well as insulin requirements increased after two years. The levels of cytokines varied the most between BMI-SDS <1 and BMI-SDS >1 groups and were significantly higher within BMI-SDS >1 group. Discussion: Higher BMI, associated with enhanced levels of inflammatory cytokines, relates to preservation of C-peptide at T1D recognition in children but is not beneficial in the long term. A decrease in C-peptide levels combined with an increase in insulin requirements and in HbA1c among patients with high BMI occur, which may indicate a negative effect of excessive body weight on the long term preservation of residual ß-cell function. The process seems to be mediated by inflammatory cytokines.

Rhinovirus-induced epithelial RIG-I inflammasome suppresses antiviral immunity and promotes inflammation in asthma and COVID-19.

Rhinoviruses and allergens, such as house dust mite are major agents responsible for asthma exacerbations. The influence of pre-existing airway inflammation on the infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is largely unknown. We analyse mechanisms of response to viral infection in experimental in vivo rhinovirus infection in healthy controls and patients with asthma, and in in vitro experiments with house dust mite, rhinovirus and SARS-CoV-2 in human primary airway epithelium. Here, we show that rhinovirus infection in patients with asthma leads to an excessive RIG-I inflammasome activation, which diminishes its accessibility for type I/III interferon responses, leading to their early functional impairment, delayed resolution, prolonged viral clearance and unresolved inflammation in vitro and in vivo. Pre-exposure to house dust mite augments this phenomenon by inflammasome priming and auxiliary inhibition of early type I/III interferon responses. Prior infection with rhinovirus followed by SARS-CoV-2 infection augments RIG-I inflammasome activation and epithelial inflammation. Timely inhibition of the epithelial RIG-I inflammasome may lead to more efficient viral clearance and lower the burden of rhinovirus and SARS-CoV-2 infections.

Plasma Gelsolin Enhances Phagocytosis of Candida auris by Human Neutrophils through Scavenger Receptor Class B.

In addition to its role as an actin-depolymerizing factor in the blood, plasma gelsolin (pGSN) binds bacterial molecules and stimulates the phagocytosis of bacteria by macrophages. Here, using an in vitro system, we assessed whether pGSN could also stimulate phagocytosis of the fungal pathogen Candida auris by human neutrophils. The extraordinary ability of C. auris to evade immune responses makes it particularly challenging to eradicate in immunocompromised patients. We demonstrate that pGSN significantly enhances C. auris uptake and intracellular killing. Stimulation of phagocytosis was accompanied by decreased neutrophil extracellular trap (NET) formation and reduced secretion of proinflammatory cytokines. Gene expression studies revealed pGSN-dependent upregulation of scavenger receptor class B (SR-B). Inhibition of SR-B using sulfosuccinimidyl oleate (SSO) and block lipid transport-1 (BLT-1) decreased the ability of pGSN to enhance phagocytosis, indicating that pGSN potentiates the immune response through an SR-B-dependent pathway. These results suggest that the response of the host's immune system during C. auris infection may be enhanced by the administration of recombinant pGSN. IMPORTANCE The incidence of life-threatening multidrug-resistant Candida auris infections is rapidly growing, causing substantial economic costs due to outbreaks in hospital wards. Primary and secondary immunodeficiencies in susceptible individuals, such as those with leukemia, solid organ transplants, diabetes, and ongoing chemotherapy, often correlate with decreased plasma gelsolin concentration (hypogelsolinemia) and impairment of innate immune responses due to severe leukopenia. Immunocompromised patients are predisposed to superficial and invasive fungal infections. Morbidity caused by C. auris among immunocompromised patients can be as great as 60%. In the era of ever-growing fungal resistance in an aging society, it is critical to seek novel immunotherapies that may help combat these infections. The results reported here suggest the possibility of using pGSN as an immunomodulator of the immune response by neutrophils during C. auris infection.

Exploration of oxidized phosphocholine profile in non-small-cell lung cancer.

Introduction: Lung cancer is one of the most frequently studied types of cancer and represents the most common and lethal neoplasm. Our previous research on non-small cell lung cancer (NSCLC) has revealed deep lipid profile reprogramming and redox status disruption in cancer patients. Lung cell membranes are rich in phospholipids that are susceptible to oxidation, leading to the formation of bioactive oxidized phosphatidylcholines (oxPCs). Persistent and elevated levels of oxPCs have been shown to induce chronic inflammation, leading to detrimental effects. However, recent reports suggest that certain oxPCs possess anti-inflammatory, pro-survival, and endothelial barrier-protective properties. Thus, we aimed to measure the levels of oxPCs in NSCLC patients and investigate their potential role in lung cancer. Methods: To explore the oxPCs profiles in lung cancer, we performed in-depth, multi-level metabolomic analyses of nearly 350 plasma and lung tissue samples from 200 patients with NSCLC, including adenocarcinoma (ADC) and squamous cell carcinoma (SCC), the two most prevalent NSCLC subtypes and COPD patients as a control group. First, we performed oxPC profiling of plasma samples. Second, we analyzed tumor and non-cancerous lung tissues collected during the surgical removal of NSCLC tumors. Because of tumor tissue heterogeneity, subsequent analyses covered the surrounding healthy tissue and peripheral and central tumors. To assess whether the observed phenotypic changes in the patients were associated with measured oxPC levels, metabolomics data were augmented with data from medical records. Results: We observed a predominance of long-chain oxPCs in plasma samples and of short-chain oxPCs in tissue samples from patients with NSCLC. The highest concentration of oxPCs was observed in the central tumor region. ADC patients showed higher levels of oxPCs compared to the control group, than patients with SCC. Conclusion: The detrimental effects associated with the accumulation of short-chain oxPCs suggest that these molecules may have greater therapeutic utility than diagnostic value, especially given that elevated oxPC levels are a hallmark of multiple types of cancer.

Assessment of Pulmonary Function Tests in COVID-19 Convalescents Six Months after Infection.

Background: The aim of the study was to investigate the impact of COVID-19 on the pulmonary function tests (PFT) in COVID-19 convalescents six months after recovery. Additionally, the research question was whether PFT should be performed routinely in post-COVID-19 patients. Methods: A total of 39 patients with a history of COVID-19 6 months prior to the study were included in the study (Group I). Individuals were hospitalized or treated in the outpatients department. The control group (Group II) consisted of 39 healthy patients without a COVID-19 history. Each subject completed a questionnaire interview and underwent laboratory and pulmonary function examinations. Results: Six months after COVID-19 recovery, patients mainly complained about cough (46%, n = 18), shortness of breath (23%, n = 9), weakness (13%, n = 5), and memory/concentration disorders (8%, n = 3). In the group of patients complaining of persistent cough present 6 months after COVID-19, the following PFT parameters were decreased: FEV1, FVC, FRC, TLC, and DLCO (p < 0.05) in comparison with patients without this symptom. Conclusions: Persistent shortness of breath is not necessarily associated with pulmonary function impairment in patients 6 months after SARS-CoV-2 infection, and hence it requires appropriate differential diagnosis. Patients with a cough persisting 6 months after the acute phase of COVID-19 may benefit from PFT.