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Purpose: Interstitial lung disease (ILD) damages the lungs and can be caused by environmental exposures and collagen-vascular diseases. The systemic immune-inflammation index (SII) is investigated to diagnose and manage ILDs in different etiological diseases. The study aims to examine the usefulness of SII in diagnosing specific ILDs like Sjogren's syndrome (SjS)-ILD, interstitial pneumonia with autoimmune features (IPAF), and idiopathic pulmonary fibrosis (IPF)., Materials and Methods: In this cross-sectional study, we included 109 patients with IPAF, IPF, and SjS-ILD. Demographic characteristics, symptoms, lung patterns, autoantibodies, and SII were assessed. Morphologic, serologic, and clinical factors determined the classification of IPAF. Student's t-test, Mann-Whitney U test, Pearson-Spearman's method, and receiver operating characteristic (ROC) curves were used to analyze data., Results: Male patients were more common in IPF and IPAF, while SjS-ILD had mostly female patients. Raynaud's phenomenon and dry mouth/eyes were more common in SjS-ILD compared to IPF and IPAF. The groups had significant differences in patterns, antinuclear antibody positivity, and SII levels. SII levels differed significantly between IPAF, SjS-ILD, and IPF patients, and were correlated with CRP in IPAF and SjS-ILD. The cut-off value of the SII between IPAF and IPF in patients with ILD was 576.1 with 76.0% sensitivity and 76.0% specificity., Conclusions: Evaluation of SII provides valuable information for understanding and identifying different disease groups with ILDs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Cervical cancer poses a significant global health challenge, particularly impacting women in economically developing nations. This disparity stems from a combination of factors, including inadequate screening infrastructure and resource limitations. However, the foremost contributor is the widespread lack of awareness and limited accessibility to Human Papillomavirus (HPV) vaccination, which is a key preventative measure against cervical cancer development. Despite advancements in cervical cancer prevention, treatment resistance remains a major hurdle in achieving improved patient outcomes. Cellular senescence, specifically the senescence-associated secretory phenotype (SASP) and its bidirectional relationship with the immune system, has been implicated in resistance to conventional cervical cancer chemotherapy treatments. The exact mechanisms by which this state of growth arrest and the associated changes in immune regulation contribute to cervical cancer progression and the associated drug resistance are not entirely understood. This underscores the necessity for innovative strategies to address the prevalence of treatment-resistant cervical cancer, with one promising avenue being the utilisation of senolytics. Senolytics are agents that have promising efficacy in clearing senescent cells from tumour tissues, however neither the utilisation of senolytics for addressing senescence-induced treatment resistance nor the potential integration of immunotherapy as senolytic agents in cervical cancer treatment has been explored to date. This review provides a concise overview of the mechanisms underlying senescence induction and the pivotal role of the immune system in this process. Additionally, it explores various senolytic approaches that hold significant potential for advancing cervical cancer research., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Medical University of Bialystok. Published by Elsevier B.V. All rights reserved.)

Purpose: Recurrence is the main cause of hepatocellular carcinoma (HCC) related deaths. Underlying recurrence biology can be better understood by comparative analysis of the complete set of transcripts between recurrent and non-recurrent HCC. In this study, transcriptomic data (GSE56545) from 21 male patients diagnosed with either recurrent or non-recurrent HCC were reanalyzed to identify deregulated pathways, somatic mutations, fusion transcripts, alternative splicing events, and the immune context in recurrent HCC., Materials and Methods: DESeq2 was used for differential expression analysis, Mutect2 for somatic mutation analysis, Arriba and STAR-Fusion for fusion transcript analysis, and rMATs for alternative splicing analysis., Results: The results revealed that MYC targets gene sets (Hallmark_MYC_targets_V1 and Hallmark_MYC_targets_V2) were significantly enriched in recurrent HCC. Among the MYC targets, CBX3, NOP56, CDK4, NPM1, MCM5, MCM4 and PA2G4 upregulation was significantly associated with poor survival. Somatic mutation analysis demonstrated that the numbers of high confidence deleterious mutations were significantly increased in recurrent HCC. Alternative splicing-mediated production of non-functional DDB2 and oncogenic BRCA1 D11q were discovered in recurrent HCC. Finally, CD8 + T-cells were significantly decreased in recurrent HCC., Conclusions: These results indicated that the enrichment of MYC targets gene sets is one of the most critical factors that leads to the development of recurrent HCC. In addition, elevated deleterious mutation numbers and alternative spliced DDB2 and BRCA1 isoforms have been identified as prominent contributors to increasing genomic instability in male patients with recurrent HCC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Medical University of Bialystok. Published by Elsevier B.V. All rights reserved.)

Purpose: Breast cancer (BC) is the most common cancer diagnosed in the world and it is also the main leading cause of cancer deaths in women. Change in epigenetic mechanisms promotes BC initiation and progression. Histone deacetylase 8 (HDAC8) was found to act as a potential oncogene in different malignancies. For better understanding of the HDAC8 function in BC development, we investigated the effect of HDAC8 deletion on the expression of genes involved in signaling pathways., Materials and Methods: In this study, CRISPR technology was used to knockout the HDAC8 gene in MDA-MB-468, MDA-MB-231 and MCF-7 ​cell lines. For this purpose, two gRNAs were designed and cloned into the PX459 vector. The gRNA-containing vectors were transfected into the BC cell lines and then the effect of this deletion on the expression of genes involved in signaling pathway was determined using quantitative real-time PCR (qRT-PCR)., Results: Analysis of qRT-PCR results showed a reduction in the expression of studied genes in BC cell lines after deletion of the HDAC8 gene compared to untreated controls. Although this decline was not significant for FGF2 and FGFR1 genes, however the mTOR, IGF1R, INSR, VEGFA and VEGFR2 genes showed statistically significant reduction in the studied BC cell lines. In addition, the down-regulation of PDGFC and PDGFRA genes were only significant in the TNBC cell lines., Conclusion: Overall, our study showed that HDAC8 can exert its oncogenic effects by altering the expression level of molecules involved in some signaling pathways, and inhibiting HDAC8 can revert these effects., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Medical University of Bialystok. Published by Elsevier B.V. All rights reserved.)

Purpose: Recently, placenta-derived mesenchymal stem cells (PMSCs) have garnered considerable attention in tissue repair and regeneration. The present study was conducted to evaluate the effect of PMSCs on artificial dermal scaffold (ADS) angiogenesis and their combination therapy on wound closure., Material and Methods: Herein, the growth and survival of PMSCs in ADS were explored. CCK8, scratch wound, and tubule formation assays were employed to investigate the effects of ADS conditioned medium (CM) and ADS-PMSCs CM on human umbilical vein endothelial cells (HUVECs). The effect of ADS-PMSCs on full-thickness skin defects healing was evaluated based on a rat model. Wound healing progresses was meticulously investigated through hematoxylin and eosin (HE), Masson's trichrome, and immunohistochemical staining analyses., Results: In vitro cell culture results demonstrated the proliferation of PMSCs in ADS. The ADS-PMSCs CM notably stimulated the proliferation, migration, and tube formation of HUVECs compared to the ADS CM group. In the rat full-thickness skin defect model, the ADS-PMSCs treatment significantly accelerated the vascularization area of ADS after 2 weeks. Besides, HE and Masson's trichrome staining results indicated that ADS-PMSCs treatment significantly enhanced fibroblast proliferation and collagen fiber 2 weeks after surgical procedure. Compared to the ADS group, collagen fiber arrangement was thicker in the ADS-PMSCs group. Immunohistochemical staining reinforced this finding, illustrating a substantial increase in CD31 expression within the ADS-PMSCs group., Conclusions: The results suggest that the combination of ADS with PMSCs accelerates ADS vascularization by fostering granulation tissue development and boosting the formation of new blood vessels., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Medical University of Bialystok. Published by Elsevier B.V. All rights reserved.)

Purpose: Spontaneous bacterial peritonitis (SBP) is a bacterial infection of ascitic fluid that develops naturally, without being triggered by any surgical conditions or procedures, and is a common complication of cirrhosis. With a potential mortality rate of 40 ​%, accurate diagnosis and prompt initiation of appropriate antibiotic therapy are crucial for optimizing patient outcomes and preventing life-threatening complications. This study aimed to expand the use of computational models to improve the diagnostic accuracy of SBP in cirrhotic patients by incorporating a broader range of data, including clinical variables and laboratory values., Patients and Methods: We employed 5 machine learning classification methods - Decision Tree, Support Vector Machine, Naive Bayes, K-Nearest Neighbor, and Random Forest, utilizing a variety of demographic, clinical, and laboratory features and biomarkers., Results: Ascitic fluid markers, including white blood cell (WBC) count, lactate dehydrogenase (LDH), total protein, and polymorphonuclear cells (PMN), significantly differentiated between SBP and non-SBP patients. The Random Forest model demonstrated the highest overall accuracy at 86 ​%, while the Naive Bayes model achieved the highest sensitivity at 72 ​%. Utilizing 10 key features instead of the full feature set improved model performance, notably enhancing specificity and accuracy., Conclusion: Our analysis highlights the potential of machine learning to enhance the accuracy of SBP diagnosis in cirrhotic patients. Integrating these models into clinical workflows could substantially improve patient outcomes. To achieve this, ongoing multidisciplinary research is crucial. Ensuring model interpretability, continuous monitoring, and rigorous validation will be essential for the successful implementation of real-time clinical decision support systems., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Medical University of Bialystok. Published by Elsevier B.V. All rights reserved.)

Purpose: Co-administration of microRNAs and chemotherapy drugs effectively treats several cancers. The current study sought to investigate the function of matrix metalloproteinase 16 (MMP16) and miR-193a-5p in the pathogenesis of gastric cancer (GC)., Materials/methods: Sixty-five surgical patients, 15 receiving 5-fluorouracil (5-FU), provided GC and adjacent non-cancerous tissue. Following that, qPCR was used to assess the expression levels of MMP16 and miR-193a-5p in GC cells. The impact of miR-193a-5p and 5-FU administration on MMP16 mRNA expression was evaluated using qRT-PCR and Western blotting. MTT and Scratch tests were also conducted to assess their effects on cell viability and migration. Moreover, a rescue experiment using an MTT assay was performed. Using flow cytometry, the apoptotic rate was calculated. Finally, it was evaluated how MMP16 and miR-193a-5p related to the clinicopathological characteristics of the patients., Results: The current study found that while MMP16 expression increased in GC patients (P ​< ​0.0001), miR-193a-5p expression significantly decreased (P ​< ​0.001). MMP16 down-regulation was another effect of miR-193a-5p replacement, particularly when 5-FU was added (P ​< ​0.01). In addition, this study found that miR-193a-5p, by concentrating on MMP16, decreased the migration of GC cells brought on by MMP16. In GC cell lines, miR-193 and 5-FU induce apoptosis, with the 5-FU being more pronounced when combined with mir-193, according to flow cytometry results. A strong correlation was also found between clinicopathological traits associated with MMP16 and miR-193a-5p., Conclusions: These findings suggest that miR-193a-5p, in conjunction with 5-FU, down-regulates MMP16 in GC, where it suppresses tumor growth., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: The leucine-rich repeat-containing (LRRC) superfamily members are known for their significant roles in tumorigenesis and cellular proliferation. However, the specific regulatory role of LRRC45 in lung cancer remains unexplored. This study investigated the impact and underlying mechanisms of LRRC45 on the proliferative, migratory, and invasive capacities of lung adenocarcinoma (LUAD) cells, potentially identifying new targets for therapeutic intervention., Material and Methods: The importance of LRRC45 in lung cancer was analyzed using the online databases of UCSC Xena, TCGA, TISIDB, and UALCAN, whereas to detect target gene expression, we used the qRT-PCR, Western blot, and immunofluorescence confocal. The cell growth was monitored by colony formation assay and migration was examined by cell migration assay. Finally, a xenograft mouse tumor model using A549 ​cells was used to explore the in vivo effect of LRRC45 in lung cancer., Results: Inhibition of LRRC45 expression led to a notable decrease in proliferation, migration, and invasion of A549 and H1299 ​cells. LRRC45 silencing significantly reduced the tumor volume and improved the mice's survival. Additionally, inhibition of LRRC45 expression dramatically suppressed c-MYC, Slug, MMP2, and MMP9 expression. Overexpression of c-MYC and/or Slug in the LRRC45-deficient cells can partially or totally restore the LRRC45 deficiency-suppressed growth. Moreover, the overexpression of MMP2 and/or MMP9 could partially or totally restore LRRC45 deficiency-reduced cell metastasis., Conclusions: LRRC45 could promote the proliferative, migrative, and invasive capacities of lung cancer cells by increasing c-MYC, Slug, MMP2, and MMP9 expression, indicating the therapeutic implications and potential significance of these pathways in lung cancer., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Medical University of Bialystok. Published by Elsevier B.V. All rights reserved.)

Purpose: Vascular smooth muscle cell (VSMC) phenotype switch and dysfunctions have been reported to participate in aortic dissection (AD) progression. This study was aimed to investigate the role of angiopoietin-like 4 (ANGPTL4) in regulating VSMCs phenotype switch., Materials and Methods: Key genes were analyzed in AD using public datasets, and it was found that the central differential gene ANGPTL4 was up-regulated in AD. The KEGG signaling pathway annotation was performed to validate the associated pathways, and the expression of ANGPTL4 was verified using multiple datasets and clinical samples. Furthermore, the specific functions of ANGPTL4 on platelet-derived growth factor-BB (PDGF-BB)-treated human aortic smooth muscle cell (HASMC) phenotypes were investigated. The dynamic effects of ANGPTL4 and core signaling antagonists on HASMC phenotypes were examined., Results: Hub gene ANGPTL4 was significantly up-regulated in AD. ANGPTL4 was linked to the PI3K/Akt signaling, angiogenesis, and neovascularization and remodeling. ANGPTL4 overexpression further enhanced PDGF-BB effects on HASMC phenotypes, including promoted cell viability and migration, decreased contractile VSMC markers α-SMA and SM22α, elevated ECM degradation markers MMP-2 and MMP-9, and promoted phosphorylation of PI3K and Akt. ANGPTL4 knockdown partially abolished PDGF-BB-induced contractile/synthetic VSMCs imbalance and HASMC dysfunctions. Furthermore, in ANGPTL4-overexpressing HASMCs pre-treated with PDGF-BB, the PI3K/Akt signaling inhibitor LY294002 also partially eliminated the effects caused by the PDGF-BB treatment and ANGPTL4 overexpression., Conclusions: ANGPTL4 is significantly up-regulated in AD. ANGPTL4 overexpression further enhanced PDGF-BB effects on HASMC phenotype switch and dysfunctions, which might be involved in the PI3K/Akt signaling., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Medical University of Bialystok. Published by Elsevier B.V. All rights reserved.)

Purpose: Many types of cancer have infectious origins. Gastric cancer patients can demonstrate high seroprevalence of Helicobacter pylori (H. pylori). The aim of the present study was to assess the expression of SMOX gene in the group of Polish patients with gastric cancer. SMOX is believed to promote H. pylori-induced carcinogenesis via inflammation, DNA damage and activation of β-catenin signaling. We also assessed the mRNA expression of selected pro-inflammatory cytokines, i.e. IL-2, IFN-γ, TNF-α, and antimicrobial peptide, cathelicidin., Materials/methods: The study material consisted of gastric tissue samples collected during total gastrectomy from three different places in stomach: from primary tumor, 3 ​cm away from the primary lesion, and from the wall opposite to the primary tumor. After RNA isolation, qPCR reactions were performed for the relevant genes., Results: The obtained results confirmed an increased level of SMOX expression in gastric cancer patients with the history of H. pylori infection. And, as far as we know, this is the first study on SMOX gene expression conducted on tissue taken from a patient, not on a cell line. The levels of pro-inflammatory cytokines, i.e. IL-2, IFN-γ, TNF-α, were also increased, thus indicating their contribution to the specific inflammatory microenvironment of the tumor. Interestingly, the levels of CAMP, encoding antimicrobial peptide, were reduced in all tissue types., Conclusions: The findings confirm that SMOX plays a role in gastric carcinogenesis. However, further research is needed on the role of inflammatory and other factors involved in this process to identify targets for cancer immunotherapy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: The aim of this study was to investigate the effect of liquid platelet-rich fibrin (PRF) during tonsillectomy on postoperative results., Patients and Methods: This study included 41 patients who underwent tonsillectomy between April 2022 and January 2023. Liquid-PRF at a dose of 1 ​cc was injected to three different points of one of the tonsil fossae, selected at random intraoperatively. The same amount of physiological saline was injected to the symmetrical points on the opposite tonsil fossa using the same size injector. Pain, wound healing, and bleeding were evaluated on postoperative days 1, 7, and 14. The data of both sides were compared statistically as the study and control sides., Results: The pain scores were the highest for both sides on postoperative day 1, and gradually decreased in the following days, with no significant difference determined between the sides (p ​> ​0.05). Wound healing rates in the 1st week and 2 ​nd ​week were similar for both sides. Although there were more patients who have 100 ​% epithelization in the PRF group on the postoperative day 14, the difference between the groups was not statistically significant (p ​> ​0.05)., Conclusions: The injection of PRF following tonsillectomy had no significant effect on postoperative pain, wound healing, or bleeding., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Medical University of Bialystok. Published by Elsevier B.V. All rights reserved.)

Purpose: Inferior vena cava (IVC) involvement by renal cell carcinoma (RCC) is associated with a higher disease stage and is considered a risk factor for poor prognosis. This study aimed to investigate the role of the apparent diffusion coefficient (ADC) of MRI 3D texture analysis in the differentiation of solid and friable tumour thrombus in patients with RCC., Materials and Methods: The study involved 27 patients with RCC with tumour thrombus in the renal vein or IVC, surgically treated with nephrectomy and thrombectomy and in whom preoperatively abdominal MRI including the DWI sequence was conducted. For 3D texture analysis, the ADC map was used, and the first-order radiomic features were calculated from the whole volume of the thrombus. All tumour thrombi were histologically classified as solid or friable., Results: The solid and friable thrombus was detected in 51.9 ​% and 48.1 ​% of patients, respectively. No differences in mean values of range, 90th percentile, interquartile range, kurtosis, uniformity and variance were found between groups. Equal sensitivity and specificity (93 ​% and 69 ​%, respectively) of ADC mean, median and entropy in differentiation between solid and friable tumour thrombus, with the highest AUC for entropy (0.808), were observed. Applying the skewness threshold value of 0.09 allowed us to achieve a sensitivity of 86 ​% and a specificity of 92 ​%., Conclusions: In patients with RCC and tumour thrombus in the renal vein or IVC, the 3D texture analysis based on ADC-map allows for precise differentiation of a solid from a friable thrombus., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Medical University of Bialystok. Published by Elsevier B.V. All rights reserved.)

Purpose: Hematopoietic stem cell (HSC) transplant is one of the curative methods for some patients with hematological malignancies. Granulocyte colony-stimulating factor (G-CSF) is the most common drug used to mobilize CD34 + cells, generally found in small numbers. Recent evidence showed that exercise causes transient mobilization in HSC. However, the type and intensity of exercise have not been fully revealed. We aimed to detect a significant increase in stem cell levels following 60 ​min of running at a personalized running pace., Materials/methods: Eighteen runners, 48.2 ​± ​1.9 years with peak oxygen consumption of 46.2 ​± ​1.4 ​ml/kg/min, were enrolled in the study. The cardiopulmonary exercise test was performed to determine the individual running pace, and the participants ran 60-min on a treadmill at an intensity close to their ventilatory threshold (VT). The blood sampling for HSC count was performed before, immediately after, at the 1st, 4th and 24th hour after the 60-min running., Results: The CD34 + HSCs were 13.9 ​± ​2.3 ​cells/μl before and significantly increased immediately after to 19.5 ​± ​3.6 ​cells/μl (p ​< ​0.05). The consecutive HSC counts were 15.3 ​± ​2.2, 19.5 ​± ​4.8 and 15.1 ​± ​3.4 ​cells/μl at the 1st, 4th, and 24th hour, respectively., Conclusion: The individual data showed that some runners had higher HSC levels than the transplantation limit before and after the 60-min running trail, which was maintained for 24 ​h. Pre-running high CD34 + HSCs may reflect an adaptive response to regular exercise, with a 60-min run near the VT further elevating HSCs. Individualized exercise may be a valuable tool to mobilize the CD34 + HSCs in peripheral blood for donors., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Medical University of Bialystok. Published by Elsevier B.V. All rights reserved.)

Metabolic dysfunction-associated steatotic liver disease (MASLD) has been proposed as a new name for the previous non-alcoholic fatty liver disease (NAFLD). There are some differences between MASLD and NAFLD, e.g., diagnostic criteria. MASLD is a hepatic steatosis without harmful alcohol consumption and is caused by metabolic factors. The prevalence of MASLD varies amongst different populations. The change in lifestyle plays a fundamental role in MASLD management, while there is no registered pharmacotherapy in this indication. Sodium-glucose co-transporter 2 inhibitors (SGLT2i) have been suggested to have a beneficial effect on hepatic steatosis, hence, they have been widely investigated as potential therapeutics in MASLD. In this review, we aimed to thoroughly summarize current evidence from original research about the effects of SGLT2i use on MASLD. Almost all discussed studies advocate using SGLT2i in MASLD because of their beneficial effects. It includes the loss of body weight, which is beneficial per se, and the improvement in hepatic parameters. Most importantly, steatosis reduction has been observed in patients using SGLT2i. We highly recommend further research in this field, which we believe will eventually lead to a new indication for SGLT2i, i.e., MASLD., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: Patients bearing estrogen receptor (ER)α-negative breast cancer tumors confront poor prognosis and are typically unresponsive to hormone therapy. Previous studies have shown that calcitriol, the active vitamin D metabolite, can induce ERα expression in ERα-negative cells. EB1089, a calcitriol analog with reduced calcemic effects, exhibits greater potency than calcitriol in inhibiting cancer cell growth. However, the impact of EB1089 on ERα expression in triple-negative breast cancer (TNBC) cells remains unexplored. This study aims to investigate whether EB1089 could induce functional ERα expression in TNBC cell lines, potentially enabling the antiproliferative effects of antiestrogens., Materials and Methods: TNBC cell lines HCC1806 and HCC1937 were treated with EB1089, and ERα expression was analyzed using real-time PCR and Western blots. The transcriptional activity of induced ERα was evaluated through a luciferase reporter assay. The antiproliferative effects of tamoxifen and fulvestrant antiestrogens were assessed using the sulforhodamine B assay in the EB1089-treated cells., Results: Our findings indicated that EB1089 significantly induced ERα mRNA and protein expression in TNBC cells. Moreover, EB1089-induced ERα exhibited transcriptional activity and effectively restored the inhibitory effects of antiestrogens, thereby suppressing cell proliferation in TNBC cells., Conclusion: EB1089 induced the expression of functional ERα in TNBC cells, restoring the antiproliferative effects of antiestrogens. These results highlight the potential of using EB1089 as a promising strategy for re-establishment of the antiproliferative effect of antiestrogens as a possible management for TNBC. This research lays the foundation for potential advancements in TNBC treatment, offering new avenues for targeted and effective interventions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Medical University of Bialystok. Published by Elsevier B.V. All rights reserved.)

Purpose: The goal of the study was to identify markers of organ function used in daily routines that could potentially aid in the overall evaluation of the cardiovascular system in patients with right-ventricle heart failure due to pulmonary arterial hypertension (PAH) and left-ventricle heart failure. We analyzed correlations between parameters from right heart catheterization (RHC), cardiopulmonary exercise test (CPET), and selected laboratory parameters of thyroid, liver, kidneys function and iron homeostasis., Patients and Methods: A retrospective analysis included 107 patients (mean age 57.6 ​± ​16.2; 34.6 ​% women), comprising 57 patients with PAH (mean age 54.0 ​± ​18.2; 49.1 ​% women) and 50 patients with heart failure with reduced ejection fraction (HFrEF) ​< ​40 ​% (mean age 61.6 ​± ​12.7; 18 ​% women). All patients underwent CPET. Each patient in the PAH group had RHC performed. Fifteen patients from the HFrEF group underwent RHC, which confirmed the suspicion of pulmonary hypertension (HFrEF-SPH)., Results: CPET and laboratory parameters' analysis showed strong correlations between ventilation/carbon dioxide production (VE/VCO 2 ) slope and NT-proBNP in HFrEF without secondary PH and HFrEF-SPH groups. In the PAH group, VE/VCO 2 slope correlated with liver and thyroid function but also with morphological parameters of red-cell system. Analysis of correlations between laboratory and hemodynamic parameters revealed significant correlations between pulmonary arterial pressure, pulmonary vascular resistance (PVR) and red-cell parameters, especially strong with fT4 in the PAH group., Conclusions: In HFrEF-SPH patients, laboratory parameters strongly correlated with pulmonary pressures and pulmonary capillary wedge pressure (PCWP)., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Purpose: Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease characterized by a range of symptoms, including sleep disturbances. The present study aimed to investigate the prevalence of sleep disorders and the associations between sleep disorders and clinical outcomes in PBC., Patients and Methods: We enrolled 177 patients with PBC and 165 healthy controls (age- and sex-matched). Sleep quality was assessed by the Pittsburgh Sleep Quality Index (PSQI). Demographic and clinical data were collected from comprehensive clinical records to investigate whether sleep disorder was correlated with disease severity, therapeutic response and liver cirrhosis., Results: The prevalence of sleep disorders in patients with PBC (50.8 ​%) was significantly higher than healthy controls (18.2 ​%). Patients with sleep disorders presented with higher levels of laboratory parameters including globulin (GLO), aspartate aminotransferase (AST), alkaline phosphatase (ALP), glutamyl transpeptidase (GGT), total bilirubin (TBIL), direct bilirubin (DBIL) and immunoglobulin M (IgM), as well as higher ratio of poor therapeutic response and liver cirrhosis (p ​< ​0.05). There was a positive correlation between global PSQI score and AST, ALP, GGT, TBIL, DBIL and IgM in patients with PBC. Patients with poor therapeutic response and liver cirrhosis in PBC had a higher proportion of sleep disorders and more chaotic sleep patterns, whereas a stronger correlation between sleep quality and laboratory parameters was found in patients with liver cirrhosis., Conclusions: Sleep disorders were prevalent and manifested as adverse effects in PBC. Assessment of sleep quality and intervention were essential to the overall clinical management of patients with PBC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: Inflammation plays a crucial role in the development of atherosclerotic plaques. Pentraxin 3 (PTX3) is produced at the site of inflammation and has been identified as a specific marker of atherosclerosis, vascular inflammation, and progression of the coronary artery disease (CAD). The aim of the study was to establish if PTX3 has potential relations with classical markers of cardiovascular risk, and if PTX3 may act as an independent risk factor of CAD occurrence and advancement., Materials and Methods: The study included 98 patients with stable CAD confirmed in coronary angiography (CAD group) (median age 65 interquartile range [IQR] 61-72 years; 72 ​% men). The control group consisted of 40 patients without CAD., Results: The CAD group had significantly higher PTX3 concentration compared to the control group. There was a correlation with age, male gender, lipid profile and intima-media thickness. There was no correlation between PTX3 concentration and the number of coronary vessels with significant atherosclerotic lesions and the advancement of atherosclerotic lesions on the Gensini scoring scale. The cut-off point was determined for 0.89 ​ng/ml for the exclusion of angiographically significant atherosclerotic lesions., Conclusions: Patients with CAD have significantly higher concentration of PTX3. There was no correlation between PTX3 and the advancement of angiographically significant atherosclerotic lesions in coronary arteries. Low PTX3 concentration may serve as an indicator for the absence of atherosclerosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Purpose: Breast cancer is a complex disease with several molecular subtypes that respond differently to therapy. This paper describes liposomes loaded with gold nanoparticles as a targeted drug delivery method in the rapidly developing precision breast cancer treatment area. The aim was to investigate the cytotoxicity level and cellular uptake using several breast cancer cell lines and a normal breast cell line., Materials and Methods: We synthesized gold nanoparticles incorporated in liposomes. Nanostructures were incubated with breast cancer cell lines of different subtypes. The analysis included MTT assay, flow cytometry and immunofluorescence., Results: Cell viability varied among different cancer cells. Moreover, the time- and concentration-dependent manner of viability change was observed. The internalization of liposomes with gold nanoparticles and nanoparticles alone determined different results depending on molecular breast cancer subtypes. The luminal B and triple-negative breast cancer cells demonstrated the highest resistance and sensitivity, respectively. The intensity of cells' interaction with the proposed nanostructures was observed in both cell lines. In this study, we compare the molecular subtypes of breast cancer and discuss how this novel method might improve the therapy success., Conclusions: Our research sheds light on the possibility of new individualized treatments for breast cancer patients, opening the path for better results and a more detailed cancer therapy strategy., Competing Interests: Declaration of competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Purpose: Nuclear receptor subfamily 2 group E member 1 (Nr2e1) has been regarded as an essential regulator in neural stem cells. However, its function is still not clear in hepatocytes. This study aimed to clarify the effects of Nr2e1-deficiency in hepatocytes in lipotoxic conditions., Materials/methods: Nr2e1-knockdown AML12 ​cells were generated by lentiviral vector transfection. The influences of Nr2e1-deficiency on hepatocyte survival were determined by cell cycle progression and cell apoptosis rate using flow cytometry. Real-time quantitative PCR and Western blot were used to examine the genes and protein expression related to apoptosis, lipid metabolism, and oxidative stress. Meanwhile, RNA sequencing was adopted in liver samples from Nr2e1-knockout (Nr2e1-KO) mice., Results: Nr2e1 expression was observed with a significant decrease in AML12 ​cells after palmitic acid-stimulation. Knockdown of Nr2e1 in AML12 ​cells resulted in increased sensitivity to lipotoxicity, evidenced by a partial G0/G1 cell-cycle arrest and higher rates of cell apoptosis. Moreover, Nr2e1-knockdown AML12 ​cells presented increased gene expressions relative to lipid synthesis but decreased levels of β-oxidation related genes. Lack of Nr2e1 augmented palmitate-induced oxidative stress in hepatocytes. In vivo, differential genes in Nr2e1-KO mice liver were enriched in pathways associated with liver regeneration and cell proliferation., Conclusions: This study indicated that hepatocytes lacking Nr2e1 were more susceptible to lipotoxic-mediated damage. Nr2e1 may serve as a potential target for the development of novel therapies for lipotoxicity-induced liver injury., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interests related with to the publication of this paper., (Copyright © 2024. Published by Elsevier B.V.)

Hypoxia in the tumor core negatively affects the outcome of patients with head and neck squamous cell carcinoma (HNSCC). Nevertheless, its role in predicting treatment response requires further exploration. Typically, reduced oxygen levels in the tumor core correlate with diminished efficacy of radiotherapy, chemotherapy, and immunotherapy, which are commonly used for HNSCC patients' treatment. Understanding the mechanistic underpinnings of these varied treatment responses in HNSCC is crucial for enhancing therapeutic outcomes and extending patients' overall survival (OS) rates. Standard monolayer cell culture conditions have major limitations in mimicking tumor physiological features and the complexity of the tumor microenvironment. Three-dimensional (3D) cell cultures enable the recreation of the in vivo tumor attributes, encompassing oxygen and nutrient gradients, cellular morphology, and intracellular connections. It is vital to use the 3D model in treatment response studies to mimic the tumor microenvironment, as evidenced by the decreased sensitivity of 3D structures to anticancer therapy. Accordingly, the aim of the study was to delineate the utility of the 3D models of hypoxic head and neck tumors in drug screening and treatment response studies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: Escherichia coli (E. coli) and Shigella species, being highly similar, present a challenge for differentiation using classical methods such as phenotyping, 16S rRNA sequencing, or protein profiling using matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS). The paper proposes a method for identifying E. coli, S. flexneri, S. sonnei, and S. boydii by augmenting the Bruker Biotyper database with reference spectra of lipid profiles obtained using MALDI MS in the positive mode., Materials/methods: Lipid extracts were made from cultured E. coli, S. flexneri, S. sonnei and S. boydii using the Bligh & Dyer protocol. MALDI MS spectra in positive ion mode were performed for the extracts. Reference spectra were created from 30 spectra for each bacterium and added to the Bruker Biotyper database., Results: Identification of bacteria based on lipid profiles in the Biotyper database gave correct results with scores above 2.49. Statistical analysis of the results by Partial Least Squares-Discriminant Analysis (PLS-DA) showed that it is possible to correctly differentiate the microorganisms studied using the lipidomic approach. A panel of six m/z values was proposed for which the value of the area under the ROC curve is 1, thus enabling the identification of E. coli and S. flexneri with 100 ​% accuracy., Conclusions: Identification of bacteria from lipid fingerprints obtained by the MALDI MS technique is possible and may become a useful tool in the future, especially for microorganisms that are difficult to distinguish by other methods., Competing Interests: Declaration of competing interest The author declares no conflict of interests., (Copyright © 2024 Medical University of Bialystok. Published by Elsevier B.V. All rights reserved.)

Purpose: Idiopathic pulmonary fibrosis (IPF), a chronic and progressively worsening condition characterized by interstitial lung inflammation and fibrosis of unknown etiology, has a grim prognosis. The treatment options for IPF are limited and new therapeutic strategies are urgently needed. Dietary restriction can improve various inflammatory diseases, but its therapeutic effect on bleomycin (BLM)-induced pulmonary fibrosis mouse model remains unclear. This study aims to investigate whether intermittent fasting (IF) can alleviate BLM-induced pulmonary inflammation and fibrosis., Methods: Pulmonary fibrosis mouse models were induced by BLM. The IF group underwent 24-h fasting cycles for one week prior and three weeks following BLM administration. Meanwhile, the ad libitum feeding group had unrestricted access to food throughout the experiment. The evaluation focused on lung pathology via histological staining, qPCR analysis of collagen markers, and immune cell profiling through flow cytometry., Results: IF group significantly reduced inflammation and fibrosis in lung tissues of BLM-induced mice compared to ad libitum feeding group. qPCR results showed IF remarkably decreased the mRNA expression of Col 1a and Col 3a in the lungs of BLM-induced mouse models. IF also reduced the numbers of regulatory T cells (Tregs), T helper 17 (Th17) cells, monocytes, and monocyte-derived alveolar macrophages (MoAMs) in the lung tissues., Conclusions: IF may improve BLM-induced pulmonary fibrosis by decreasing numbers of immune cells including Treg cells, Th17 ​cells, monocytes, and MoAMs in the lungs. This study offers experimental validation for dietary intervention as a viable treatment modality in IPF management., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Medical University of Bialystok. Published by Elsevier B.V. All rights reserved.)

Purpose: The excessive fructose intake including high-fructose corn syrup (HFCS) may be responsible for increase of obesity occurrence. This study was designed to find potential differences in duodenal fructose transporters on mRNA and protein levels between obese and normal weight children and adolescents., Materials/methods: We performed a cross-sectional study on a group of 106 hospitalized patients aged 12 to 18. Glucose transporter 2 (GLUT2) and glucose transporter 5 (GLUT5) mRNA as well as protein levels (ELISA and Western blot methods) were assessed in duodenal mucosa biopsies of the patients categorized as obese or normal weight. Additionally, the expression of the aforementioned transporters was analyzed in patients based on the presence of insulin resistance (IR) and metabolic syndrome (MS)., Results: In children with obesity, increased duodenal protein levels of GLUT5 (Relative protein GLUT5 expression/ACTB) (0.027 ​± ​0.009 vs. 0.011 ​± ​0.006, p ​< ​0.05) but not GLUT2 as compared with the normal weight group, were revealed. No significant differences in duodenal relative GLUT2 and GLUT5 genes expression between the studied groups were found. There was no relationship between the presence of IR or MS and intestinal mRNA GLUT2 and GLUT5 as well as GLUT2 protein expression., Conclusion: The upregulation of the duodenal GLUT5 may contribute to obesity occurrence in children and adolescents., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)