Prevalence of increased intra-abdominal pressure and its impact on renal function in acute decompensated heart failure: A prospective pilot study.

BACKGROUND: Intra-abdominal pressure (IAP) is a frequently overlooked aspect in clinical assessment that can have a significant impact on organ dysfunction in patients with acute decompensated heart failure (ADHF). AIMS: We aimed to investigate dynamics of IAP in patients with ADHF and its impact on diuretic response. METHODS: We conducted a prospective observational pilot study on a group consisting of 30 patients admitted for ADHF. In every individual IAP measurement, blood and urine samples were taken upon admission, on the second and third days of hospitalization. RESULTS: The study showed a high (63.3%) prevalence of intra-abdominal hypertension (IAH) defined as IAP ≥12 mm Hg upon admission, while only roughly 13% had signs of ascites. We observed poorer diuresis on the first day of hospitalization in the IAH group (P = 0.03). IAP was negatively correlated with urine output (P = 0.01) and positively correlated with urine osmolality (P = 0.03) on the first day of hospitalization. During follow-up, there was a significant decrease in IAP in patients with IAH upon admission who received standard decongestive therapy. CONCLUSIONS: The study shows a high prevalence of IAH in patients admitted for ADHF, even in individuals who do not present symptoms of abdominal congestion. Established correlation between IAP, reduced diuresis, and increased urine osmolality, despite achieving target natriuresis, contributes novel insights into the understanding of pathomechanisms underlying diuretic resistance in ADHF.

Insulin and Metformin Administration: Unravelling the Multifaceted Association with Mortality across Various Clinical Settings Considering Type 2 Diabetes Mellitus and COVID-19.

Due to the molecular mechanisms of action of antidiabetic drugs, they are considered to be effective in the treatment of both COVID-19 and the post-COVID-19 syndromes. The aim of this study was to determine the effect of administering insulin and metformin on the mortality of patients with type 2 diabetes (T2DM) with symptomatic COVID-19 with the use of logistic regression models. The association between death and insulin and metformin was weak and could not be included in the multivariate model. However, the interaction of both drugs with other factors, including remdesivir and low-molecular-weight heparin (metformin), age and hsCRP (insulin), modulated the odds of death. These interactions hint at multifaceted (anti-/pro-) associations of both insulin and metformin with the odds of death, depending on the patient's characteristics. In the multivariate model, RDW-SD, adjusted with low-molecular-weight heparin treatment, age, sex and K+, was associated with mortality among patients with COVID-19 and T2DM. With a 15% increase in RDW-SD, the risk of death increased by 87.7%. This preliminary study provides the foundations for developing further, more personalized models to assess the risk of death in T2DM patients, as well as for identifying patients at an increased risk of death due to COVID-19.

Macrophage Inflammatory Proteins (MIPs) Contribute to Malignant Potential of Colorectal Polyps and Modulate Likelihood of Cancerization Associated with Standard Risk Factors.

Better understanding of molecular changes leading to neoplastic transformation is prerequisite to optimize risk assessment and chemopreventive and surveillance strategies. Data on macrophage inflammatory proteins (MIPs) in colorectal carcinogenesis are scanty and their clinical relevance remains unknown. Therefore, transcript and protein expression of CCL3, CCL4, CXCL2, and CCL19 were determined in 173 and 62 patients, respectively, using RT-qPCR and immunohistochemistry with reference to polyps' characteristics. The likelihood of malignancy was modeled using probit regression. With the increasing malignancy potential of hyperplastic-tubular-tubulo-villous-villous polyps, the expression of CCL3, CCL4, and CCL19 in lesions decreased. CCL19 expression decreased also in normal mucosa while that of CXCL2 increased. Likewise, lesion CCL3 and lesion and normal mucosa CCL19 decreased and normal CXCL2 increased along the hyperplasia-low-high dysplasia grade. The bigger the lesion, the lower CCL3 and higher CXCL2 in normal mucosa. Singular polyps had higher CCL3, CCL4, and CCL19 levels in normal mucosa. CCL3, CCL4 and CXCL2 modulated the likelihood of malignancy associated with traditional risk factors. There was no correlation between the protein and mRNA expression of CCL3 and CCL19. In summary, the polyp-adjacent mucosa contributes to gaining potential for malignancy by polyps. MIPs may help in specifying cancerization probability estimated based on standard risk factors.

Application of metabolomics in diagnostics and differentiation of meningitis: A narrative review with a critical approach to the literature.

Due to its high mortality rate associated with various life-threatening sequelae, meningitis poses a vital problem in contemporary medicine. Numerous algorithms, many of which were derived with the aid of artificial intelligence, were brought up in a strive for perfection in predicting the status of sepsis-related survival or exacerbation. This review aims to provide key insights on the contextual utilization of metabolomics. The aim of this the metabolomic approach set of methods can be used to investigate both bacterial and host metabolite sets from both the host and its microbes in several types of specimens - even in one's breath, mainly with use of two methods - Mass Spectrometry (MS) and Nuclear Magnetic Resonance (NMR). Metabolomics, and has been used to elucidate the mechanisms underlying disease development and metabolic identification changes in a wide range of metabolite contents, leading to improved methods of diagnosis, treatment, and prognosis of meningitis. Mass spectrometry (MS) and Nuclear Magnetic Resonance (NMR) are the main analytical platforms used in metabolomics. Its high sensitivity accounts for the usefulness of metabolomics in studies into meningitis, its sequelae, and concomitant comorbidities. Metabolomics approaches are a double-edged sword, due to not only their flexibility, but also - high complexity, as even minor changes in the multi-step methods can have a massive impact on the results. Information on the differential diagnosis of meningitis act as a background in presenting the merits and drawbacks of the use of metabolomics in context of meningeal infections.

Sex-stratified patterns of emergency cardiovascular admissions prior and during the COVID-19 pandemic.

The COVID-19 pandemic has had a significant impact on global public health, with long-term consequences that are still largely unknown. This study aimed to assess the data regarding acute cardiovascular hospital admissions in five European centers before and during the pandemic. A multicenter, multinational observational registry was created, comparing admissions to the emergency departments during a 3-months period in 2020 (during the pandemic) with the corresponding period in 2019 (pre-pandemic). Data on patient demographics, COVID-19 test results, primary diagnosis, comorbidities, heart failure profile, medication use, and laboratory results were collected. A total of 8778 patients were included in the analysis, with 4447 patients in 2019 and 4331 patients in 2020. The results showed significant differences in the distribution of cardiovascular diseases between the two years. The frequency of pulmonary embolism (PE) increased in 2020 compared to 2019, while acute heart failure (AHF) and other cardiovascular diseases decreased. The odds of PE incidence among hospitalized patients in 2020 were 1.316-fold greater than in 2019. The incidence of AHF was 50.83% less likely to be observed in 2020, and the odds for other cardiovascular diseases increased by 17.42% between the 2 years. Regarding acute coronary syndrome (ACS), the distribution of its types differed between 2019 and 2020, with an increase in the odds of ST-segment elevation myocardial infarction (STEMI) in 2020. Stratification based on sex revealed further insights. Among men, the incidence of AHF decreased in 2020, while other cardiovascular diseases increased. In women, only the incidence of STEMI showed a significant increase. When analyzing the influence of SARS-CoV-2 infection, COVID-positive patients had a higher incidence of PE compared to COVID-negative patients. COVID-positive patients with ACS also exhibited symptoms of heart failure more frequently than COVID-negative patients. These findings provide valuable information on the impact of the COVID-19 pandemic on acute cardiovascular hospital admissions. The increased incidence of PE and changes in the distribution of other cardiovascular diseases highlight the importance of monitoring and managing cardiovascular health during and post pandemic period. The differences observed between sexes emphasize the need for further research to understand potential sex-specific effects of COVID-19 on cardiovascular outcomes.

Alterations in Serum Concentration of Soluble CD163 within Five Study Days from ICU Admission Are Associated with In-Hospital Mortality of Septic Patients-A Preliminary Study.

BACKGROUND: CD163, a cell membrane surface molecule specifically expressed by macrophages with an anti-inflammatory phenotype, participates in innate immunity. The purpose of the study was to evaluate the clinical utility of sCD163 in septic patients in comparison to other parameters associated with infections, mainly PCT, CRP and IL-18. METHODS: Serum samples were obtained from 40 septic patients on the ICU admission day, 3rd and 5th study days. The control group consisted of 30 healthy volunteers from whom the specimen was collected once. An enzyme-linked immunosorbent assay (ELISA) was used to determine the concentrations of sCD163 and IL-18. CRP and PCT records, among others, were provided by the hospital. RESULTS: Septic shock was associated with the highest concentrations of sCD163 and IL-18. Admission values of sCD163 significantly contributed to mortality prediction in septic patients. CONCLUSIONS: The concentration of sCD163 determined on the ICU admission day may potentially be utilized in estimation of the odds of death among septic patients.

Do Body Mass Index and Nutritional Risk Score 2002 Influence the In-Hospital Mortality of Patients Following Cardiac Arrest?

BACKGROUND: Contemporarily, cardiac arrest (CA) remains one of the leading causes of death. Poor nutritional status can increase the post-CA mortality risk. The aim of this study was to determine the relationship between body mass index (BMI) and Nutritional Risk Score 2002 (NRS 2002) results and in-hospital mortality in patients admitted to the intensive care unit (ICU) after in-hospital and out-of-hospital cardiac arrest. METHODS: A retrospective study and analysis of medical records of 161 patients admitted to the ICU of the University Clinical Hospital in Wroclaw (Wroclaw, Poland) was conducted. RESULTS: No significant differences in body mass index (BMI) and nutritional risk score (NRS 2002) values were observed between non-survivors and survivors. Non-survivors had significantly lower albumin concentration (p = 0.017) and total cholesterol (TC) (p = 0.015). In multivariate analysis BMI and NRS 2002 scores were not, per se, associated with the in-hospital mortality defined as the odds of death (Model 1: p: 0.700, 0.430; Model 2: p: 0.576, 0.599). Univariate analysis revealed significant associations between the hazard ratio (HR) and TG (p ≈ 0.017, HR: 0.23) and hsCRP (p ≈ 0.018, HR: 0.34). In multivariate analysis, mortality risk over time was influenced by higher scores in parameters such as BMI (HR = 0.164; p = 0.048) and hsCRP (HR = 1.006, p = 0.002). CONCLUSIONS: BMI and NRS 2002, on their own (unconditionally - in the whole study group) did not alter the odds of mortality in patients admitted to the intensive care unit (ICU) after in-hospital and out-of-hospital cardiac arrest. The risk of in-hospital mortality (expressed as hazard ratio - the risk over the time period of the study) increased with an increase in BMI but not with NRS 2002.

COVID-19 Related Myocarditis in Adults: A Systematic Review of Case Reports.

Despite the progress of its management, COVID-19 maintains an ominous condition which constitutes a threat, especially for the susceptible population. The cardiac injury occurs in approximately 30% of COVID-19 infections and is associated with a worse prognosis. The clinical presentation of cardiac involvement can be COVID-19-related myocarditis. Our review aims to summarise current evidence about that complication. The research was registered at PROSPERO (CRD42022338397). We performed a systematic analysis using five different databases, including i.a. MEDLINE. Further, the backward snowballing technique was applied to identify additional papers. Inclusion criteria were: full-text articles in English presenting cases of COVID-19-related myocarditis diagnosed by the ESC criteria and patients over 18 years old. The myocarditis had to occur after the COVID-19 infection, not vaccination. Initially, 1588 papers were screened from the database search, and 1037 papers were revealed in the backward snowballing process. Eventually, 59 articles were included. Data about patients' sex, age, ethnicity, COVID-19 confirmation technique and vaccination status, reported symptoms, physical condition, laboratory and radiological findings, applied treatment and patient outcome were investigated and summarised. COVID-19-related myocarditis is associated with the risk of sudden worsening of patients' clinical status, thus, knowledge about its clinical presentation is essential for healthcare workers.

Cornelian Cherry (Cornus mas L.) Extracts Exert Cytotoxicity in Two Selected Melanoma Cell Lines-A Factorial Analysis of Time-Dependent Alterations in Values Obtained with SRB and MTT Assays.

Despite the fact that phytochemicals of Cornaceae species have long been discussed as possible auxiliary agents in contemporary treatment, the insights on their properties remain relatively scarce. This study focuses on Cornus mas L. (Cornelian cherry), the extracts of which are reported to exert a pleiotropic effect shown in both in vivo and in vitro studies. This study aimed to explore the cytotoxic effect of extracts from fruits of red (Cornus mas L. 'Podolski') and yellow (Cornus mas L. 'Yantarnyi' and 'Flava') Cornelian cherries on two melanoma cell lines (A375 and MeWo). The extracts were characterized in the context of the concentration of bioactive compounds of antioxidative properties. Cytotoxicity was investigated with the use of the following two assays: SRB and MTT. An additional, alternative protocol for the SRB assay was used in this study so as to account for possible bias. Cytotoxicity was assessed as a difference in the whole time series of cell viability, instead of analyzing differences in raw values (often found in the literature). Both extracts from Cornus mas L. induced cytotoxicity in both A375 and MeWo cell lines, although the response of these cells was different. Moreover, based on this study, there is no evidence for claiming a different magnitude of cytotoxicity between these two extracts.

Monocyte Chemotactic Proteins (MCP) in Colorectal Adenomas Are Differently Expressed at the Transcriptional and Protein Levels: Implications for Colorectal Cancer Prevention.

The expression of monocyte chemotactic proteins (MCPs) in colorectal polyps and their suitability as targets for chemoprevention is unknown, although MCP expression and secretion can be modulated by non-steroidal inflammatory drugs. This study was designed to determine the expression patterns of MCP-1/CCL2, MCP-2/CCL8, and MCP-3/CCL7 at the protein (immunohistochemistry; n = 62) and transcriptional levels (RTqPCR; n = 173) in colorectal polyps with reference to the polyp malignancy potential. All chemokines were significantly upregulated in polyps at the protein level but downregulated at the transcriptional level by 1.4-(CCL2), 1.7-(CCL7), and 2.3-fold (CCL8). There was an inverse relation between the immunoreactivity toward chemokine proteins and the number of corresponding transcripts in polyps (CCL2 and CCL7) or in normal mucosa (CCL8). The downregulation of chemokine transcripts correlated with the presence of multiple polyps (CCL2 and CCL8), a larger polyp size (CCL2, CCL7, and CCL8), predominant villous growth patterns (CCL2, CCL7 and CCL8), and high-grade dysplasia (CCL2 and CCL8). In conclusion, MCP-1/CCL2, MCP-2/CCL8, and MCP-3/CCL7 chemokines are counter-regulated at the protein and transcriptional levels. Chemokine-directed chemopreventive strategies should therefore directly neutralize MCP proteins or target molecular pathways contributing to their enhanced translation or reduced degradation, rather than aiming at CCL2, CCL7 or CCL8 expression.

Modulation of Prostanoids Profile and Counter-Regulation of SDF-1α/CXCR4 and VIP/VPAC2 Expression by Sitagliptin in Non-Diabetic Rat Model of Hepatic Ischemia-Reperfusion Injury.

Molecular mechanisms underlying the beneficial effect of sitagliptin repurposed for hepatic ischemia-reperfusion injury (IRI) are poorly understood. We aimed to evaluate the impact of IRI and sitagliptin on the hepatic profile of eicosanoids (LC-MS/MS) and expression/concentration (RTqPCR/ELISA) of GLP-1/GLP-1R, SDF-1α/CXCR4 and VIP/VPAC1, VPAC2, and PAC1 in 36 rats. Animals were divided into four groups and subjected to ischemia (60 min) and reperfusion (24 h) with or without pretreatment with sitagliptin (5 mg/kg) (IR and SIR) or sham-operated with or without sitagliptin pretreatment (controls and sitagliptin). PGI2, PGE2, and 13,14-dihydro-PGE1 were significantly upregulated in IR but not SIR, while sitagliptin upregulated PGD2 and 15-deoxy-12,14-PGJ2. IR and sitagliptin non-significantly upregulated GLP-1 while Glp1r expression was borderline detectable. VIP concentration and Vpac2 expression were downregulated in IR but not SIR, while Vpac1 was significantly downregulated solely in SIR. IRI upregulated both CXCR4 expression and concentration, and sitagliptin pretreatment abrogated receptor overexpression and downregulated Sdf1. In conclusion, hepatic IRI is accompanied by an elevation in proinflammatory prostanoids and overexpression of CXCR4, combined with downregulation of VIP/VPAC2. Beneficial effects of sitagliptin during hepatic IRI might be mediated by drug-induced normalization of proinflammatory prostanoids and upregulation of PGD2 and by concomitant downregulation of SDF-1α/CXCR4 and reinstating VIP/VCAP2 signaling.

An analysis of urine and serum amino acids in critically ill patients upon admission by means of targeted LC-MS/MS: a preliminary study.

Sepsis, defined as a dysregulated host response to infection, causes the interruption of homeostasis resulting in metabolic changes. An examination of patient metabolites, such as amino acids, during the early stage of sepsis may facilitate diagnosing and assessing the severity of the sepsis. The aim of this study was to compare patterns of urine and serum amino acids relative to sepsis, septic shock and survival. Urine and serum samples were obtained from healthy volunteers (n = 15) once or patients (n = 15) within 24 h of a diagnosis of sepsis or septic shock. Concentrations of 25 amino acids were measured in urine and serum samples with liquid chromatography-electrospray mass spectrometry. On admission in the whole cohort, AAA, ABA, mHis, APA, Gly-Pro and tPro concentrations were significantly lower in the serum than in the urine and Arg, Gly, His, hPro, Leu, Ile, Lys, Orn, Phe, Sarc, Thr, Tyr, Asn and Gln were significantly higher in the serum than in the urine. The urine Gly-Pro concentration was significantly higher in septic shock than in sepsis. The serum Cit concentration was significantly lower in septic shock than in sepsis. The urine ABA, mHis and Gly-Pro, and serum Arg, hPro and Orn concentrations were over two-fold higher in the septic group compared to the control group. Urine and serum amino acids measured in septic patients on admission to the ICU may shed light on a patient's metabolic condition during sepsis or septic shock.

Role of Advanced Glycation End-Products and Other Ligands for AGE Receptors in Thyroid Cancer Progression.

To date, thyroid cancers (TCs) remain a clinical challenge owing to their heterogeneous nature. The etiopathology of TCs is associated not only with genetic mutations or chromosomal rearrangements, but also non-genetic factors, such as oxidative-, nitrosative-, and carbonyl stress-related alterations in tumor environment. These factors, through leading to the activation of intracellular signaling pathways, induce tumor tissue proliferation. Interestingly, the incidence of TCs is often coexistent with various simultaneous mutations. Advanced glycation end-products (AGEs), their precursors and receptors (RAGEs), and other ligands for RAGEs are reported to have significant influence on carcinogenesis and TCs progression, inducing gene mutations, disturbances in histone methylation, and disorders in important carcinogenesis-related pathways, such as PI3K/AKT/NF-kB, p21/MEK/MPAK, or JAK/STAT, RAS/ERK/p53, which induce synthesis of interleukins, growth factors, and cytokines, thus influencing metastasis, angiogenesis, and cancer proliferation. Precursors of AGE (such as methylglyoxal (MG)) and selected ligands for RAGEs: AS1004, AS1008, and HMGB1 may, in the future, become potential targets for TCs treatment, as low MG concentration is associated with less aggressive anaplastic thyroid cancer, whereas the administration of anti-RAGE antibodies inhibits the progression of papillary thyroid cancer and anaplastic thyroid cancer. This review is aimed at collecting the information on the role of compounds, engaged in glycation process, in the pathogenesis of TCs. Moreover, the utility of these compounds in the diagnosis and treatment of TCs is thoroughly discussed. Understanding the mechanism of action of these compounds on TCs pathogenesis and progression may potentially be the grounds for the development of new treatment strategies, aiming at quality-of-life improvements.

Altered L-Arginine Metabolic Pathways in Gastric Cancer: Potential Therapeutic Targets and Biomarkers.

There is a pressing need for molecular targets and biomarkers in gastric cancer (GC). We aimed at identifying aberrations in L-arginine metabolism with therapeutic and diagnostic potential. Systemic metabolites were quantified using mass spectrometry in 293 individuals and enzymes' gene expression was quantified in 29 paired tumor-normal samples using qPCR and referred to cancer pathology and molecular landscape. Patients with cancer or benign disorders had reduced systemic arginine, citrulline, and ornithine and elevated symmetric dimethylarginine and dimethylamine. Citrulline and ornithine depletion was accentuated in metastasizing cancers. Metabolite diagnostic panel had 91% accuracy in detecting cancer and 70% accuracy in differentiating cancer from benign disorders. Gastric tumors had upregulated NOS2 and downregulated ASL, PRMT2, ORNT1, and DDAH1 expression. NOS2 upregulation was less and ASL downregulation was more pronounced in metastatic cancers. Tumor ASL and PRMT2 expression was inversely related to local advancement. Enzyme up- or downregulation was greater or significant solely in cardia subtype. Metabolic reprogramming in GC includes aberrant L-arginine metabolism, reflecting GC subtype and pathology, and is manifested by altered interplay of its intermediates and enzymes. Exploiting L-arginine metabolic pathways for diagnostic and therapeutic purposes is warranted. Functional studies on ASL, PRMT2, and ORNT1 in GC are needed.

Sitagliptin Modulates Oxidative, Nitrative and Halogenative Stress and Inflammatory Response in Rat Model of Hepatic Ischemia-Reperfusion.

A possibility of repurposing sitagliptin, a well-established antidiabetic drug, for alleviating injury caused by ischemia-reperfusion (IR) is being researched. The aim of this study was to shed some light on the molecular background of the protective activity of sitagliptin during hepatic IR. The expression and/or concentration of inflammation and oxidative stress-involved factors have been determined in rat liver homogenates using quantitative RT-PCR and Luminex® xMAP® technology and markers of nitrative and halogenative stress were quantified using targeted metabolomics (LC-MS/MS). Animals (n = 36) divided into four groups were treated with sitagliptin (5 mg/kg) (S and SIR) or saline solution (C and IR), and the livers from IR and SIR were subjected to ischemia (60 min) and reperfusion (24 h). The midkine expression (by 2.2-fold) and the free 3-nitrotyrosine (by 2.5-fold) and IL-10 (by 2-fold) concentration were significantly higher and the Nox4 expression was lower (by 9.4-fold) in the IR than the C animals. As compared to IR, the SIR animals had a lower expression of interleukin-6 (by 4.2-fold) and midkine (by 2-fold), a lower concentration of 3-nitrotyrosine (by 2.5-fold) and a higher Nox4 (by 2.9-fold) and 3-bromotyrosine (by 1.4-fold). In conclusion, IR disturbs the oxidative, nitrative and halogenative balance and aggravates the inflammatory response in the liver, which can be attenuated by low doses of sitagliptin.

Klebsiella pneumoniae enolase-like membrane protein interacts with human plasminogen.

Many models assessing the risk of sepsis utilize the knowledge of the constituents of the plasminogen system, as it is proven that some species of bacteria can activate plasminogen, as a result of interactions with bacterial outer membrane proteins. However, much is yet to be discovered about this interaction since there is little information regarding some bacterial species. This study is aimed to check if Klebsiella pneumoniae, one of the major factors of nosocomial pneumonia and a factor for severe sepsis, has the ability to bind to human plasminogen. The strain used in this study, PCM 2713, acted as a typical representative of the species. With use of various methods, including: electron microscopy, 2-dimensional electrophoresis, immunoblotting and peptide fragmentation fingerprinting, it is shown that Klebsiella pneumoniae binds to human plasminogen, among others, due to plasminogen-bacterial enolase-like protein interaction, occurring on the outer membrane of the bacterium. Moreover, the study reveals, that other proteins, such as: phosphoglucomutase, and phosphoenolpyruvate carboxykinase act as putative plasminogen-binding factors. These information may virtually act as a foundation for future studies investigating: the: pathogenicity of Klebsiella pneumoniae and means for prevention from the outcomes of Klebsiella-derived sepsis.

Activity of CdTe Quantum-Dot-Tagged Superoxide Dismutase and Its Analysis in Capillary Electrophoresis.

Quantum dots (QDs) have a broad range of applications in cell biolabeling, cancer treatment, metastasis imaging, and therapeutic drug monitoring. Despite their wide use, relatively little is known about their influence on other molecules. Interactions between QDs and proteins can influence the properties of both nanoparticles and proteins. The effect of mercaptosuccinic acid-capped CdTe QDs on intercellular copper-zinc superoxide dismutase (SOD1)-one of the main enzymatic antioxidants-was investigated. Incubation of SOD1 with QDs caused an increase in SOD1 activity, unlike in the case of CdCl2, which inhibited SOD1. Moreover, this effect on SOD1 increased with the size and potential of QDs, although the effect became clearly visible in higher concentrations of QDs. The intensity of QD-SOD1 fluorescence, analyzed with the use of capillary electrophoresis with laser-induced fluorescence detection, was dependent on SOD1 concentration. In the case of green QDs, the fluorescence signal decreased with increasing SOD1 concentration. In contrast, the signal strength for Y-QD complexes was not dependent on SOD1 dilutions. The migration time of QDs and their complexes with SOD1 varied depending on the type of QD used. The migration time of G-QD complexes with SOD1 differed slightly. However, in the case of Y-QD complexes with SOD1, the differences in the migration time were not dependent on SOD concentration. This research shows that QDs interact with SOD1 and the influence of QDs on SOD activity is size-dependent. With this knowledge, one might be able to control the activation/inhibition of specific enzymes, such as SOD1.

Concentration/activity of superoxide dismutase isozymes and the pro-/antioxidative status, in context of type 2 diabetes and selected single nucleotide polymorphisms (genes: INS, SOD1, SOD2, SOD3) - Preliminary findings.

The alterations in concentration/activity of superoxide dismutase isozymes in the context of type 2 diabetes or obesity are well-described. Moreover, many hereditary factors, including single-nucleotide polymorphisms (SNPs) of genes for coding insulin, insulin receptors, or insulin receptor substrates (INS, INSR, IRS1, IRS2) or superoxide dismutase isozymes (SOD1, SOD2, SOD3), have been linked with the incidence of obesity and diabetes. However, the underlying changes in the plasma concentration/activity of superoxide dismutase isozymes and their potential connection with the said hereditary factors remain unexplored. Previously, we have observed that the plasma concentration/activity of superoxide dismutase isozymes differs in the context of obesity and/or rs2234694 (SOD1) and rs4880 (SOD2) and that the concentrations of SOD1, SOD2, SOD3 are correlated with each other. Intersexual variability of SOD1 concentration was detected regardless of obesity. In this study, the variability of concentration/activity of superoxide dismutase isozymes in plasma is considered in the context of type 2 diabetes and/or SNPs: rs2234694 (SOD1), rs5746105 (SOD2), rs4880 (SOD2), rs927450 (SOD2), rs8192287 (SOD3). Genotypic variability of SNP rs3842729 (INS), previously studied in the context of insulin-dependent diabetes, is investigated in terms of selected clinical parameters associated with type 2 diabetes. This study revealed higher SOD1 concentration in diabetic men compared to women, and extremely high SOD1 concentration, higher total superoxide dismutase, and copper-zinc superoxide dismutase activity, and lower superoxide dismutase and copper-zinc superoxide dismutase activity (when adjusted for the concentration of SODs) in the diabetic group regardless of sex. Multiple logistic regression, applied to explore possible links between the studied SNPs and other factors with the odds of type 2 diabetes or obesity, revealed that the genotypic variability of rs4880 (SOD2) could affect these odds, supporting the findings of several other studies.

Esophageal Squamous Cell Carcinoma Is Accompanied by Local and Systemic Changes in L-arginine/NO Pathway.

The L-arginine/NO pathway holds promise as a source of potential therapy target and biomarker; yet, its status and utility in esophageal squamous cell carcinoma (ESCC) is unclear. We aimed at quantifying pathway metabolites in sera from patients with ESCC (n = 61) and benign conditions (n = 62) using LC-QTOF-MS and enzyme expression in esophageal tumors and matched noncancerous samples (n = 40) using real-time PCR with reference to ESCC pathology and circulating immune/inflammatory mediators, quantified using Luminex xMAP technology. ESCC was associated with elevated systemic arginine and asymmetric dimethylarginine. Citrulline decreased and arginine bioavailability increased along with increasing ESCC advancement. Compared to adjacent tissue, tumors overexpressed ODC1, NOS2, PRMT1, and PRMT5 but had downregulated ARG1, ARG2, and DDAH1. Except for markedly higher NOS2 and lower ODC1 in tumors from M1 patients, the pathology-associated changes in enzyme expression were subtle and present also in noncancerous tissue. Both the local enzyme expression level and systemic metabolite concentration were related to circulating inflammatory and immune mediators, particularly those associated with eosinophils and those promoting viability and self-renewal of cancer stem cells. Metabolic reprogramming in ESCC manifests itself by the altered L-arginine/NO pathway. Upregulation of PRMTs in addition to NOS2 and ODC1 and the pathway link with stemness-promoting cytokines warrants further investigation.

L-Arginine/Nitric Oxide Pathway Is Altered in Colorectal Cancer and Can Be Modulated by Novel Derivatives from Oxicam Class of Non-Steroidal Anti-Inflammatory Drugs.

L-arginine/nitric oxide pathway metabolites are altered in colorectal cancer (CRC). We evaluated underlying changes in pathway enzymes in 55 paired tumor/tumor-adjacent samples and 20 normal mucosa using quantitative-PCR and assessed the impact of classic and novel oxicam analogues on enzyme expression and intracellular metabolite concentration (LC-MS/MS) in Caco-2, HCT116, and HT-29 cells. Compared to normal mucosa, ARG1, PRMT1, and PRMT5 were overexpressed in both tumor and tumor-adjacent tissue and DDAH2 solely in tumor-adjacent tissue. Tumor-adjacent tissue had higher expression of ARG1, DDAH1, and DDAH2 and lower NOS2 than patients-matched tumors. The ARG1 expression in tumors increased along with tumor grade and reflected lymph node involvement. Novel oxicam analogues with arylpiperazine moiety at the thiazine ring were more effective in downregulating DDAHs and PRMTs and upregulating ARG2 than piroxicam and meloxicam. An analogue distinguished by propylene linker between thiazine's and piperazine's nitrogen atoms and containing two fluorine substituents was the strongest inhibitor of DDAHs and PRMTs expression, while an analogue containing propylene linker but no fluorine substituents was the strongest inhibitor of ARG2 expression. Metabolic reprogramming in CRC includes overexpression of DDAHs and PRMTs in addition to ARG1 and NOS2 and is not restricted to tumor tissue but can be modulated by novel oxicam analogues.