The assessment of Dickkopf-1 and Dickkopf-2 protein concentration in different subtypes of non-small cell lung cancer subtypes.

Introduction: Lung cancer is one of the most prevalent cancers worldwide. Dickkopf-1 (DKK-1) and -2 (DKK-2) are important proteins for the regulated Wnt signalling pathway. Alternations in the Wnt pathway are associated with tumour progression. The aim of the study was to analyse the concentration of DKK-1 and DKK-2 in tumour and matched non-tumour (NT) samples of 65 patients with non-small cell lung cancer (NSCLC), including 3 subtypes: adenocarcinoma (AC), squamous cell carcinoma (SCC), and large cell carcinoma (LCC). Material and methods: The protein concentration was measured by enzyme-linked immunosorbent assay (ELISA) in homogenates. Results: The difference between the level of DKK-1 in tumour and NT specimens was not significant for the whole NSCLC group and SCC and LCC subtype, while in AC samples they were significantly higher (p = 0.028). The highest concentration of DKK-1 was found in the advanced NSCLC samples, with the T4 parameter as well as stage III. Significantly decreased DKK-2 concentrations were detected in all NSCLC subtypes (p < 0.05). Moreover, the DKK-2 level was higher in non-smokers than in smokers. The results indicate that concentrations of DKKs were different in relation to subtypes as well as clinical and socio-demographic parameters. The concentration of DKKs could be associated with the progression of NSCLC. Conclusions: We suggest that DKK-1 could play an oncogenic role in AC, while DKK-2 could be a tumour suppressor in all NSCLC subtypes. Dickkopf-1 and DKK-2 proteins could have differential roles in the Wnt signalling pathway, which is important in many cellular processes, such as proliferation and apoptosis.

Sequencing Analysis of MUC6 and MUC16 Gene Fragments in Patients with Oropharyngeal Squamous Cell Carcinoma Reveals Novel Mutations: A Preliminary Study.

The growing incidence of oropharyngeal squamous cell carcinoma (OPSCC) calls for better understanding of the mutational landscape of such cases. Mucins (MUCs) are multifunctional glycoproteins expressed by the epithelial cells and may be associated with the epithelial tumour invasion and progression. The present study aimed at the analysis of the sequence of selected MUC6 and MUC16 gene fragments in the tumour, as well as the margin, samples obtained from 18 OPSCC patients. Possible associations between the detected mutations and the clinicopathological and demographic characteristics of the study group were analysed. Sanger sequencing and bioinformatic data analysis of the selected MUC6 and MUC16 cDNA fragments were performed. Our study found 13 and 3 mutations in MUC6 and MUC16, respectively. In particular, one novelty variant found that the MUC6 gene (chr11:1018257 A>T) was the most frequent across our cohort, in both the tumour and the margin samples, and was then classified as a high impact, stop-gain mutation. The current study found novel mutations in MUC6 and MUC16 providing new insight into the genetic alternation in mucin genes among the OPSCC patients. Further studies, including larger cohorts, are recommended to recognise the pattern in which the mutations affect oropharyngeal carcinogenesis.

The Potential Association between E2F2, MDM2 and p16 Protein Concentration and Selected Sociodemographic and Clinicopathological Characteristics of Patients with Oral Squamous Cell Carcinoma.

BACKGROUND: E2F transcription factor 2 (E2F2), murine double minute 2 (MDM2) and p16 are some of the key proteins associated with the control of the cell cycle. The aim of this study was to evaluate E2F2, MDM2 and p16 concentrations in the tumour and margin samples of oral squamous cell carcinoma and to assess their association with some selected sociodemographic and clinicopathological characteristics of the patients. METHODS: The study group consisted of 73 patients. Protein concentrations were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: There were no statistically significant differences in the levels of E2F2, MDM2 or p16 in the tumour samples as compared to the margin specimens. We found that patients with N0 showed significantly lower E2F2 concentrations than patients with N1 in the tumour samples and the median protein concentration of E2F2 was higher in HPV-negative patients in the tumour samples. Moreover, the level of p16 in the margin samples was lower in alcohol drinkers as compared to non-drinkers. Similar observations were found in concurrent drinkers and smokers compared to non-drinkers and non-smokers. CONCLUSIONS: E2F2 could potentially promote tumour progression and metastasis. Moreover, our results showed a differential level of the analysed proteins in response to alcohol consumption and the HPV status.

miR-125b-5p, miR-155-3p, and miR-214-5p and Target E2F2 Gene in Oral Squamous Cell Carcinoma.

It is known that E2F2 (E2F transcription factor 2) plays an important role as controller in the cell cycle. This study aimed to analyse the expression of the E2F2 gene and E2F2 protein and demonstrate E2F2 target microRNAs (miRNAs) candidates (miR-125b-5p, miR-155-3p, and miR-214-5p) in oral squamous cell carcinoma tumour and margin samples. The study group consisted 50 patients. The E2F2 gene and miRNAs expression levels were assessed by qPCR, while the E2F2 protein was assessed by ELISA. When analysing the effect of miRNAs expression on E2F2 gene expression and E2F2 protein level, we observed no statistically significant correlations. miR-125b-5p was downregulated, while miR-155-3p, and miR-214-5p were upregulated in tumour samples compared to margin. We observed a difference between the miR-125b-5p expression level in smokers and non-smokers in margin samples. Furthermore, HPV-positive individuals had a significantly higher miR-125b-5p and miR-214-5p expression level compared to HPV-negative patients in tumour samples. The study result showed that the E2F2 gene is not the target for analysed miRNAs in OSCC. Moreover, miR-155-3p and miR-125b-5p could play roles in the pathogenesis of OSCC. A differential expression of the analysed miRNAs was observed in response to tobacco smoke and HPV status.

Is Aberrant DNA Methylation a Key Factor in Molar Incisor Hypomineralization?

Molar incisor hypomineralization (MIH) is a qualitative disturbance of the enamel of the permanent molars and/or incisors. Its etiology is not clearly defined but is connected with different factors occurring before and after birth. It remains difficult to identify a single factor or group of factors, and the problem is further complicated by various overlapping mechanisms. In this study, we attempted to determine whether DNA methylation-an epigenetic mechanism-plays a key role in the etiology of MIH. We collected the epithelium of the oral mucosa from children with MIH and healthy individuals and analyzed its global DNA methylation level in each child using a 5-mC DNA ELISA kit after DNA isolation. There was no statistically significant difference between the global DNA methylation levels in the study and control groups. Then, we also analyzed the associations of the DNA methylation levels with different prenatal, perinatal, and postnatal factors, using appropriate statistical methods. Factors such as number of pregnancies, number of births, type of delivery, varicella infection (under 3 years old), and high fever (under 3 years old) were significantly important. This work can be seen as the first step towards further studies of the epigenetic background of the MIH etiology.

Expression of miRNA-Targeted and Not-Targeted Reporter Genes Shows Mutual Influence and Intercellular Specificity.

The regulation of translation by RNA-induced silencing complexes (RISCs) composed of Argonaute proteins and micro-RNAs is well established; however, the mechanisms underlying specific cellular responses to miRNAs and how specific complexes arise are not completely clear. To explore these questions, we performed experiments with Renilla and firefly luciferase reporter genes transfected in a psiCHECK-2 plasmid into human HCT116 or Me45 cells, where only the Renilla gene contained sequences targeted by microRNAs (miRNAs) in the 3'UTR. The effects of targeting were miRNA-specific; miRNA-21-5p caused strong inhibition of translation, whereas miRNA-24-3p or Let-7 family caused no change or an increase in reporter Renilla luciferase synthesis. The mRNA-protein complexes formed by transcripts regulated by different miRNAs differed from each other and were different in different cell types, as shown by sucrose gradient centrifugation. Unexpectedly, the presence of miRNA targets on Renilla transcripts also affected the expression of the co-transfected but non-targeted firefly luciferase gene in both cell types. Renilla and firefly transcripts were found in the same sucrose gradient fractions and specific anti-miRNA oligoribonucleotides, which influenced the expression of the Renilla gene, and also influenced that of firefly gene. These results suggest that, in addition to targeted transcripts, miRNAs may also modulate the expression of non-targeted transcripts, and using the latter to normalize the results may cause bias. We discuss some hypothetical mechanisms which could explain the observed miRNA-induced effects.

Molecular Detection of HPV, EBV, HSV-1, HCMV, and H. pylori Pathogens: An Evaluation among Polish Children with Molar Incisor Hypomineralization (MIH).

Molar incisor hypomineralization (MIH) is a congenital disorder of the enamel tissue, characterized by a quantitative deficiency. In childhood, infections such as EBV, HSV-1, HCMV, or H. pylori may occur and cause various diseases. This study aimed to investigate the prevalence of HPV, EBV, HSV-1, HCMV, and H. pylori infections in two groups of children: children with molar incisor hypomineralization (MIH) and a control group, using molecular methods. The study group included 47 children aged between 6-13 years who had been diagnosed with MIH. The control group consisted of 42 children. The study found that, in the MIH group, the prevalence of HPV-16 was 6.38%, HPV-18 was 4.26%, EBV was 31.91%, HSV-1 was 4.26%, HCMV was 4.26%, and H. pylori was 12.77%. There were no significant differences in the prevalence of any of tested pathogens between the study and the control group (p > 0.05). However, the study found a higher prevalence of EBV infection in children who had smallpox/pneumonia by the age of 3 years. Ten children were found to have at least two pathogens present. Moreover, both groups had a high prevalence and activity of EBV. These findings provide new insights into the carriage of pathogens among children with MIH, providing new information for parents, scientists, and healthcare professionals.

Transforming growth factors ß and their signaling pathway in renal cell carcinoma and peritumoral space-transcriptome analysis.

PURPOSE: The aim of the study was to verify hypotheses: Are transforming growth factors TGFß1-3, their receptors TGFßI-III, and intracellular messenger proteins Smad1-7 involved in the pathogenesis of kidney cancer? What is the expression of genes of the TGFß/Smads pathway in renal cell carcinoma (RCC) tissues, peritumoral tissues (TME; tumor microenvironment), and in normal kidney (NK) tissue?. METHODS: Twenty patients with RCC who underwent total nephrectomy were included into the molecular analysis. The mRNA expression of the genes was quantified by RT-qPCR. RESULTS: The study showed that the expression of the genes of TGFß/Smads pathway is dysregulated in both RCC and the TME: TGFß1, TGFß3 expression is increased in the TME in comparison to the NK tissues; TGFß2, TGFß3, TGFßRI, TGFßRIII, Smad1, Smad2, Smad3, and Smad6 are underexpressed in RCC comparing to the TME tissues; TGFßRI, TGFßRIII, and Smad2 are underexpressed in RCC in comparison to the NK tissues. CONCLUSION: On the one hand, the underexpression of the TGFß signaling pathway genes within the malignant tumor may result in the loss of the antiproliferative and pro-apoptotic activity of this cytokine. On the other hand, the overexpression of the TGFß/Smads pathway genes in the TME than in tumor or NK tissues most probably results in an immunosuppressive effect in the space surrounding the tumor and may have an antiproliferative and pro-apoptotic effect on non-neoplastic cells present in the TME. The functional and morphological consistency of this area may determine the aggressiveness of the tumor and the time in which the neoplastic process will spread.

Selected SNPs of FCN2 Associated with Chronic Tonsillitis in the Polish Adult Population.

Chronic tonsillitis is a problem related to bacterial and viral infections. Ficolins play a key role in the defence against various pathogens. In the present study, we investigated the associations between the selected single nucleotide polymorphisms (SNPs) of the FCN2 gene and chronic tonsillitis in the Polish population. The study included 101 patients with chronic tonsillitis and 101 healthy individuals. The selected SNPs of FCN2 (rs3124953, rs17514136 and rs3124954) were genotyped using TaqMan SNP Genotyping Assays (Applied Biosystem, Foster City, CA, USA). The analysis of rs17514136 and rs3124953 showed no significant differences in genotype frequencies between the chronic tonsillitis patients and controls (p > 0.01). The CT genotype of rs3124954 was significantly more frequent, while the CC genotype was less frequent in chronic tonsillitis patients (p = 0.003 and p = 0.001, respectively). The frequency of the A/G/T haplotype (rs17514136/rs3124953/rs3124954) was significantly more common in chronic tonsillitis patients (p = 0.0011). Moreover, the FCN2 CT genotype of rs3124954 was associated with a higher risk of chronic tonsillitis, while the CC genotype of rs3124954 decreased this risk. Our findings demonstrate that FCN2 rs3124954 may be associated with chronic tonsillitis in the Polish adult population.

Concentration of Secreted Frizzled-Related Proteins (SFRPs) in Non-Small Cell Lung Carcinoma Subtypes-A Preliminary Study.

Non-small cell lung carcinoma (NSCLC) is the most common lung cancer worldwide. Secreted frizzled-related proteins (SFRPs) are important tumour suppressors and antagonists of the Wnt signalling pathway, which is linked with cancer development. The aim of this study was to evaluate the concentrations of SFRP1, SFRP2, and SFRP5 proteins in tumour and non-tumour (NT) samples obtained from 65 patients with primary NSCLC. An enzyme-linked immunosorbent assay (ELISA) was used to measure the concentrations of SFRPs in the tissue homogenates. A significantly lower SFRP2 protein concentration was found in the total NSCLC tumour samples and the following NSCLC subtypes: squamous cell carcinoma (SCC) and adenocarcinoma (AC) (p > 0.05, p = 0.028 and p = 0.001, respectively). AC tumour samples had a higher SFRP1 level than NT samples (p = 0.022), while the highest SFRP1 concentration was found in NSCLC samples from patients with clinical stage T4 cancer. Increased concentrations of SFRP1 and SFRP5 were present in stage III NSCLC samples, while the tumour samples with high pleural invasion (PL2) had an increased level of SFRP2. The results from this study suggest that the tumour suppressor or oncogenic roles of SFRPs could be connected with the NSCLC subtype. The levels of SFRPs varied according to the clinicopathological parameters of NSCLC.

Low Prevalence of HSV-1 and Helicobacter pylori in HNSCC and Chronic Tonsillitis Patients Compared to Healthy Individuals.

Recent studies identified viral and bacterial factors, including HSV-1 and H. pylori, as possible factors associated with diseases such as chronic tonsillitis and cancers, including head and neck squamous cell carcinoma (HNSCC). We assessed the prevalence of HSV-1/2 and H. pylori in patients with HNSCC, chronic tonsillitis, and healthy individuals using PCR after DNA isolation. Associations were sought between the presence of HSV-1, H. pylori, and clinicopathological and demographic characteristics and stimulant use. HSV-1 and H. pylori were most frequently identified in controls (HSV-1: 12.5% and H. pylori: 6.3%). There were 7 (7.8%) and 8 (8.6%) patients with positive HSV-1 in HNSCC and chronic tonsillitis patients, respectively, while the prevalence of H. pylori was 0/90 (0%) and 3/93 (3.2%), respectively. More cases of HSV-1 were observed in older individuals in the control group. All positive HSV-1 cases in the HNSCC group were associated with advanced tumor stage (T3/T4). The prevalence of HSV-1 and H. pylori was highest in the controls compared to HNSCC and chronic tonsillitis patients, which indicates that the pathogens were not risk factors. However, since all positive HSV-1 cases in the HNSCC group were observed only in patients with advanced tumor stage, we suggested a possible link between HSV-1 and tumor progression. Further follow-up of the study groups is planned.

Concomitant diverticulosis among patients undergoing liver transplantation. Does it influence the length of hospitalization after the procedure?

Aim of the study: We tried to assess the influence of concomitant diverticulosis and other factors, e.g., Child-Pugh (C-P) and MELD scores, viral etiology, and presence of alcoholic disease, on short-term results of liver transplantation (LT) with an emphasis on duration of patient's hospitalization. Material and methods: This prospective study was performed on 206 cirrhotic patients who were selected for LT. In order to assess the presence of diverticculosis we performed colonoscopy. Results: The duration of hospitalization after LT did not differ significantly between patients with and without diverticulosis (27.5 [21.0-33.5] vs. 24.0 [18.0-32.0] days, p = 0.28). Patients with C-P class C were hospitalized longer in comparison to the class B patients. It is reflected in the positive correlation between C-P score and days of hospitalization (r = 0.22, p = 0.002). Patients with diverticulosis were significantly older (59.6 [51.1-63.3] vs. 52.9 [43.8-59.2] years, p = 0.03). Alcoholic liver disease (ALD) was associated with a greater risk of diverticulosis (OR = 3.89, 95% CI [1.13-15.87], p = 0.04). Conclusions: Presence of diverticulosis among subjects undergoing LT did not influence the duration of hospitalization after the procedure. Significantly longer hospitalization was observed in patients with the most advanced liver disease according to C-P score. To determine the exact impact of diverticulosis on short-term results of LT additional studies are required.

The Analysis of Selected miRNAs and Target MDM2 Gene Expression in Oral Squamous Cell Carcinoma.

MiRNAs could play an important role in tumorigenesis and progression. The oncoprotein MDM2 (murine double minute 2) was identified as a negative regulator of the tumour suppressor p53. This study aims to analyse the expression of the MDM2 target miRNA candidates (miR-3613-3p, miR-371b-5p and miR-3658) and the MDM2 gene in oral squamous cell carcinoma tumour and margin samples and their association with the selected socio-demographic and clinicopathological characteristics. The study group consisted of 50 patients. The miRNAs and MDM2 gene expression levels were assessed by qPCR. The expression analysis of the miRNAs showed the expression of only one of them, i.e., miR-3613-3p. We found no statistically significant differences in the miR-3613-3p expression in tumour samples compared to the margin samples. When analysing the effect of smoking on miR-3613-3p expression, we demonstrated a statistically significant difference between smokers and non-smokers. In addition, we showed an association between the miR-3613-3p expression level and some clinical parameters in tumour samples (T, N and G). Our study demonstrates that miR-3613-3p overexpression is involved in the tumour progression of OSCC. This indicates that miR-3613-3p possesses potential prognostic values.

Involvement of miRNAs in cellular responses to radiation.

PURPOSE: Exposure of living cells to ionizing radiation has different consequences, depending on the dose and cell type. Changes in gene expression at the level of transcription and translation, including those regulated by microRNAs (miRNAs), play a role in the intrinsic radiosensitivity of different cells and define their fate, survival or death. The aim of our work was to examine how ionizing radiation may influence the expression of genes regulated by different miRNAs and miRNA biogenesis. MATERIALS AND METHODS: The work was performed on cultured human melanoma Me45 cells, transiently transfected with plasmids containing Renilla luciferase reporter gene targeted by miRNAs Let-7, miR-21 or miR-24. The levels of reporter mRNAs and mRNAs coding for proteins participating in miRNA biogenesis were assayed at different time points in irradiated and non-irradiated cells using RT-qPCR, and reporter protein by luciferase activity assays. MiRNA-targeted motifs in mRNAs coding for proteins engaged in miRNA biogenesis were extracted from the miRTarBase database. RESULTS: Messenger RNA and protein levels of transfected luciferase genes fluctuated in time in patterns that depended on the type of miRNA regulation and changed upon irradiation of the cells. The average levels of reporter mRNAs were higher in irradiated cells, whereas the levels of proteins changed in either direction. Radiation also influenced the levels of miRNAs and the expression of genes engaged in their biogenesis suggesting that the changes in gene expression following ionizing radiation result mainly from these changes in expression of genes regulating miRNA biogenesis and the influence of miRNA on mRNA translation. CONCLUSIONS: Currently, the responses of cells to ionizing radiation are mainly ascribed to changes in their redox conditions and increased intracellular levels of ROS, but the experiments described here suggest that a further important factor is modulation of translation through changes in biogenesis and levels of miRNAs.

Single Nucleotide Polymorphism and mRNA Expression of LTF in Oral Squamous Cell Carcinoma.

Oral squamous cell carcinoma (OSCC) is one of the most prevalent types of cancers worldwide. LTF arrests the G1 to S phase transition of the cell cycle. This study is the first that has aimed to determine the possible association between the LTF polymorphisms (rs2073495, rs1126478, rs34827868, rs1042073, rs4637321, rs2239692 and rs10865941), the mRNA LTF expression, the risk of OSCC and the influence on the TNM staging and histological grading. This study was composed of 176 Polish patients, including 88 subjects diagnosed with OSCC and 88 healthy individuals. QuantStudio Design and Analysis Software v1.5.1 was used for the single nucleotide polymorphism (SNP) analysis and mRNA LTF expression. The G/G genotype of rs2073495 and the G/G genotype of rs4637321 were linked, with an increased risk of OSCC. There were no significant influences between the TNM staging and the histological grading and the LTF genotype. We found no statistically significant dissimilarities in the expression level of LTF genes in the tumour and margin specimens. No association was found between the gene expression levels, the other parameters or LTF polymorphisms in the tumour and margin samples. In conclusion, rs2073495 and rs4637321 polymorphisms may affect the risk of OSCC. These results should be validated on larger and different cohorts to better comprehend the role of the LTF gene in OSCC.

Hepatocellular cancer cell lines, Hep-3B and Hep-G2 display the pleiotropic response to resveratrol and berberine.

PURPOSE: Human carcinoma cells with different p53 status exposed to a combination of bioactive substances, resveratrol and berberine, revealed different responses in cell viability via p53-dependant apoptosis pathway activation. MATERIALS AND METHODS: Using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay, we investigated various and opposing effects in hepatocellular carcinoma cells, Hep-G2 and Hep-3B with different p53-status. RESULTS: Cells decreased in viability after treatment with dose-dependent concentrations of resveratrol and berberine. Hep-3B p53 mutants were more sensitive in comparison to the p53 wild type Hep-G2 cell line. A synergistic effect was observed after treatment of Hep-3B cells with a combination of resveratrol/berberine ratios in favor of resveratrol (2:1, 3:1). The results suggest that an effective concentration of berberine, in the presence of resveratrol, could be decreased even to 50% (half the IC50 for berberine) in cancer treatment. Combined treatment with berberine and resveratrol, at the investigated concentrations and fractions, significantly reduces the viability of wild type p53 Hep-G2 and null p53-mutant Hep-3B cells by 20% and 40%, respectively. CONCLUSIONS: Stronger toxic effects on viability and proliferation were observed in Hep-3B cells what is consistent with the assumptions that null p53-mutants activate apoptosis canonical pathway. In conclusion, p53 status in human hepatocellular cancer cell lines modulates responses to plant-derived therapies.

Influence of ursodeoxycholic acid therapy on levels of fibroblast growth factor 21, adiponectin and biochemical parameters in intrahepatic cholestasis of pregnancy.

The aim was to assess whether fibroblast growth factor 21 (FGF-21) and adiponectin influence intrahepatic cholestasis of pregnancy (ICP) pathogenesis and whether ursodeoxycholic acid (UDCA) has an impact on their levels. 50 pregnant women with ICP (ICP PW), 50 with uncomplicated pregnancy (HPW) and 50 healthy nonpregnant women (HW) were included. In ICP PW the first blood sample was drawn at the time of diagnosis, while in HPW it was drawn in the 28th week of pregnancy. The next blood samples were drawn in the 32nd and 36th week of pregnancy and one day after delivery. UDCA was administered when ICP was diagnosed. In ICP PW serum FGF-21 concentration was the lowest at the time of diagnosis with an evident increase after UDCA administration. Serum FGF-21 levels were significantly higher in ICP PW than in HPW from the first to the last measurement. There was a negative association between adiponectin and bile acids (BAs) levels in the later stage of pregnancy in ICP PW. Up-regulated FGF-21 serum levels in ICP patients compared to HPW persisted after delivery, suggesting its role in disease pathophysiology. The negative association between serum adiponectin and BAs of the later stage of pregnancy may suggest its role in regulation of BAs concentration. UDCA exerts a beneficial effect on insulin sensitivity and up-regulates FGF-21 in ICP.

Fetuin-A Deficiency but Not Pentraxin 3, FGF-21, or Irisin, Predisposes to More Serious COVID-19 Course.

Analysis of liver biopsy specimens showed that SARS-CoV-2 might have led to liver damage. This study aimed to evaluate the role of selected hepatokines and myokines in the development and progression of COVID-19. Seventy patients with laboratory-confirmed COVID-19 and 20 healthy volunteers were enrolled in the study. Irisin, pentraxin 3, fetuin-A, and FGF-21 serum concentrations and biochemical parameters were assessed using an immunoenzymatic method with commercially available enzyme immunoassay (EIA) or enzyme-linked immunosorbent assay (ELISA) kits. Serum fetuin-A concentrations were significantly decreased in COVID-19 patients compared to healthy volunteers. The serum concentration of FGF-21 was significantly increased in obese COVID-19 patients compared to overweight ones. Moreover, the FGF-21 level was higher in COVID-19 patients diagnosed with metabolic syndrome than in patients without metabolic syndrome. PTX3 concentration was higher in COVID-19 patients with higher HOMA-IR values than those with lower HOMA-IR values. COVID-19 patients with HOMA-IR ≤ 3 and >3 had significantly lower fetuin-A levels than the control group. Irisin concentration was significantly decreased in the HOMA-IR ≤ 3 COVID-19 subgroup when comparing with the control group. Lower levels of fetuin-A observed in COVID-19 patients despite higher HOMA-IR, CRP, and ferritin levels, pneumonia, patients requiring ICU care suggests that fetuin-A deficiency predisposes to more severe COVID-19 course. Upregulated pentraxin 3 may be used as a potential predictor of COVID-19 severity.

Anti-inflammatory adipokines: chemerin, vaspin, omentin concentrations and SARS-CoV-2 outcomes.

Coronavirus disease 2019 (COVID-19) is associated with systemic inflammation. A wide range of adipokines activities suggests they influence pathogenesis and infection course. The aim was to assess concentrations of chemerin, omentin, and vaspin among COVID-19 patients with an emphasis on adipokines relationship with COVID-19 severity, concomitant metabolic abnormalities and liver dysfunction. Serum chemerin, omentin and vaspin concentrations were measured in serum collected from 70 COVID-19 patients at the moment of admission to hospital, before any treatment was applied and 20 healthy controls. Serum chemerin and omentin concentrations were significantly decreased in COVID-19 patients compared to healthy volunteers (271.0 vs. 373.0 ng/ml; p < 0.001 and 482.1 vs. 814.3 ng/ml; p = 0.01, respectively). There were no correlations of analyzed adipokines with COVID-19 severity based on the presence of pneumonia, dyspnea, or necessity of Intensive Care Unit hospitalization (ICU). Liver test abnormalities did not influence adipokines levels. Elevated GGT activity was associated with ICU admission, presence of pneumonia and elevated concentrations of CRP, ferritin and interleukin 6. Chemerin and omentin depletion in COVID-19 patients suggests that this adipokines deficiency play influential role in disease pathogenesis. However, there was no relationship between lower adipokines level and frequency of COVID-19 symptoms as well as disease severity. The only predictive factor which could predispose to a more severe COVID-19 course, including the presence of pneumonia and ICU hospitalization, was GGT activity.

Quercetin as a Natural Therapeutic Candidate for the Treatment of Influenza Virus.

The medical burden caused by respiratory manifestations of influenza virus (IV) outbreak as an infectious respiratory disease is so great that governments in both developed and developing countries have allocated significant national budget toward the development of strategies for prevention, control, and treatment of this infection, which is seemingly common and treatable, but can be deadly. Frequent mutations in its genome structure often result in resistance to standard medications. Thus, new generations of treatments are critical to combat this ever-evolving infection. Plant materials and active compounds have been tested for many years, including, more recently, active compounds like flavonoids. Quercetin is a compound belonging to the flavonols class and has shown therapeutic effects against influenza virus. The focus of this review includes viral pathogenesis as well as the application of quercetin and its derivatives as a complementary therapy in controlling influenza and its related symptoms based on the targets. We also touch on the potential of this class of compounds for treatment of SARS-COV-2, the cause of new pandemic.