Exploring the Anticancer Potential of Semisynthetic Derivatives of 7α-Acetoxy-6ß-hydroxyroyleanone from Plectranthus sp.: An In Silico Approach.

The diterpene 7α-acetoxy-6ß-hydroxyroyleanone isolated from Plectranthus grandidentatus demonstrates promising antibacterial, anti-inflammatory and anticancer properties. However, its bioactivity may be enhanced via strategic structural modifications of such natural products through semisynthesis. The anticancer potential of 7α-acetoxy-6ß-hydroxyroyleanone and five derivatives was analyzed in silico via the prediction of chemicals absorption, distribution, metabolism, excretion, and toxicity (ADMET), quantum mechanical calculations, molecular docking and molecular dynamic simulation. The protein targets included regulators of apoptosis and cell proliferation. Additionally, network pharmacology was used to identify potential targets and signaling pathways. Derivatives 7α-acetoxy-6ß-hydroxy-12-O-(2-fluoryl)royleanone and 7α-acetoxy-6ß-(4-fluoro)benzoxy-12-O-(4-fluoro)benzoylroyleanone achieved high predicted binding affinities towards their respective protein panels, with stable molecular dynamics trajectories. Both compounds demonstrated favorable ADMET parameters and toxicity profiles. Their stability and reactivity were confirmed via geometry optimization. Network analysis revealed their involvement in cancer-related pathways. Our findings justify the inclusion of 7α-acetoxy-6ß-hydroxy-12-O-(2-fluoryl)royleanone and 7α-acetoxy-6ß-(4-fluoro)benzoxy-12-O-(4-fluoro)benzoylroyleanone in in vitro analyses as prospective anticancer agents. Our binding mode analysis and stability simulations indicate their potential as selective inhibitors. The data will guide studies into their structure optimization, enhancing efficacy and drug-likeness.

Serum IL-5, POSTN and IL-33 levels in chronic rhinosinusitis with nasal polyposis correlate with clinical severity.

BACKGROUND: Chronic rhinosinusitis (CRS) is a group of heterogeneous diseases characterized by epithelial inflammation and tissue eosinophilic infiltration. IL-5, POSTN, and IL-33 are important factors that act as chemoattractants for eosinophils, and a tissue-remodeling protein positively correlated with eosinophils in blood and mediators of eosinophilic infiltration. The aim of the study was to determine the expression of IL-5, POSTN and IL-33, at the gene and protein levels, in eosinophilic CRS with nasal polyps (CRSwNP) and without nasal polyps (CRSsNP), and to correlate this expression with clinical severity. MATERIALS AND METHODS: The study included 40 CRSwNP patients and 53 CRSsNP patients and 40 control subjects. The expression of IL-5, POSTN and IL-33 mRNA was determined in sinonasal mucosal samples and in nasal polyp tissue by real-time PCR. Protein levels in the serum of CRSwNP patients were measured by ELISA. Computed tomography was evaluated according to Lund-Mackay scores, and visual analog scale scores were assessed. RESULTS: NP tissue demonstrated significantly higher IL-5 and POSTN mRNA expression than the sinonasal tissue in the CRSsNP and CRSwNP groups. CRS groups demonstrated elevated IL-33 mRNA expression in comparison to controls irrespective of the presence of NP. No correlation was found between IL-5, POSTN and IL-33 mRNA expression and disease severity. CRSwNP group demonstrated significantly higher serum IL-5, POSTN and IL-33 protein levels than controls, and this corresponds to disease severity. CONCLUSION: Serum IL-5, POSTN and IL-33 levels may be important markers for classification of eosinophilic CRSwNP patients, along with disease severity.

Inhibitory Effect of Eugenol and trans-Anethole Alone and in Combination with Antifungal Medicines on Candida albicans Clinical Isolates.

One of the most common pathogens among yeasts is Candida albicans, which presents a serious health threat. The study aimed to check the antifungal properties of trans-anethole and eugenol with selected antifungal medicines (AMs) against C. albicans clinical isolates. The checkerboard method was used to tests of interactions between these compounds. Achieved results indicated that eugenol showed synergistic and additive activities with miconazole and econazole against investigated clinical isolates, respectively. Moreover, the combination - trans-anethole - miconazole also showed an additive effect against two clinical isolate. We tried to relate the results to changes in C. albicans cell sheaths under the influence of essential oils compounds (EOCs) performing the Fourier transform infrared spectra analysis to confirm the presence of particular chemical moieties in C. albicans cells. Nevertheless, no strong relationships was observed between synergistic and additive actions of used EOC-AMs combinations and chemical moieties in C. albicans cells.

A Summary of In Vitro and In Vivo Studies Evaluating the Impact of E-Cigarette Exposure on Living Organisms and the Environment.

Worldwide use of electronic cigarettes has been rapidly expanding over recent years, but the long-term effect of e-cigarette vapor exposure on human health and environment is not well established; however, its mechanism of action entails the production of reactive oxygen species and trace metals, and the exacerbation of inflammation, which are associated with potential cytotoxicity and genotoxicity. The present study examines the effects of selected liquid chemicals used in e-cigarettes, such as propylene glycol/vegetable glycerin, nicotine and flavorings, on living organisms; the data collected indicates that exposure to e-cigarette liquid has potentially detrimental effects on cells in vitro, and on animals and humans in vivo. While e-liquid exposure can adversely influence the physiology of living organisms, vaping is recommended as an alternative for tobacco smoking. The study also compares the impact of e-cigarette liquid exposure and traditional cigarette smoke on organisms and the environmental impact. The environmental influence of e-cigarette use is closely connected with the emission of airborne particulate matter, suggesting the possibility of passive smoking. The obtained data provides an insight into the impact of nicotine delivery systems on living organisms and the environment.

Synergistic effect of fennel essential oil and hydrogen peroxide on bacterial biofilm.

INTRODUCTION: Staphylococcal biofilm formation significantly challenges wound management. The causes of difficult-to-treat wounds are not only methicillin-resistant staphylococci, but also methicillin-sensitive strains with different patterns of resistance. Bacterial biofilm significantly limits the access and activity of antimicrobials used in dermatological infections. AIM: To evaluate the synergistic effect of fennel essential oil (FEO) and H2O2 on biofilm formation by Staphylococcus aureus (MSSA and MRSA) reference strains. MATERIAL AND METHODS: Minimum inhibitory concentration (MIC) values were determined for FEO and H2O2 against S. aureus reference strains by the broth microdilution method. The combined effects of the FEO and H2O2 were calculated and expressed in terms of a fractional inhibitory concentration index (FICI) using the checkerboard method. The FEO composition was analyzed by the GC-MS method. The data were analysed by one-way ANOVA. RESULTS: Decreased MIC values for FEO combined with H2O2 were observed in comparison to FEO itself. The combinations of FEO and H2O2 determined synergistic effects on all S. aureus reference strains. Subinhibitory concentration of FEO alone and in combination with 0.5 MIC of H2O2 significantly decreased the production of biofilm biomass in S. aureus strains and reduced the metabolic activity of attached cells. CONCLUSIONS: Combination of fennel essential oil containing nearly 80% trans-anethole and H2O2 represents a potential for further basic and applied research on wound management.

Abscisic Acid Regulates the 3-Hydroxy-3-methylglutaryl CoA Reductase Gene Promoter and Ginsenoside Production in Panax quinquefolium Hairy Root Cultures.

Panax quinquefolium hairy root cultures synthesize triterpenoid saponins named ginsenosides, that have multidirectional pharmacological activity. The first rate-limiting enzyme in the process of their biosynthesis is 3-hydroxy-3-methylglutaryl CoA reductase (HMGR). In this study, a 741 bp fragment of the P. quinquefolium HMGR gene (PqHMGR), consisting of a proximal promoter, 5'UTR (5' untranslated region) and 5'CDS (coding DNA sequence) was isolated. In silico analysis of an isolated fragment indicated a lack of tandem repeats, miRNA binding sites, and CpG/CpNpG elements. However, the proximal promoter contained potential cis-elements involved in the response to light, salicylic, and abscisic acid (ABA) that was represented by the motif ABRE (TACGTG). The functional significance of ABA on P. quinquefolium HMGR gene expression was evaluated, carrying out quantitative RT-PCR experiments at different ABA concentrations (0.1, 0.25, 0.5, and 1 mg·L-1). Additionally, the effect of abscisic acid and its time exposure on biomass and ginsenoside level in Panax quinquefolium hairy root was examined. The saponin content was determined using HPLC. The 28 day elicitation period with 1 mg·L-1 ABA was the most efficient for Rg2 and Re (17.38 and 1.83 times increase, respectively) accumulation; however, the protopanaxadiol derivative content decreased in these conditions.

Plant Extracts and Reactive Oxygen Species as Two Counteracting Agents with Anti- and Pro-Obesity Properties.

Obesity is a complex disease of great public health significance worldwide: It entails several complications including diabetes mellitus type 2, cardiovascular dysfunction and hypertension, and its prevalence is increasing around the world. The pathogenesis of obesity is closely related to reactive oxygen species. The role of reactive oxygen species as regulatory factors in mitochondrial activity in obese subjects, molecules taking part in inflammation processes linked to excessive size and number of adipocytes, and as agents governing the energy balance in hypothalamus neurons has been examined. Phytotherapy is the traditional form of treating health problems using plant-derived medications. Some plant extracts are known to act as anti-obesity agents and have been screened in in vitro models based on the inhibition of lipid accumulation in 3T3-L1 cells and activity of pancreatic lipase methods and in in vivo high-fat diet-induced obesity rat/mouse models and human models. Plant products may be a good natural alternative for weight management and a source of numerous biologically-active chemicals, including antioxidant polyphenols that can counteract the oxidative stress associated with obesity. This review presents polyphenols as natural complementary therapy, and a good nutritional strategy, for treating obesity without serious side effects.

The Antibacterial Activity of Lavender Essential Oil Alone and In Combination with Octenidine Dihydrochloride against MRSA Strains.

In the post-antibiotic era the issue of bacterial resistance refers not only to antibiotics themselves but also to common antiseptics like octenidine dihydrochloride (OCT). This appears as an emerging challenge in terms of preventing staphylococcal infections, which are both potentially severe and easy to transfer horizontally. Essential oils have shown synergisms both with antibiotics and antiseptics. Therefore the aim of this study was to investigate the impact of lavender essential oil (LEO) on OCT efficiency towards methicillin-resistant S. aureus strains (MRSA). The LEO analyzed in this study increased the OCT's susceptibility against MRSA strains. Subsequent FTIR analysis revealed cellular wall modifications in MRSA strain cultured in media supplemented with OCT or LEO/OCT. In conclusion, LEO appears to be a promising candidate for an efficient enhancer of conventional antiseptics.

Impaired resolution of wheals in the skin prick test and low diamine oxidase blood level in allergic patients.

INTRODUCTION: Histamine is the major mediator of IgE- and non-IgE-mediated allergic reactions upon allergen or hapten contact. Reduced histamine degradation capacity was associated with atopic eczema as well as with non-immunological histamine intolerance. Higher blood serum histamine level concomitant with decreased intestinal diamine oxidase activity were observed in patients with food allergy. AIM: To evaluate the relationship between patients' blood diamine oxidase (DAO) activity/histamine status and their reactivity to time-resolved histamine skin prick test in respect to vulnerability to allergic diseases. MATERIAL AND METHODS: Fifty-three patients were examined with skin prick tests (SPT) and patch tests for suspected presence of either IgE- or non-IgE-mediated allergy. All individuals were skin prick tested with histamine and the resolution of the wheal was monitored for 50 min. Blood DAO activity and histamine concentration were measured with a radio-extraction radioimmunoassay. RESULTS: Time-resolved histamine skin prick testing revealed presence of wheals which were 35% larger in diameter in 47% of examined subjects at 20 min of the test. These patients exhibited significantly compromised time-course wheal resolution (wheal ≥ 3 mm at 50 min) compared to a group of patients with the normal-rate of wheal resolution (wheal = 0 mm at 50 min). Within a group of subjects exhibiting impaired wheal resolution, 61% of patients were diagnosed allergic compared to 50% in a group of patients with a normal rate of wheal resolution. Finally, allergic patients were characterized by a significantly lower DAO activity and higher histamine content compared to healthy subjects. CONCLUSIONS: The results of this study indicate that patients with IgE- or non-IgE-mediated allergy are likely to have low DAO blood activity and may concomitantly suffer from histamine intolerance. Furthermore, our results suggest that allergic patients are more likely to develop an excessive SPT reaction. Our results emphasize caution in interpretation of the SPT results in allergic patients with diagnosed histamine intolerance or histamine/DAO activity imbalance.

The effect of fennel essential oil and trans-anethole on antibacterial activity of mupirocin against Staphylococcus aureus isolated from asymptomatic carriers.

INTRODUCTION: Staphylococcus aureus constitutes the most pathogenic species within the staphylococcal genus. Humans remain the major reservoirs of this pathogen which colonizes mostly anterior nares of healthy individuals. AIM: To investigate the effect of fennel essential oil (FEO) and trans-anethole (tA) on antibacterial activity of mupirocin (MUP) against S. aureus strains isolated from asymptomatic carriers. MATERIAL AND METHODS: The content of the FEO was analysed with use of the GC-MS method. The research done on 43 S. aureus isolates with different resistance patterns, obtained from nasal vestibule. Antibacterial activity of MUP in combination with FEO or tA was examined using the agar dilution method and E-test method. The data analysis was done with the Pearson's χ2 test. RESULTS: The chemical composition of FEO was consistent with the European Pharmacopoeia (EP) for the main constituent - tA (77.9%) according to the EP recommendations. Macrolide-lincosamide-streptogramin B resistance phenotype was prevalent among 39.5% of S. aureus isolates. FEO concentrations of 2.0% and 2.5% revealed antibacterial activity against 76.7% of isolates, whereas tA inhibited S. aureus growth at concentrations > 4.0%. The MIC values for MUP combined with FEO as well as for MUP combined with tA were < 0.064 µg/ml for 79.1% and 86.0% of S. aureus isolates, respectively. CONCLUSIONS: Our experiment revealed FEO and tA influence on MUP effectiveness. The combination of MUP with FEO as well as MUP with tA are worth considering to implement in S. aureus eradication procedures. These findings will be useful in designing efficient antistaphylococcal agents which can limit the emergence of antibiotic resistance.

[Narrow-band imaging endoscopy for diagnosis of adult laryngeal papillomatosis - case raports].

The laryngeal papillomas belong to the group of non-malignant tumours. The risk of getting sick increases with the number of contingent sexual contacts, smoking, alcohol abuse and untreated gastro-oesophageal reflux. This paper describes five cases presenting different levels of exposure to the risk factors and variable course of adult laryngeal papillomatosis. These people, in addition to routine diagnostics, were examined using endoscopy with the use of narrow beam of light, which turns out to be a useful diagnostic tool in the case of laryngeal papillomatosis.

[Cryosurgery in the treatment of allergic and non-allergic rhinitis].

OBJECTIVE: Introduction: Pharmacological treatment of both allergic and non-allergic rhinitis is not always effective. The aim: Assessment of the effectiveness of treatment of patients with allergic and non-allergic vasomotor rhinitis using cryoablation procedures. PATIENTS AND METHODS: Material and methods: The study involved 60 patients, including 28 women and 32 men, aged 17-76 years (the average age 39) with rhinitis. All participants were assigned into two groups: I group - 18 patients with chronic allergic rhinitis; II group - 42 patients with chronic non-allergic vasomotor rhinitis. The research methodology included: anamnesis, otolaryngological physical examination, rhinomanometer test, performed before and 3 months after the procedure. The cryoablation of nasal turbinates was performed under local anesthesia,with a 1% xylocaine solution using the Cryo-S device from CryoFlex Poland. RESULTS: Results: After the cryoablation treatment, in both groups the statistically significant improvement was observed both in the subjective assessment of symptoms of nasal obstruction and in the mean rhinomanometry of air flows through the nasal passages during inspiration and exhalation. CONCLUSION: Conclusions: Cryosurgical treatment is not the first-line treatment for the treatment of allergic and non-allergic vasomotor rhinitis, it does not remove the causes of the disease. However, it may be an effective method of treatment for some patients and a supplement to existing treatment.

Effects of oral contraceptives on selected parameters of the homeostatic control system in young women having a sudden disorder of the auditory and/or balance system.

The purpose of the paper was to assess the effects of oral contraceptives on selected parameters of the homeostatic control system in women having a sudden disorder of the auditory and/or balance system. The study included 105 young women divided into two groups: Group I--52 women with the disorder of the auditory and/or balance system using hormonal contraceptives for at least 2 months, aged 20-49; and Group II--53 women without any disorder of the auditory and/or balance system using hormonal contraceptives for at least 2 months, aged 18-40. The patients included in the study underwent a full otoneurological evaluation, detailed laryngological diagnostics and an evaluation of selected parameters of the homeostatic control system--fibrinogen level, D-dimer level, evaluation of APTT and PT indicator, plasma estradiol and progesterone with the Roche Cobas analyser by means of chemiluminescence. The vertigo occurring in the study group was most often central (59.6% of cases), mixed with compensation in 36.6% of cases, and peripheral only in 3.8% of cases, indicating labyrinth damage in 40.4% of cases. An analysis of the progesterone level, considering the menstrual cycle phase in the group, showed that its value was abnormal in 51.0% of women in the study group and 47.1% in the control group. In their own studies, the authors observed that the estradiol level in the plasma, considering the menstrual cycle phase in the study group, was abnormal in 41.2% of women and that the differences in its concentration were statistically significant in the study and control groups (p = 0.005), which may have a negative impact on the possibility of a thromboembolic episode.

Significance of CYCLOOXYGENASE-2(COX-2), PERIOSTIN (POSTN) and INTERLEUKIN-4(IL-4) gene expression in the pathogenesis of chronic rhinosinusitis with nasal polyps.

The purpose of this paper was to evaluate the level of Cyclooxygenase-2 (COX-2), Periostin (POSTN) and Interleukin-4(IL-4) gene expression in patients with chronic rhinosinusitis with nasal polyps, without polyps and with a nasal septum deviation. The tests were performed on 63 patients (24 women and 39 men) with chronic rhinosinusitis and polyps (CRSwP-study group I), with determination of the COX-2, POSTN and IL-4 gene expression; an allergy was diagnosed in 38 cases. The reference groups were patients with chronic rhinosinusitis without polyps--CRS (n = 23, including 14 women and 9 men) and patients with nasal septum deviation--DSN (n = 18, including 9 women and 9 men). The expression level was determined in the polyp tissue and the mucosa of paranasal sinus collected during an FESS. The expression level of studied genes was also evaluated in the material. Immediately after being collected, the tissue fragments were placed in test tubes with 1 ml of RNAlater (Qiagen, Hilden, Germany) preventing the degradation of RNA and frozen at -70 °C. The studies revealed an increased level of POSTN, IL-4 gene expression and a decreased level of COX-2 gene expression that may be associated with the development of chronic rhinosinusitis with nasal polyps. An analysis of the expression level indicates the participation of POSTN and IL-4 in the development of chronic rhinosinusitis with nasal polyps in patients with atopy.

Association of IL1ß and IL4 gene polymorphisms with nasal polyps in a Polish population.

Imbalance between proinflammatory and anti-inflammatory cytokines may regulate the inflammatory reaction in the nasal polyps. Polymorphisms in the regulatory regions of the cytokines genes may influence their expression. The aim of this study was to investigate the relationship between an IL-1ß and IL-4 promoter polymorphisms and nasal polyps. The C-511T promoter polymorphism of the IL-1ß gene and C-590T promoter polymorphism of the IL-4 gene were genotyped by polymerase chain reaction-restriction fragment length polymorphism analysis in 208 Polish patients with nasal polyps and 200 healthy Polish subjects. The risk of susceptibility to NP was significantly higher in patients with NP who had -511 T/T genotype of IL1ß than in controls (OR 3.07; 95 % CI 1.18-7.99). No statistically significant differences were found between NP patients and the control group with regard to genotype distribution and allele frequencies of C/T polymorphism of IL4 gene. Our study demonstrated that the TT genotype for C-511T mutation associated with the risk of developing NP in a Polish population.

Effects of three different types of anaesthesia on perioperative bleeding control in functional endoscopic sinus surgery.

The aim of the study was to assess the effect of three different types of anaesthesia on perioperative bleeding control and to analyse the mean arterial blood pressure and heart rate in patients undergoing endoscopic paranasal sinus surgery. Ninety patients (30 women and 60 men, aged 18-85 years) scheduled to undergo functional endoscopic sinus surgery in the years 2008-2010 were identified as candidates for inclusion in the study. Patients were randomly assigned to one of three groups (30 patients each) according to the type of general anaesthesia to be administered. Groups I and II both received inhalation anaesthesia (sevoflurane for sedation) and intravenous anaesthesia (fentanyl in group I, remifentanil in group II). Anaesthesia was delivered solely via intravenous route (TIVA) in group III, with propofol used for sedation and remifentanil for analgesia. Blood pressure and heart rate were monitored during surgery and post-surgically for 4 h. Mean anaesthesia duration in groups I, II and III was 108.7 ± 20.8, 112.6 ± 22.2 and 103.7 ± 17.5 min and the surgery duration was 71.3 ± 16.7, 78.8 ± 24.2 and 66.5 ± 15.5 min, respectively. Mean blood loss during surgery was 365.0 ± 176.2, 340.0 ± 150.5 and 225.0 ± 91.7 ml, with a mean blood loss rate of 5.1 ± 2.4, 4.5 ± 2.2 and 3.4 ± 1.1 ml/min in groups I, II and III, respectively. Technologically advanced control of the drug dose with the TIVA technique allows for better control of perioperative bleeding.

PD-1 and PDL-1 gene expression in nasal polyp tissue from patients with asthma exacerbated by non-steroidal anti-inflammatory drugs correlates with the severity of the disease.

INTRODUCTION: The clinical syndrome that includes asthma, nasal polyps and hypersensitivity to nonsteroidal anti-inflammatory drugs is referred to as airway disease exacerbated by nonsteroidal anti-inflammatory drugs. Patients usually have the most severe form of nasal polyps. Asthma and chronic rhinosinusitis with nasal polyps share a common inflammatory profile, involving type 2 helper T lymphocytes. T-cell activity can be inhibited via the programmed death receptor, PD-1, leading to modulation of the immune response. Therefore, the purpose of this study is to evaluate the expression of genes encoding PD-1 and its ligand PD-L1 in nasal polyp tissue in patients with asthma exacerbated by non-steroidal anti-inflammatory drugs and to correlate the results with clinical data. MATERIAL AND METHODS: The material used for the study consisted of 54 tissue sections of nasal polyps. In the specimens, the expression of PD-1 and PD-L1 genes was determined at the mRNA level by qPCR. Statistical analysis was used to evaluate the results of the study. RESULTS: The expression of PD-1 and PD-L1 genes in the tissue of polyps was statistically significantly higher than in the nasal mucosa of patients in the control group. In addition, there was a correlation between the expression of both genes at the mRNA level and the severity of nasal polyps in the paranasal sinuses analyzed from computed tomography images of the paranasal sinuses and assessed using the Kennedy scale. CONCLUSIONS: Determining the expression of PD-1 and PD-L1 genes may provide a marker for the severity of polypoid lesions. In addition, learning more about the PD-1/PD-L signaling pathway and how it can be modulated may provide a potential therapeutic strategy for patients with inflammatory diseases.

Improved efficacy of eugenol and trans-anethole in combination with octenidine dihydrochloride against Candida albicans and Candida parapsilosis.

INTRODUCTION AND OBJECTIVE: Candidiasis is a fungal infection caused by yeasts from the Ogenus Candida. Considering increasing antifungal resistance rates the activity was analyzed of natural compounds to eradicate Candida spp. The aim of the study was to check the antifungal activity of selected essential oil compounds (EOCs; thymol, menthol, eugenol [E], carvacrol, trans-anethole [TA]) alone, and in combination with octenidine dihydrochloride (OCT) against C. albicans and C. parapsilosis reference, and clinical strains. MATERIAL AND METHODS: Investigated clinical isolates were obtained from skin wounds of patients treated for superficial wounds candidiasis. The following parameters were studied: antifungal susceptibility testing using the VITEK system, antifungal activity of EOCs alone and in combination with OCT using microdilution and checkerboard assays, antifungal efficacy of selected chemicals using time-kill curve assay, and changes in cell permeability in the presence of selected chemicals using crystal violet assay. RESULTS: Clinical isolates of C. albicans and C. parapsilosis were resistant to fluconazole and voriconazole. The highest inhibition activity against Candida isolates was observed for E. The OCT - TA and OCT - E combinations showed synergistic and additive activities against all strains, respectively. These combinations also appeared to affect the rate of yeast cell killing and increasing the permeability of Candida cells. CONCLUSIONS: The study indicates that E and TA potentially used in formulation with OCT might eradicate pathogenic yeasts; however, microbiological and clinical studies are still required.

PD-1 and PD-L1 Expression Levels as a Potential Biomarker of Chronic Rhinosinusitis and Head and Neck Cancers.

Inflammation is an etiological factor of various chronic diseases contributing to more than 50% of worldwide deaths. In this study, we focus on the immunosuppressive role of the programmed death-1 (PD-1) receptor and its ligand (PD-L1) in inflammatory-related diseases, including chronic rhinosinusitis and head and neck cancers. The study included 304 participants. Of this number, 162 patients had chronic rhinosinusitis with nasal polyps (CRSwNP), 40 patients had head and neck cancer (HNC) and there were 102 healthy subjects. The expression level of the PD-1 and PD-L1 genes in the tissues of the study groups was measured by qPCR and Western blot methods. The associations between the age of the patients and the extent of disease and genes' expression were evaluated. The study showed a significantly higher mRNA expression of PD-1 and PD-L1 in the tissues of both the CRSwNP and HNC patient groups compared to the healthy group. The severity of CRSwNP significantly correlated with the mRNA expression of PD-1 and PD-L1. Similarly, the age of the NHC patients influenced PD-L1 expression. In addition, a significantly higher level of PD-L1 protein was noticed also for both the CRSwNP and HNC patient groups. The increased expression of PD-1 and PD-L1 may be a potential biomarker of inflammatory-related diseases, including chronic rhinosinusitis and head and neck cancers.

Association of the -33C/G OSF-2 and the 140A/G LF gene polymorphisms with the risk of chronic rhinosinusitis with nasal polyps in a Polish population.

Nasal polyps are strongly associated with a risk of chronic rhinosinusitis development as well as other obstruction including asthma and allergy. The following study tested the association of the 140A/G polymorphism of lactoferine (LF) encoding gene and the -33C/G polymorphism of osteoblast-specific factor-2 (OSF-2) encoding gene with a risk of chronic rhinosinusitis with nasal polyps in a Polish population. One hundred ninety five patients of chronic rhinosinusitis with nasal polyps as well as 200 sex, age and ethnicity matched control subjects without chronic sinusitis and nasal polyps were enrolled in this study. Among the group of patients 63 subjects were diagnosed with allergy and 65 subjects with asthma, respectively. DNA was isolated from peripheral blood lymphocytes of patients as well as controls and gene polymorphisms were analyzed by restriction fragments length polymorphism polymerase chain reaction (RFLP-PCR). We reported that the 140A/G LF (OR 4.78; 95% CI 3.07-7.24), the -33C/G OSF-2 OR 3.48; 95% CI 2.19-5.52) and the -33G/G OSF-2 (OR 16.45; 95% CI 6.71-40.30) genotypes were associated with an increased risk of chronic rhinosinusitis with nasal polyps among analyzed group of patients. Moreover, the group of patients without allergy or asthma indicated the association of the -33C/G (OR 3.72; 95% CI 2.24-6.19 and OR 15.11; 95% CI 5.91-38.6) and -33G/G (OR 3.73; 95% CI 2.24-6.19 and OR 14.07; 95% CI 5.47-36.16) genotypes of the OSF-2 as wells as 140A/G (OR 3.89; 95% CI 2.40-6.31 and OR 3.62; 95% CI 2.45-5.34) genotype of OSF-2 with an increased risk of chronic rhinosinusitis with nasal polyps. Finally, it was also found that the selected group of patients with allergy or asthma indicated a very strong association of the -33C/G (OR 2.40; 95% CI 1.23-4.69 and OR 2.40; 95% CI 1.23-4.69, respectively) and -33G/G (OR 16.01; 95% CI 5.77-44.41 and OR 17.90; 95% CI 6.53-49.05, respectively) genotypes of the OSF-2 as wells as 140A/G (OR 3.22; 95% CI 1.74-6.11 and OR 3.25; 95% CI 1.75-6.04, respectively) genotypes with an increased risk of chronic rhinosinusitis with nasal polyps. Thus, our results suggest that LF and OSF-2 gene polymorphisms may have deep impact on the risk of rhinosinusitis nasal polyps' formation which may also depend on asthma or allergy. Our results showed that the 140A/G polymorphism of LF gene and the -33C/G polymorphism of the OSF-2 gene may be associated with the risk of chronic rhinosinusitis with nasal polyps in a Polish population.