Evaluation of differences in expression pattern of three isoforms of the transforming growth factor beta in patients with lumbosacral stenosis.

The study investigates molecular changes in the lumbosacral (L/S) spine's yellow ligamentum flavum during degenerative stenosis, focusing on the role of transforming growth factor beta 1-3 (TGF-ß-1-3). Sixty patients with degenerative stenosis and sixty control participants underwent molecular analysis using real-time quantitative reverse transcription reaction technique (RTqPCR), enzyme-linked immunosorbent assay (ELISA), Western blot, and immunohistochemical analysis (IHC). At the mRNA level, study samples showed reduced expression of TGF-ß-1 and TGF-ß-3, while TGF-ß-2 increased by only 4%. Conversely, at the protein level, the study group exhibited significantly higher concentrations of TGF-ß-1, TGF-ß-2, and TGF-ß-3 compared to controls. On the other hand, at the protein level, a statistically significant higher concentration of TGF-ß-1 was observed (2139.33 pg/mL ± 2593.72 pg/mL vs. 252.45 pg/mL ± 83.89 pg/mL; p < 0.0001), TGF-ß-2 (3104.34 pg/mL ± 1192.74 pg/mL vs. 258.86 pg/mL ± 82.98 pg/mL; p < 0.0001), TGF-ß-3 (512.75 pg/mL ± 107.36 pg/mL vs. 55.06 pg/mL ± 9.83 pg/mL, p < 0.0001) in yellow ligaments obtained from patients of the study group compared to control samples. The study did not establish a significant correlation between TGF-ß-1-3 concentrations and pain severity. The findings suggest that molecular therapy aimed at restoring the normal expression pattern of TGF-ß-1-3 could be a promising strategy for treating degenerative stenosis of the L/S spine. The study underscores the potential therapeutic significance of addressing molecular changes at the TGF-ß isoforms level for better understanding and managing degenerative spinal conditions.

Assessment of Changes in Cap and Residual Stromal Thickness Values during a 6-Month Observation after Refractive Lenticule Extraction Small Incision Lenticule Extraction.

Background: In this study, the changes in corneal cap and residual stromal thickness (RST) values during a 180-day observation period after refractive lenticule extraction small incision lenticule extraction (ReLEx SMILE) were assessed. Methods: Fifty patients underwent ReLEx SMILE using the VisuMax 500 femtosecond laser, with corneal imaging conducted pre and post procedure via anterior segment optical coherence tomography (AS-OCT). Cap thickness in the center and 1.5 mm from the center in four meridians was measured at various intervals. Results: The results showed a significant decrease in cap thickness 180 days post procedure compared to earlier intervals (p < 0.05). Similarly, RST decreased gradually and significantly post procedure (p < 0.05). Notably, changes in cap thickness within the central 1.5 mm area were more dynamic than RST changes during the 6-month observation period following SMILE. Conclusions: The corneal cap thickness measured with swept-source AS-OCT within the central 1.5 mm area underwent more dynamic changes than the residual stromal thickness during the 6-month observation following SMILE.

Expression profile of mRNAs and miRNAs related to mitogen-activated kinases in HaCaT cell culture treated with lipopolysaccharide a and adalimumab.

Studies indicate that mitogen-activated protein kinases (MAPKs) exhibit activation and overexpression within psoriatic lesions. This study aimed to investigate alterations in the expression patterns of genes encoding MAPKs and microRNA (miRNA) molecules that potentially regulate their expression in human adult low-calcium high-temperature (HaCaT) keratinocytes when exposed to bacterial lipopolysaccharide A (LPS) and adalimumab. HaCaT cells underwent treatment with 1 µg/mL LPS for 8 hours, followed by treatment with 8 µg/mL adalimumab for 2, 8, or 24 hours. Untreated cells served as controls. The molecular analysis involved microarray, quantitative real-time polymerase chain reaction (RTqPCR), and enzyme-linked immunosorbent assay (ELISA) analyses. Changes in the expression profile of seven mRNAs: dual specificity phosphatase 1 (DUSP1), dual specificity phosphatase 3 (DUSP3), dual specificity phosphatase 4 (DUSP4), mitogen-activated protein kinase 9 (MAPK9), mitogen-activated protein kinase kinase kinase 2 (MAP3K2), mitogen-activated protein kinase kinase 2 (MAP2K2), and MAP kinase-activated protein kinase 2 (MAPKAPK2, also known as MK2) in cell culture exposed to LPS or LPS and the drug compared to the control. It was noted that miR-34a may potentially regulate the activity of DUSP1, DUSP3, and DUSP4, while miR-1275 is implicated in regulating MAPK9 expression. Additionally, miR-382 and miR-3188 are potential regulators of DUSP4 levels, and miR-200-5p is involved in regulating MAPKAPK2 and MAP3K2 levels. Thus, the analysis showed that these mRNA molecules and the proteins and miRNAs they encode appear to be useful molecular markers for monitoring the efficacy of adalimumab therapy.

Serum Selenium Concentration as a Potential Diagnostic Marker for Early-Stage Colorectal Cancer: A Comparative Study.

BACKGROUND Selenium deficiency is an established risk factor for colorectal cancer. The aim of the present study was to determine selenium levels in blood samples obtained from colorectal cancer patients compared with the levels of this element in the blood of patients who had undergone hernia repair and cholecystectomy. MATERIAL AND METHODS The study group consisted of 49 patients diagnosed with colorectal cancer at our institution. The comparison group consisted of 29 and 26 patients undergoing hernia repair and cholecystectomy, respectively. The histological staging level was evaluated on a 4-grade scale. Serum selenium concentration was quantified by inductively coupled mass spectrometry using methane to reduce polyatomic interference. RESULTS Colorectal cancer patients had significantly lower serum selenium concentration than the comparison patients (67.24±15.55 µg/L vs 78.81±12.93 µg/L; P<0.001), and selenium concentration was below the reference range in a high percentage of colorectal cancer patients. However, among the colorectal cancer patients, no significant difference in cancer grading was observed according to selenium concentration (P=0.235). Serum selenium concentration in the patients was evaluated on the basis of 5 independent variables (R=0.6250): age (P=0.011), number of leukocytes (P=0.010), family history of cancer (P=0.045), dietary supplements (P=0.023), and exposure to chemical factors (P=0.057). CONCLUSIONS This study supports findings from previous studies that low serum selenium levels are associated with colorectal cancer and that selenium deficiency may be a risk factor for colorectal cancer.

Gene expression profile of mitogen-activated kinases and microRNAs controlling their expression in HaCaT cell culture treated with lipopolysaccharide A and cyclosporine A.

Studies indicate that mitogen-activated protein kinases (MAPKs) are activated and overexpressed in psoriatic lesions. The aim of the study was to assess changes in the expression pattern of genes encoding MAPKs and microRNA (miRNA) molecules potentially regulating their expression in human adult low-calcium high-temperature (HaCaT) keratinocytes exposed to bacterial lipopolysaccharide A (LPS) and cyclosporine A (CsA). HaCaT cells were treated with 1 µg/mL LPS for 8 h, followed by treatment with 100 ng/mL cyclosporine A for 2, 8, or 24 h. Untreated cells served as controls. The molecular analysis consists of microarray, quantitative real-time polymerase chain reaction, and enzyme-linked immunosorbent assay analyses. The statistical analysis of the obtained results was performed using Transcriptome Analysis Console and STATISTICA 13.5 PL with the statistical significance threshold of p < 0.05. Changes in the expression profile of six mRNAs: dual-specificity phosphatase 1 (DUSP1), dual-specificity phosphatase 4 (DUSP4), mitogen-activated protein kinase kinase 2 (MAP2K2), mitogen-activated protein kinase kinase 7 (MAP2K7), mitogen-activated protein kinase kinase kinase 2 (MAP3K2) and mitogen-activated protein kinase 9 (MAPK9) in cell culture exposed to LPS or LPS and the drug compared to the control. We observed that under the LPS and cyclosporine treatment, the expression o/ miR-34a, miR-1275, miR-3188, and miR-382 changed significantly (p < 0.05). We demonstrated a potential relationship between DUSP1 and miR-34a; DUSP4 and miR-34a, miR-382, and miR-3188; MAPK9 and miR-1275, MAP2K7 and mir-200-5p; MAP3K2 and mir-200-5p, which may be the subject of further research in the context of psoriasis.

The impact of wound-healing assay, phorbol myristate acetate (PMA) stimulation and siRNA-mediated FURIN gene silencing on endogenous retroviral ERVW-1 expression level in U87-MG astrocytoma cells.

PURPOSE: Human endogenous retroviruses (HERVs) are ubiquitous genomic sequences. Normally dormant HERVs, undergo reactivation by environmental factors. This deregulation of HERVs' transcriptional equilibrium correlates with medical conditions such as multiple sclerosis (MS). Here we sought to explore whether exposing the U-87 MG astrocytoma cells to traumatic injury deregulates the expression of HERV-W family member ERVW-1 encoding syncytin-1. We also examined the expression of FURIN gene that is crucial in syncytin-1 synthesis. MATERIAL AND METHODS: Scratch assay was used as a model of cells injury in U-87 MG cells. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR), western blot (WB) and migration assay using Boyden chamber were used. Phorbol 12-myristate 13-acetate (PMA) and small interfering RNA (siRNA) were used for cell stimulation and gene expression inhibition, respectively. RESULTS: Results revealed reduced ERVW-1 expression in cells exposed to injury (p â€‹< â€‹0.05) while GFAP gene - a marker of active astrocytes, was upregulated (p â€‹< â€‹0.01). These findings were confirmed by both WB and RT-qPCR. Expression of FURIN gene was not altered after injury, but cell stimulation by PMA strongly increased FURIN expression, simultaneously downregulating ERVW-1 (p â€‹< â€‹0.01). SiRNA-mediated expression inhibition of ERVW-1 and FURIN influenced the mRNA level for SLC1A5 (ASCT2) - primary syncytin-1 receptor, that was significantly lower. FURIN inhibition by siRNA caused strong upregulation of ERVW-1 expression (p â€‹< â€‹0.01). CONCLUSION: Results showed that mechanical impact affects the expression of endogenous retroviruses in U-87 MG astrocytoma cells by scratch assay. Regulation of FURIN, a crucial enzyme in ERVW-1 turnover may support the therapy of some neurological conditions.

High Prevalence of Borrelia burgdorferi Antibodies in Jaworzno, Poland: A Retrospective Study Revealing Endemic Lyme Borreliosis.

BACKGROUND This retrospective study of 704 adult residents of Jaworzno, Poland, aimed to evaluate medical personnel awareness of episodes of Lyme borreliosis and serum antibody levels for Borrelia burgdorferi sensu lato. MATERIAL AND METHODS This study included 704 residents of Jaworzno, Poland, who had no more than 12 months between tick bite and screening. The study consisted of a self-designed questionnaire survey and an analysis of IgG and IgM antibodies against B. burgdorferi sensu lato using an enzyme-linked assay (ELISA) and Western blot analysis, when necessary, to confirm the results. RESULTS A total of 558 residents (79.3%) confirmed having contact with a tick, 84 (11.9%) responded that they did not remember having contact with a tick, and 62 (8.8%) denied having contact with a tick. Regarding IgG, the ELISA showed 183 (25.99%) positive, 440 (62.5%) negative, and 81 (11.5%) equivocal results. Regarding IgM, the ELISA showed 180 (25.57%) positive, 435 (61.79%) negative, and 89 (12.64%) equivocal results. Positive and equivocal results for the IgG and IgM classes using the ELISA test were confirmed in 36 cases (13.64%) for IgG and in 53 cases (19.70%) for IgM using Western blot analysis. CONCLUSIONS The ELISA method obtained similar values for positive, negative, and equivocal results in the serological test. This was reflected in the survey conducted on residents who reported a tick bite and later received a positive result in the ELISA test as well as an approximate time between the bite and removal of the tick.

Evaluation of the Concentration of Selected Elements in the Serum of Patients with Degenerative Stenosis of the Lumbosacral Spine.

In humans, 23 elements have been shown to have biological activity. The purpose of this study was to evaluate the concentrations of iron (Fe), zinc (Zn), sodium (Na), potassium (K), magnesium (Mg), phosphorus (P), and calcium (Ca) in the serum of patients diagnosed with lumbar degenerative stenosis when compared to the concentrations of those elements in the serum of healthy volunteers. The study group consisted of 60 patients who were diagnosed with degenerative stenosis of the lumbosacral spine and who qualified for hemilaminectomy. The control group included 60 healthy volunteers without degenerative spinal stenosis. The clinical specimens studied had sera collected from both groups. The quantitative analysis of the selected elements revealed statistically significant (p < 0.05) lower concentrations of Zn (740 ± 110 µg/L vs. 880 ± 160 µg/L) and Mg (22,091 ± 4256 µg/L vs. 24,100 ± 4210 µg/L) in the serum of the patients from the study group when compared to the controls. By contrast, K (16,230 µg/L ± 1210 µg/L vs. 13,210 µg/L ± 1060 µg/L) and Fe (141.87 µg/L ± 11.22 µg/L vs. 109.1 µg/L ± 26.43 µg/L) levels were significantly higher in the study group compared to the controls (p < 0.05). No statistically significant changes were detected in the concentrations of the assessed micronutrients and macronutrients in both sexes in either the study group, the control group, or those based on body mass index (p > 0.05). In the serum samples from the study group, the strongest correlations were noted between the concentrations. In the study group, we showed a significant relationship between the levels of Fe/Zn (r = 0.41), Fe/Na (r = 0.41), Fe/P (r = 0.55), Zn/P (r = 0.68), Zn/K (r = 0.48), Zn/Ca (r = 0.94), Mg/Ca (r = 0.79), and Na/K (r = 0.67). We showed that only Mg concentration varied statistically significantly with the severity of pain (p < 0.05). These findings suggest that the assessment of Fe, Zn, Mg, and K concentrations can be helpful in predicting the onset of degenerative changes in the spine.

Possibility of Using Surgical Pleth Index in Predicting Postoperative Pain in Patients after Vitrectomy Performed under General Anesthesia.

Adequacy of anesthesia concept (AoA) in the guidance of general anesthesia (GA) is based on entropy, and it also reflects the actual depth of anesthesia and the surgical pleth index (SPI). Therefore, this study aimed to analyze the potential existence of relationships between SPI values at certain stages of the AoA-guided GA for vitreoretinal surgeries (VRS) and the incidence of intolerable postoperative pain perception (IPPP). A total of 175 patients were each assigned to one of five groups. In the first, the VRS procedure was performed under GA without premedication; in the second group, patients received metamizole before GA; in the third, patients received acetaminophen before GA; in the fourth group, patients received Alcaine before GA; and, in the peribulbar block group, the patients received a peribulbar block with a mix of the solutions of lignocaine and bupivacaine. Between the patients declaring mild and statistically significant differences in the IPPP in terms of SPI values before induction (52.3 ± 18.8 vs. 63.9 ± 18.1, p < 0.05) and after emergence from GA (51.1 ± 13 vs. 68.1 ± 8.8; p < 0.001), it was observed that the patients postoperatively correlated with heart rate variations despite the group allocation. The current study proves the feasibility that preoperative SPI values help with predicting IPPP immediately after VRS under AoA guidance and discrimination (between mild diagnoses and IPPP when based on postoperative SPI values) as they correlate with heart rate variations. Specifically, this applies when the countermeasures of IPPP and hemodynamic fluctuations are understood to be of importance in reducing unwelcome adverse events.

The Role of the Gut Microbiome and Microbial Dysbiosis in Common Skin Diseases.

Dermatoses are an increasingly common problem, particularly in developed countries. The causes of this phenomenon include genetic factors and environmental elements. More and more scientific reports suggest that the gut microbiome, more specifically its dysbiosis, also plays an important role in the induction and progression of diseases, including dermatological diseases. The gut microbiome is recognised as the largest endocrine organ, and has a key function in maintaining human homeostasis. In this review, the authors will take a close look at the link between the gut-skin axis and the pathogenesis of dermatoses such as atopic dermatitis, psoriasis, alopecia areata, and acne. The authors will also focus on the role of probiotics in remodelling the microbiome and the alleviation of dermatoses.

Effects of Spherical and Rod-like Gold Nanoparticles on the Reactivity of Human Peripheral Blood Leukocytes.

Gold nanoparticles (GNPs) are widely used in the technological and biomedical industries, which is a major driver of research on these nanoparticles. The main goal of this study was to determine the influence of GNPs (at 20, 100, and 200 µg/mL concentrations) on the reactivity of human peripheral blood leukocytes. Flow cytometry was used to evaluate the respiratory burst activity and pyroptosis in monocytes and granulocytes following incubation with GNPs for 30 and 60 min. Furthermore, the concentration of interleukin-1ß (IL-1ß) in human blood samples was assessed using enzyme-linked immunosorbent assay (ELISA) after their incubation with GNPs for 24 h. Under the conditions tested in the study, the GNPs did not significantly affect the production of reactive oxygen species in the granulocytes and monocytes that were not stimulated using phorbol 12-myristate 13-acetate (PMA) in comparison to the samples exposed to PMA (p < 0.05). Compared to the control sample, the greatest significant increase in the mean fluorescence intensity of the granulocytes occurred in the samples incubated with CGNPs = 100 and 200 µg/mL for tinc = 30 and 60 min (p < 0.05). From our results, we conclude that the physicochemical properties of the nanoparticles, chemical composition, and the type of nanoparticles used in the unit, along with the unit and incubation time, influence the induced toxicity.

The Impacts of Intervertebral Disc Degeneration of the Spine, Alcohol Consumption, Smoking Tobacco Products, and Glycemic Disorders on the Expression Profiles of Neurotrophins-3 and -4.

In the etiology of discogenic pain, attention is paid to the role of neurotrophic factors, which include classic neurotrophins (NTs). This study aimed to assess changes in the concentrations of NT-3 and NT-4 in the intervertebral discs (IVDs) of the lumbosacral (L/S) spine depending on the advancement of degenerative changes, pain severity, habits, and comorbidities. The study group included 113 patients who underwent microdiscectomy due to degenerative IVD disease of the L/S spine. The severity of degenerative IVD changes was assessed using the five-point Pfirrmann scale, and the pain intensity was assessed according to the visual analog scale (VAS). In turn, the control group included 81 participants from whom IVDs of the L/S section of the spine were collected post-mortem during forensic autopsy or organ donation. At the mRNA level, we noted NT-3 overexpression in the test samples compared with the controls (fold change (FC) = 9.12 ± 0.56; p < 0.05), while NT-4 transcriptional activity was decreased in the test samples compared with the controls (FC = 0.33 ± 0.07; p < 0.05). However, at the protein level, the concentrations of NT-3 (134 ± 5.78 pg/mL vs. 6.78 ± 1.17 pg/mL; p < 0.05) and NT-4 (316.77 ± 8.19 pg/mL vs. 76.92 ± 4.82 pg/mL; p < 0.05) were significantly higher in the test samples compared with the control samples. Nevertheless, the concentration of both proteins did not statistically significantly change depending on the advancement of degenerative changes and the pain intensity (p > 0.05). In addition, higher levels of NT-3 and NT-4 were noted in IVD samples from patients who consumed alcohol, smoked tobacco, were overweight/obese, or had comorbid diabetes compared with patients without these risk factors (p < 0.05). Our analysis confirmed that differences in the degenerative process of IVD, energy metabolism, and lifestyle are related to changes in the concentration profiles of NT-3 and NT-4.

Impact of Nutritional Status of Patients with Head and Neck Squamous Cell Carcinoma on the Expression Profile of Ghrelin, Irisin, and Titin.

The goal of this paper was the evaluation of the changes in the expression profile of irisin, ghrelin, and titin in the carcinoma tissue and in the blood of patients with head and neck squamous cell carcinoma (HNSCC), including determining the profile of their expression in relation to patient nutrition. The study included 56 patients with diagnosed squamous cell carcinoma of HNSCC in the T3 and T4 stages of the disease. Healthy control tissue specimens were collected from an area 10 mm outside the histologically negative margin. In turn, the blood and serum from the control group came from healthy volunteers treated for non-oncologic reasons (n = 70). The molecular analysis allowed us to determine the profile of irisin, ghrelin, and titin methylation, evaluate their expression on the level of mRNA (quantitative Reverse Transcription Polymerase Chain Reaction; qRT-PCR) and protein (Enzyme-Linked Immunosorbent Assay Reaction; ELISA) in the carcinoma tissue and the margin of healthy tissue, as well as in serum of patients in the study and control groups. At the start of our observations, a Body Mass Index (BMI) < 18.5 was noted in 42 of the patients, while six months after the treatment a BMI < 18.5 was noted in 29 patients. We also noted a decrease in the expression of irisin, ghrelin, and titin both on the level of mRNA and protein, as well as a potential regulation of their expression via DNA methylation. There is no convincing evidence that the proteins assayed in the present work are specific with regard to HNSSC.

The Adequacy of Anesthesia Guidance for Vitreoretinal Surgeries with Preemptive Paracetamol/Metamizole.

Despite the possibility of postoperative pain occurrence, in some patients, vitreoretinal surgeries (VRSs) require performance of general anesthesia (GA). The administration of intraoperative intravenous rescue opioid analgesics (IROA) during GA constitutes a risk of perioperative adverse events. The Adequacy of Anesthesia (AoA) concept consists of an entropy electroencephalogram to guide the depth of GA and surgical pleth index (SPI) to optimize the titration of IROA. Preemptive analgesia (PA) using cyclooxygenase-3 (COX-3) inhibitors is added to GA to minimize the demand for IROA and reduce postoperative pain. The current analysis evaluated the advantage of PA using COX-3 inhibitors added to GA with AoA-guided administration of IROA on the rate of postoperative pain and hemodynamic stability in patients undergoing VRS. A total of 165 patients undergoing VRS were randomly allocated to receive either GA with AoA-guided IROA administration with intravenous paracetamol/metamizole or with preemptive paracetamol or metamizole. Preemptive paracetamol resulted in a reduction in the IROA requirement; both preemptive metamizole/paracetamol resulted in a reduced rate of postoperative pain as compared to metamizole alone. We recommend using intraoperative AOA-guided IROA administration during VRS to ensure hemodynamic stability alongside PA using both paracetamol/metamizole to reduce postoperative pain.

Efficacy of Continuous-Wave Transscleral Cyclophotocoagulation Post-Pars Plana Vitrectomy in Glaucoma Patients: A Retrospective Study from Poland.

BACKGROUND Glaucoma, a vision-threatening condition, results from optic nerve damage and affects millions of people worldwide. Often asymptomatic, it is hereditary, with risk factors like hypertension, diabetes, and steroid use. Despite its link with intraocular pressure (IOP), not everyone with high IOP develops glaucoma. After pars plana vitrectomy (PPV), patients face increased IOP risks. Traditional treatment includes pharmacotherapy, and, when ineffective, surgical interventions. Continuous-wave transscleral cyclophotocoagulation (CW-TSCPC) is an alternative for refractory glaucoma but can have complications. Our study compares the efficacy and safety of CW-TSCPC after PPV. MATERIAL AND METHODS The study group consisted of 18 patients diagnosed with glaucoma who underwent the CW-TSCP procedure as the first-choice therapy after conservative treatment of glaucoma proved ineffective. The comparison group consisted of 12 patients who underwent the CW-TSCP procedure after conservative drug treatment and in whom surgical treatment of glaucoma had been unsuccessful. All patients had inadequate control of IOP after PPV. RESULTS Study and comparison group patients showed a decrease in IOP during the follow-up, independent of the type of endotamponade used (P<0.05). When the indication for PPV was retinal detachment hemorrhage into the vitreous chamber, a significant decrease in IOP between 0 days and 180 days was only found in the study group (P<0.05). In contrast, when the indication for PPV was the state after uveitis or proliferative diabetic retinopathy, a significant decrease in IOP was found at 180 days in the study and comparison groups (P<0.05). CONCLUSIONS The analysis showed that the CW-TSCPC procedure can be recommended as the first-choice invasive treatment in patients with increased IOP after PPV.

A crossroads between dietary habits, alcohol consumption, and smoking in the clinical course of psoriasis: a narrative review.

Psoriasis is a chronic autoimmune disease that affects 1-3% of the population. The pathomechanism of psoriasis development is complex, but genetic (non-modifiable) factors play a key role. However, the importance of environmental factors and lifestyle choices, such as the diet, alcohol consumption, and smoking, is increasing. The objective of this review was to analyse the influence of dietary habits, alcohol consumption, and smoking on the clinical course of psoriasis. Stress, a poor diet, alcohol abuse, and smoking can trigger psoriasis or cause its exacerbation. Therefore, in addition to the correct selection of therapy, it is extremely important to educate patients about the impact of these factors on the onset and progression of psoriasis. This literature review confirms that a holistic and multidisciplinary approach is required for patients with psoriasis, further emphasizing Hippocrates' thesis, "Let food be thy medicine, and medicine be thy food".

Influence of adalimumab on interleukin 12/23 signalling pathways in human keratinocytes treated with lipopolysaccharide A.

Introduction: The interleukin-12/23 (IL-12/23) signalling pathway plays an important role in the pathogenesis of psoriasis. In addition, even molecularly targeted therapy has been reported to lose adequate response to treatment. Aim: To determine the expression patterns of mRNAs and miRNAs related to IL-12/23 signalling pathways in the human keratinocyte culture exposed to liposaccharide A (LPS) and then adalimumab in comparison with untreated cells. Material and methods: Human, adult, low-Calcium, high-Temperature keratinocyte (HaCaT) cultures were exposed to 1 µg/ml LPS for 8 h, and then adalimumab was added to the cultures at a concentration of 8 µg/ml and incubated for 2, 8, and 24 h. We used mRNA and miRNA microarray, quantitative reverse transcription polymerase chain reaction, and enzyme-linked immunosorbent assay techniques. Results: STAT1, STAT3, STAT5, IL-6, IL-6R, SOCS3, and JAK3 genes differentiated HaCaT cultures with the drug from controls regardless of the time the cells were exposed to the drug. The addition of adalimumab to a culture previously exposed to LPS resulted in silencing of SOCS3 and IL-6 expression compared to the control, while for the other transcripts they were found to be overexpressed compared to the control culture. The assessment indicated the strongest connections between JAK3 and hsa-miR-373-5p (target score 96); SOCS3, STAT5, and hsa-miR-1827 (target score 96). Conclusions: Our study indicates that adalimumab has the strongest modulating effect on mRNA and miRNA expression of JAK/STAT and IL-6-dependent IL-12/23 pathways.

Effect of Glycemic Disorders and Habits on the Concentration of Selected Neurotrophic Factors in Patients with Lumbosacral Intervertebral Disc Degeneration.

BACKGROUND: Unhealthy habits, such as overeating processed and high-calorie foods, alcohol abuse, and smoking, negatively impact human health. It has been suggested that the inflammatory process and the resulting growth of nerve fibers within the intervertebral disc (IVD) fissures is the main reason for the pain accompanying IVD degeneration (IVDD). OBJECTIVES: The aim of this study was to determine whether smoking, alcohol consumption, overweight/obesity, or diabetes comorbidity contribute to the development of IVDD and how the aforementioned factors affect the levels of brain-derived neurotrophic factor (BDNF), glial cell-derived neurotrophic factor (GDNF), and growth associated protein 43 (GAP-43) in the study and control groups (intervertebral discs, IVDs from cadavers, and serum samples from voluntary blood donors). METHODS: The study group comprised 113 patients diagnosed with IVDD who qualified for microdiscectomy. Two control groups (I and II) were used in this study. The first included 81 IVDs obtained from Caucasian human cadavers. Control group II, on the other hand, included serum samples obtained from 113 voluntary blood donors. The expression profiles of BDNF, GDNF, and GAP-43 were determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: Our statistical analysis confirmed that patients who were overweight/obese, smoked tobacco, consumed alcohol, or had diabetes had a higher risk of IVDD (OR > 1). Statistical analysis showed that BDNF, GAP-43, and GDNF concentrations were significantly higher in the IVDs and serum samples obtained from the study group compared to the control group (p < 0.05). In addition, higher levels of BDNF, GDNF, and GAP-43 were noted in IVDD patients who consumed alcohol, smoked tobacco, were overweight/obese, or had comorbid diabetes compared to patients without these risk factors (p < 0.05). CONCLUSION: We showed that changes in energy metabolism, habits, and lifestyle, as well as the degenerative process of IVD in the lumbosacral spine contribute to changing the concentration profile of the analyzed neurotrophic factors.

Impact of Alcohol Consumption, Smoking, and Diet on the Severity of Plaque Psoriasis: A Comprehensive Assessment using Clinical Scales and Quality of Life Measures.

BACKGROUND This study aimed to evaluate the effects of alcohol intake, assessed using the Alcohol Use Disorder Identification Test (AUDIT) questionnaire, on the severity of plaque psoriasis using the Body Surface Area (BSA) and Psoriasis Area and Severity Index (PASI) scales, and quality of life using the Dermatology Life Quality Index (DLQI) questionnaire. MATERIAL AND METHODS The diagnosis of psoriasis was made based on the clinical picture. We enrolled 24 patients with psoriasis vulgaris, and the AUDIT test conducted at the time of follow-up indicated a possible risky/harmful pattern of alcohol consumption or alcohol dependence syndrome among the patients (>8 points). The comparison group consisted of 20 psoriatic patients and AUDIT <8 points. The BSA and PASI scales were used to determine the severity of psoriasis, and the DLQI questionnaire assessed patients' quality of life and how they felt during the week preceding the survey. RESULTS As the amount and frequency of alcohol consumed increased, the exacerbation of lesions measured according to the PASI and BSA scales was significantly higher (P<0.05), and the quality of life decreased (P<0.05). We noted that inadequate and excessive dietary intake of total protein, total fat, and assimilable carbohydrates were associated with statistically significantly higher values of BSA and PASI scores and, thus, more severe psoriatic lesions (P<0.05). CONCLUSIONS An unbalanced diet, alcohol abuse, and smoking negatively affect the course of psoriasis vulgaris, hence the importance of patient education.