The characterization of tumor necrosis factor alpha (TNF-α), its role in cancerogenesis and cardiovascular system diseases and possibilities of using this cytokine as a molecular marker

The inflammatory process is directly associated with secretion of cytokines, e.g. tumor necrosis factor alpha (TNF-α). This molecule is one of the 22 proteins which belong to TNF family and is secreted mainly by: macrophages, monocytes, T lymphocyte and mast cells. The biological effects of TNF-α is possible through binding this cytokine to specific receptors - TNFR1 and TNFR2. The large number of reports provides that this cytokine plays extremely important role in cancers and cardiovascular disease - two groups of inflammatory diseases. Unfortunately, these diseases are the main cause of death in spite of advances in medicine and increasing public awareness of prevention. It is believed that better understanding both molecular potential of this cytokine and the impact in cancerogenesis and others inflammatory diseases may cause using TNF-α as a molecular marker in these diseases and will make it possible to observe the effects of anti-inflammatory therapy. It will be able to cause a drop in the incidence of these diseases and better monitoring of them

Comprehensive molecular and clinical analysis of adalimumab and etanercept therapeutic potentialin patients with psoriatic arthritis

Introduction: Adalimumab and etanercept are drugs used in anti-TNF therapy in patients with psoriasis and psoriatic arthritis. Despite the molecular targeting of these drugs, the loss of pharmacological response to treatment is observed in patients. The development of personalized medicine makes it possible to use not only clinical parameters of disease severity, but also molecular marker systems. Aim: The aim of the study was to evaluate the changes in TNF-α, TNFR1, and TNFR2 expression in relation to parameters of disease severity (PASI, BSA, DAS28) in patients treated with adalimumab and etanercept. We have attempted to determine whether changes in the TNF-α, TNFR1, and TNFR2 expression profile may be a useful molecular marker of the therapeutic potential of anti-TNF drugs. Material and methods: The study group consisted of 3 patients initially treated with adalimumab, followed by etanercept. The control group included 20 healthy volunteers. The expression profile of TNFR1 and TNFR2 was determined at the mRNA level, while TNF-α expression was evaluated at the transcriptome and proteome levels using the RT-qPCR method (transcriptional activity assay) and MALDI-TOF MS (protein level assessment). Results: Depending on the drug, different expression profiles of the studied cytokines are observed. Conclusions: The obtained data indicate that TNF-α, TNFR1, and TNFR2 may be useful markers of the efficacy of anti-TNF therapy, thus complementing clinical parameters

Analysis of molecular and clinical parameters of 4-year adalimumab therapy in psoriatic patients

Introdcution: Through interaction with receptors TNFR1 and TNFR2, TNF-α activates a signal path, which exacerbates an inflammatory process, constituting an inseparable element of psoriasis. Aim: To evaluate changes in the expression of TNF-α, TNFR1, TNFR2 during the 4-year-long adalimumab therapy in psoriatic patients, searching for the correlation between molecular and clinical markers. In addition, the role of miRNAs was analysed. Material and methods: Whole blood and serum samples of psoriatic patients treated with adalimumab constituted material for the study. Changes in the expression of TNF-α and its receptors were evaluated with the use of the RTqPCR method and MALDI ToF mass spectroscopy, PASI, BSA, DAS28 indexes were used for the clinical analysis of the patients, while the role of miRNA molecules was determined basing on microrna.org database. Results: Different TNF-α expression patterns were determined in patients with observed resistance to the medicine. We found that there is a correlation between the molecular markers of an inflammatory process and the clinical indexes. The bioinformatic analysis indicates the potential role of miRNAs in the regulation of expression of the analysed genes. Changes in the profile of TNF-α during adalimumab therapy are significantly determined by the individual variability and susceptibility to the biological medicine or its loss. Conclusions: TNF-α seems to be a useful marker to evaluate the efficacy of therapy and occurring resistance to the medicine. A complex mechanism for the regulation of the analysed gene expression was underlined, which involved the potential role of miRNAs

Risk Assessment of the Increased Occurrence of Congenital Cardiac and Non-Cardiac Defects in Fetuses with a Normal Karyotype after Assisted Fertilization in Comparison to Natural Fertilization Based on Ultrasound Diagnostics

The goal of the study was to assess changes in parameters based on ultrasound examinations—these were Crown Rump Length (CRL), Nuchal Translucency (NT), Fetal Heart Rate (FHR), and Pulsatility Index for Ductus Venosus (DV-PI)—in the first trimester of pregnancy in women in which there was a natural initiation of the pregnancy due to spontaneous ovulation, women in which the pregnancy was initiated as a result of stimulated ovulation, as well as in the group in which pregnancy was achieved through the use of In-Vitro Fertilization (IVF)-assisted reproduction. A total of 1581 women became pregnant without the use of assisted reproduction methods. Out of 283 pregnancies, in 178 patients, induced ovulation was utilized. Next, 137 women had sexual intercourse and became pregnant; 41 of them became pregnant through Intrauterine Insemination (IUI) as a result of Artificial Insemination by Husband (AIH), and 13 became pregnant after Artificial Insemination by Donor (AID). The third group consisted of 105 women subjected to Controlled Ovarian Hyperstimulation (COH). In this group of pregnant women, 53 pregnancies were resultant of Intracytoplasmic Sperm Injection (ICSI), and 52 pregnancies were the result of Intracytoplasmic Morphologically selected Sperm Injection (IMSI). The obtained results did not indicate that the chosen method of fertilization or the chosen ovulation method had a statistically significant effect on the development risk of congenital heart or non-heart defects in the fetus

Expression Pattern of Leptin and Its Receptors in Endometrioid Endometrial Cancer

The identification of novel molecular markers and the development of cancer treatment strategies are very important as cancer incidence is still very high. Obesity can contribute to cancer progression, including endometrial cancer. Adipocytes secrete leptin, which, when at a high level, is associated with an increased risk of cancer. The aim of this study was to determine the expression profile of leptin-related genes in the endometrial tissue samples and whole blood of patients. The study material included tissue samples and whole blood collected from 30 patients with endometrial cancer and 30 without cancer. Microarrays were used to assess the expression profile of leptin-related genes. Then, the expression of leptin (LEP), leptin receptor (LEPR), leptin receptor overlapping transcript (LEPROT), and leptin receptor overlapping transcript-like 1 (LEPROTL1) was determined by the Real-Time Quantitative Reverse Transcription Reaction (RT-qPCR). The serum leptin concentration was evaluated using Enzyme-linked immunosorbent assay (ELISA). Leptin and its receptors were overexpressed both at the mRNA and protein levels. Furthermore, there were strong positive correlations between leptin levels and patient Body Mass Index (BMI). Elevated levels of leptin and its receptors may potentially contribute to the progression of endometrial cancer. These observations may be useful in designing endometrial cancer treatment strategies

Współwystępowanie łuszczycy z układowymi chorobami metabolicznymi – problem interdyscyplinarny

INTRODUCTION: The aim of this study was to assess how often psoriasis co-occurs with diabetes, hypertension, and metabolic syndrome. The intention of the authors is to draw the attention of general practitioners, to the complex clinical picture of psoriasis, the implications of internist diseases, and thus the need to provide patients with interdisciplinary care. MATERIAL AND METHODS: A survey on the prevalence of metabolic systemic comorbidities with psoriasis was performed on a group of 32 patients diagnosed with common psoriasis (20 men and 12 women). The characteristics of the study group are as follows (mean ± standard deviation): age 53.9 ± 10.4 years, height 169.9 ± 1.5 cm, body weight 88.8 ± 21.5 kg, BMI 30.65 ± 6.18, waist circumference 108.34 ± 17.14 cm. RESULTS: Of the 32 patients with psoriasis, syndrome X and hypertension were found in 15 patients, diabetes in 7, diabetes and metabolic syndrome in 9 patients, hypertension and metabolic syndrome in 9, hypertension and diabetes in 6 and concomitant concurrent diabetes, metabolic syndrome and hypertension in 14 patients. CONCLUSIONS: Patients with psoriasis should be given interdisciplinary, comprehensive specialist care due to the increased risk of comorbidity of systemic diseases. The coexistence of systemic diseases in patients with psoriasis, exacerbates existing inflammation. The general practitioner plays a key role in the entire diagnostic and therapeutic process of psoriasis, therefore better understanding of the complex pathomechanisms underlying this dermatosis is necessary, which is the key to effective and safe pharmacotherapy.WSTĘP: Celem niniejszej pracy była ocena częstości współwystępowania łuszczycy z cukrzycą, nadciśnieniem tętniczym i zespołem metabolicznym. Zamiarem autorów jest zwrócenie uwagi lekarzy rodzinnych na złożony obraz kliniczny łuszczycy, implikacje ze schorzeniami internistycznymi, a tym samym konieczność objęcia chorych opieką interdyscyplinarną. MATERIAŁ I METODY: Ankietę dotyczącą częstości występowania metabolicznych układowych chorób współistniejących z łuszczycą przeprowadzono w grupie 32 pacjentów z rozpoznaną łuszczycą zwykłą (20 mężczyzn i 12 kobiet). Charakterystyka grupy badanej przedstawia się następująco (średnia ± odchylenie standardowe): wiek 53,9 ± 10,4 roku, wzrost 169,9 ± 1,5 cm, masa ciała 88,8 ± 21,5 kg, BMI 30,65 ± 6,18, obwód talii 108,34 ± 17,14 cm. WYNIKI: Spośród 32 pacjentów z łuszczycą zespół X i nadciśnienie stwierdzono u 15, cukrzycę u 7, cukrzycę i zespół metaboliczny u 9, nadciśnienie tętnicze i zespół metaboliczny u 9, nadciśnienie tętnicze i cukrzycę u 6, natomiast współwystępowanie cukrzycy, zespołu metabolicznego i nadciśnienia tętniczego u 14 chorych. WNIOSKI: Pacjenci z łuszczycą powinni zostać objęci interdyscyplinarną, kompleksową opieką specjalistyczną ze względu na podwyższone ryzyko współwystępowania schorzeń układowych. Współwystępowanie w tej grupie internistycznych chorób ogólnoustrojowych nasila istniejący stan zapalny. Lekarz pierwszego kontaktu odgrywa główną rolę w całym procesie diagnostyczno-terapeutycznym łuszczycy. Niezbędne jest lepsze zrozumienie złożonych patomechanizmów leżących u podstaw tej dermatozy, co stanowi klucz do skutecznej i bezpiecznej farmakoterapii

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

Expression Profile of mRNAs and miRNAs Related to the Oxidative-Stress Phenomenon in the Ishikawa Cell Line Treated Either Cisplatin or Salinomycin

The oxidative stress phenomenon is a result of anticancer therapy. The aim of this study was the assessment of gene expression profile changes, and to determine the miRNAs regulating genes’ transcriptional activity in an Ishikawa endometrial cancer culture exposed to cisplatin or salinomycin, compared to a control culture. The molecular analysis comprised the microarray technique (mRNAs and micro RNA (miRNA), the real-time quantitative reverse transcription reaction (RTqPCR), enzyme-linked immunosorbent assay (ELISA) reactions, and Western blot. NR4A2, MAP3K8, ICAM1, IL21, CXCL8, CCL7, and SLC7A11 were statistically significantly differentiated depending not only on time, but also on the drug used in the experiment. The conducted assessment indicated that the strongest links were between NR4A2 and hsa-miR-30a-5p and has-miR-302e, MAP3K8 and hsa-miR-144-3p, CXCL8 and hsa-miR-140-3p, and SLC7A11 and hsa-miR-144-3p. The obtained results suggest that four mRNAs—NR4A2, MAP3K8, CXCL8 and SLC7A11—and four miRNAs—hsa-miR-30a-5p, hsa-miR-302e, hsa-miR-144-3p and hsa-miR-140-3—changed their expressions regardless of the chemotherapeutic agent used, which suggests the possibility of their use in monitoring the severity of oxidative stress in endometrial cancer. However, considering the results at both the mRNA and the protein level, it is most likely that the expressions of NR4A2, MAP3K8, CXCL8 and SLC7A11 are regulated by miRNA molecules as well as other epigenetic mechanisms