Autophagy is a highly conserved mechanism of self-digestion that removes damaged organelles and proteins from cells. Depending on the way the protein is delivered to the lysosome, four basic types of autophagy can be distinguished: macroautophagy, selective autophagy, chaperone-mediated autophagy and microautophagy. Macroautophagy involves formation of autophagosomes and is controlled by specific autophagy-related genes. The steps in macroautophagy are initiation, phagophore elongation, autophagosome maturation, autophagosome fusion with the lysosome, and proteolytic degradation of the contents. Selective autophagy is macroautophagy of a specific cellular component. This work focuses on mitophagy (selective autophagy of abnormal and damaged mitochondria), in which the main participating protein is PINK1 (phosphatase and tensin homolog-induced putative kinase 1). In chaperone-mediated autophagy, the substrate is bound to a heat shock protein 70 chaperone before it is delivered to the lysosome. The least characterized type of autophagy is microautophagy, which is the degradation of very small molecules without participation of an autophagosome. Autophagy can promote or inhibit tumor development, depending on the severity of the disease, the type of cancer, and the age of the patient. This paper describes the molecular basis of the different types of autophagy and their importance in cancer pathogenesis.

Endometrial cancer develops as a result of abnormal cell growth associated with uncontrolled cell proliferation, excessive activation of signaling pathways and miRNA activity. The aim of this study was to determine the expression profile of genes associated with cell proliferation and to assess which miRNAs can participate in the regulation of their expression. The study enrolled 40 patients with endometrial cancer and 10 patients without neoplastic changes. The expression profile of genes associated with cell proliferation and the expression profile of miRNAs were assessed using microarrays. RT-qPCR was performed to validate mRNA microarray results. The mirTAR tool was used to identify miRNAs that regulate the activity of genes associated with cell proliferation. Decreased expression of IGF1 and MYLK, as well as SOD2 overexpression, were observed in endometrial cancer using both mRNA microarrays and RT-qPCR. Microarray analysis showed low levels of NES and PRKCA, but this was only partially validated using RT-qPCR. Reduced activity of MYLK may be caused by increased miR-200c, miR-155 and miR-200b expression. Cell proliferation is disturbed in endometrial cancer, which may be associated with an overexpression of miR-200a, miR-200c, and miR-155, making it a potential diagnostic marker.

Objective The aim of this study was to evaluate the influence of adalimumab on expression profile of genes associated with the histaminergic system in Normal Human Dermal Fibroblast (NHDF) cells stimulated with 8.00 μg/ml of adalimumab and the identification of miRNAs regulating these genes' expression. Methods NHDFs were cultured with or without the presence of adalimumab for 2, 8, and 24 hours. The expression profile of genes and miRNA were determined with the use of microarray technology. Results Among 22283 ID mRNA, 65 are associated with the histaminergic system. It can be observed that 15 mRNAs differentiate NHDFs cultures with adalimumab form control. The analysis of miRNAs showed that, among 1105 ID miRNA, 20 miRNAs are differentiating in cells treated with adalimumab for 2 hours, 9 miRNA after 8 hours, and only 3 miRNAs after 24 hours. Conclusion It was also determined that miRNAs play certain role in the regulation of the expression of genes associated with the histaminergic system. The results of this study confirmed the possibility of using both genes associated with this system as well as miRNAs regulating their expression, as complementary molecular markers of sensitivity to the adalimumab treatment.

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Background and Objectives: Although vitreoretinal surgery (VRS) is most commonly performed under regional anaesthesia (RA), in patients who might be unable to cooperate during prolonged procedures, general anaesthesia (GA) with intraprocedural use of opioid analgesics (OA) might be worth considering. It seems that the surgical pleth index (SPI) can be used to optimise the intraprocedural titration of OA, which improves haemodynamic stability. Preventive analgesia (PA) is combined with GA to minimise intraprocedural OA administration. Materials and Methods: We evaluated the benefit of PA combined with GA using SPI-guided fentanyl (FNT) administration on the incidences of PIPP (postprocedural intolerable pain perception) and haemodynamic instability in patients undergoing VRS (p < 0.05). We randomly assigned 176 patients undergoing VRS to receive GA with SPI-guided FNT administration alone (GA group) or with preventive topical 2% proparacaine (topical anaesthesia (TA) group), a preprocedural peribulbar block (PBB) using 0.5% bupivacaine with 2% lidocaine (PBB group), or a preprocedural intravenous infusion of 1.0 g of metamizole (M group) or 1.0 g of paracetamol (P group). Results: Preventive PBB reduced the intraprocedural FNT requirement without influencing periprocedural outcomes (p < 0.05). Intraprocedural SPI-guided FNT administration during GA resulted in PIPP in 13.5% of patients undergoing VRS and blunted the periprocedural effects of preventive intravenous and regional analgesia with respect to PIPP and haemodynamic instability. Conclusions: SPI-guided FNT administration during GA eliminated the benefits of preventive analgesia in the PBB, TA, M, and P groups following VRS.

Lucilia sericata bottle fly worms can be used to heal infected, chronic, or necrotic wounds, including those associated with ulceration and diabetic foot.The study aimed to evaluate changes in the microflora in patients treated with L sericata larvae due to leg ulcers and diabetic foot. One hundred twenty-nine patients diagnosed with lower limb ulceration and diabetic foot were enrolled in the study, of which 80 of them met the eligibility criteria for maggot debridement therapy (MDT). On the contrary, 49 unqualified patients were offered ozone therapy (22 with leg ulcers; 27 with diabetic foot). In each of these patients, a microbiological swab was performed before and after the start of therapy. The group of 80 patients was further divided into four equal groups in terms of the treated area (lower leg vs foot) and the number of larvae/cm 2 (5 vs 10). Twenty-three particular species of bacteria in the infected wound were studied microbiologically in terms of presence/absence within the wound environment before and after treatment of patients with diabetic foot and lower limb ulceration. It was noted that there was a more intensive bacterial accumulation in the feet of patients compared to legs; furthermore, this applies to almost all analysed species. Diabetes status is also a clinical factor that generates a lower chance of bacterial appearance in the wound environment. Densification of MDT larvae per wound area unit also reduced the chance of the presence of Corynebacterium species, Enterobacteriaceae, Pseudomonas aeruginosa, Staphylococcus aureus MSSA, and Streptococcus coagulase negativa; however, it increased the likelihood of occurrence for Proteus mirabilis and the Proteus species. A microbiological analysis in this non-reference study shows the efficacy of larval therapy for leg and foot ulcers. Rearrangement of the microflora within the wound has been reported as a result of the therapy.

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.

Departmental sources Background: Pars plana vitrectomy (PPV) is used to treat retinal conditions, including retinal detachment, and involves removal of the vitreous gel from the eye. Complications following PPV include raised intraocular pressure (IOP). This retrospective study aimed to compare methods of endotamponade used during 23-gauge PPV and the risk of raised IOP during 24-month follow-up at a single center. Material/Methods: The study included 196 patients (age, 15-86 years; mean, 63.5 years) (196 eyeballs). There were 93 patients (47.45%) with a preoperative history of type 2 diabetes mellitus and 14 patients (7.14%) with a history of myopia. IOP was measured with Goldmann applanation tonometry at one-, three-, six-, 12-, and 24-month follow-up. The outcome was compared following endotamponade with silicone oil, sulfur hexafluoride (SF6), and balanced salt solution (BSS). Results: Mean IOP at one-month follow-up was 17.2 mmHg (±3.61 mmHg; range, 9-45 mmHg), and at 24-month follow-up was 17.3 mmHg (±3.23 mmHg; range, 7-30 mmHg). IOP following PPV was significantly associated with the indication for PPV (P=0.023), and the type of endotamponade used (P=0.049). In patients with silicone oil endotamponade, the risk of IOP at 24 months was increased by 2.3 times compared with SF6 or BSS endotamponade. Patients with SF6 endotamponade had a risk of IOP that was 3.3 times lower than for silicone oil tamponade or BSS tamponade. Conclusions: Silicone oil endotamponade in PPV was associated with an increased risk of IOP at 24-month follow-up.