Background: Colorectal cancer (CRC) at a current clinical level is still hardly diagnosed, especially with regard to nascent tumors, which are typically asymptotic. Searching for reliable biomarkers of early diagnosis is an extremely essential task. Identification of specific post-translational modifications (PTM) may also significantly improve net benefits and tailor the process of CRC recognition. We examined depleted plasma samples obtained from 41 healthy volunteers and 28 patients with CRC at different stages to conduct comparative proteome-scaled analysis. The main goal of the study was to establish a constellation of protein markers in combination with their PTMs and semi-quantitative ratios that may support and realize the distinction of CRC until the disease has a poor clinical manifestation. Results: Proteomic analysis revealed 119 and 166 proteins for patients in stages I–II and III–IV, correspondingly. Plenty of proteins (44 proteins) reflected conditions of the immune response, lipid metabolism, and response to stress, but only a small portion of them were significant (p < 0.01) for distinguishing stages I–II of CRC. Among them, some cytokines (Clusterin (CLU), C4b-binding protein (C4BP), and CD59 glycoprotein (CD59), etc.) were the most prominent and the lectin pathway was specifically enhanced in patients with CRC. Significant alterations in Inter-alpha-trypsin inhibitor heavy chains (ITIH1, ITIH2, ITIH3, and ITIH4) levels were also observed due to their implication in tumor growth and the malignancy process. Other markers (Alpha-1-acid glycoprotein 2 (ORM2), Alpha-1B-glycoprotein (A1BG), Haptoglobin (HP), and Leucine-rich alpha-2-glycoprotein (LRG1), etc.) were found to create an ambiguous core involved in cancer development but also to exactly promote tumor progression in the early stages. Additionally, we identified post-translational modifications, which according to the literature are associated with the development of colorectal cancer, including kininogen 1 protein (T327-p), alpha-2-HS-glycoprotein (S138-p) and newly identified PTMs, i.e., vitamin D-binding protein (K75-ac and K370-ac) and plasma protease C1 inhibitor (Y294-p), which may also contribute and negatively impact on CRC progression. Conclusions: The contribution of cytokines and proteins of the extracellular matrix is the most significant factor in CRC development in the early stages. This can be concluded since tumor growth is tightly associated with chronic aseptic inflammation and concatenated malignancy related to loss of extracellular matrix stability. Due attention should be paid to Apolipoprotein E (APOE), Apolipoprotein C1 (APOC1), and Apolipoprotein B-100 (APOB) because of their impact on the malfunction of DNA repair and their capability to regulate mTOR and PI3K pathways. The contribution of the observed PTMs is still equivocal, but a significant decrease in the likelihood between modified and native proteins was not detected confidently.
BackgroundThe impact of number of endoscopic enucleation of the prostate techniques (holmium laser enucleation - HoLEP for example) on erectile function have already been investigated. However, the thulium-fiber laser, in this setting remains unstudied. In this study, we compared sexual function outcomes in patients with benign prostatic hyperplasia (BPH) treated with transurethral resection of the prostate (TURP) or thulium-fiber laser enucleation (ThuFLEP).MethodsWe performed a retrospective analysis of patients who underwent transurethral resection and endoscopic enucleation of the prostate for BPH; inclusion criteria was the presence of infravesical obstruction (IPSS > 20, Qmax < 10 mL/s). Erectile function (EF) was assessed using the International Index of Erectile Function (IIEF-5) both prior to endoscopic examination, and six months after.ResultsA total of 469 patients with BPH were included in the study; of these, 211 underwent to ThuFLEP, and 258 TURP. Preoperative IIEF-5 in TURP and ThuFLEP groups were 11.7 (±4.5) and 11.1 (±5.0), respectively (p = 0.17). At six month the IIEF-5 score was unchanged (p = 0.26 and p = 0.08) and comparable in both groups (p = 0.49). However, mean IIEF-5 score shown significant increase of 0.72 in ThuFLEP group, comparing to decrease of 0.24 in TURP patients (p < 0.001).ConclusionsBoth TURP and ThuFLEP are effective modalities in the management of infravesical obstruction due to BPH. At six months follow-up after surgery, both techniques lead to comparable IIEF-5 score. However, our results demonstrated that the ThuFLEP is more likely to preserve the erectile function leading to increase of IIEF-5 at six months in contrast to TURP which lead to slight drop in IIEF-5 score.
Pharmacogenomics is a study of how the genome background is associated with drug resistance and how therapy strategy can be modified for a certain person to achieve benefit. The pharmacogenomics (PGx) testing becomes of great opportunity for physicians to make the proper decision regarding each non-trivial patient that does not respond to therapy. Although pharmacogenomics has become of growing interest to the healthcare market during the past five to ten years the exact mechanisms linking the genetic polymorphisms and observable responses to drug therapy are not always clear. Therefore, the success of PGx testing depends on the physician’s ability to understand the obtained results in a standardized way for each particular patient. The review aims to lead the reader through the general conception of PGx and related issues of PGx testing efficiency, personal data security, and health safety at a current clinical level.
Nanoribbon chips, based on “silicon-on-insulator” structures (SOI-NR chips), have been fabricated. These SOI-NR chips, whose surface was sensitized with covalently immobilized oligonucleotide molecular probes (oDNA probes), have been employed for the nanoribbon biosensor-based detection of a circular ribonucleic acid (circRNA) molecular marker of glioma in humans. The nucleotide sequence of the oDNA probes was complimentary to the sequence of the target oDNA. The latter represents a synthetic analogue of a glioma marker—NFIX circular RNA. In this way, the detection of target oDNA molecules in a pure buffer has been performed. The lowest concentration of the target biomolecules, detectable in our experiments, was of the order of ~10−17 M. The SOI-NR sensor chips proposed herein have allowed us to reveal an elevated level of the NFIX circular RNA in the blood of a glioma patient.
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