Good cop-bad cop: different roles of hsa-miR-93-5p in colorectal cancer

Colorectal cancer (CRC) is a heterogeneous disease that ranks third and second globally in terms of incidence and mortality rates, respectively. Five-year survival of patients with CRC is approximately 90% if diagnosed in the early stages, and only 13% if the advance disease is present. About 25% of patients already have CRC metastases (mCRC) with the primary CRC diagnosis, while half of the patients will develop metastases with further disease progression. The most common organ in which CRC metastasizes is the liver (colorectal cancer liver metastasis, CRLM). Almost half of CRC patients will die due to complications caused by the presence of metastases, so it is extremely important to discover new therapeutic approaches, as well as prognostic and predictive biomarkers, in order to reduce such a high mortality rate. In the era of personalized medicine, various treatment modalities are available to CRC and mCRC patients, including resective surgery, systemic chemotherapy, and novel targeted biologics, which significantly improved the outcome of CRC patients. The main goal of neoadjuvant systemic chemotherapy is to render currently unresectable disease amenable to resection. The standard cytotoxic drugs used in systemic chemotherapy for the treatment of CRC are: 5-fluorouracil (5-FU), oxaliplatin, and irinotecan applied as single agents or combined. It has been shown that the combination of systemic chemotherapy with targeted biological agents (e.g., bevacizumab which targets vascular endothelial growth factor) leads to a better therapy response compared to the use of systemic chemotherapy alone. MicroRNA (miRNA) molecules belong to a large class of small regulatory non-coding single-stranded RNA molecules that exert negative post-transcriptional regulation of gene expression. MiRNAs are involved in the regulation of fundamental cellular processes such as cell proliferation, differentiation and death, thus these molecules have been proposed as one of the regulators of oncogenesis, considering that they can have an oncogenic or tumor-suppressive role, which can be tumor-specific. The miRNA expression pattern is consistently and reproducibly altered in CRC compared with normal intestinal mucosa, and this expression pattern changes during the progression from normal colon, through adenoma to colorectal cancer. Not surprisingly, microRNAs have been implicated in the CRC growth, progression, metastasis, and response to therapy. MiRNAs have also been studied as potential diagnostic, prognostic and predictive biomarkers, and therapeutic agents or targets. To date, a small number of molecular biomarkers have been identified that can predict patient's response to therapy and thus help doctors in decision making to select the right therapy for a given patient. Identification of new validated predictive and prognostic biomarkers will be necessary to improve the quality of life and outcome of CRC patients. Hsa-miR-93-5p, together with hsa-miR-106b and hsa-miR-25, belongs to the miR-106b-25 cluster located on the 515 bp long region of chromosome 7q22, within intron 13 of the MCM7 gene. Interestingly, hsa-miR-93-5p has been reported to have oncogenic and tumor-suppressive roles in different tumor types. This systematic review aims to present the current knowledge on the role of hsa-miR-93-5p in the processes related to colorectal carcinogenesis, metastasis, and response to chemotherapy in patients with primary and metastatic colorectal cancer. Also, the role of hsa-miR-93-5p as a potential prognostic and predictive biomarker is described

Surface chemistry of "boron" doped carbon quantum dots

Carbon quantum dots (CQDs), are a novel class of carbon nanomaterials that exhibit outstanding physical, chemical, and optical characteristics in addition to strong light absorption. By substituting some of the carbon atoms in CQDs for heteroatoms like N, B, P, and S, it is possible to modify the surface chemistry and electronic properties of the structures, boosting their catalytic activity. Adding B dopant to CQDs changes its surface chemistry and morphology, opening up a wide range of potential uses. The presented study illustrates a quick and environmentally friendly method for producing B-CQDs through microwave-assisted method. According to TEM characterization, the generated B-CQDs had a spherical form, an average diameter of 12 nm, and were negatively charged particles with good water dispersibility and no discernible aggregation. The thorough surface chemistry characterization revealed the presence of B-O and B-C bonds, as well as oxygen-containing surface functional groups in the form of hydroxyl, carbonyl, and carboxyl groups. Additionally, using an RB organic dye as a model molecule, the sonocatalytic, photocatalytic, and synergistic effects of the two processes were investigated

Genetic analysis of SMAD4 C-terminal domain in patients with microsatellite stable early- age onset colorectal cancer

SMAD4 protein loss is a relatively common feature of sporadic colorectal cancers (CRC), and it was observed to be even more frequent in early-age onset CRC patients and microsatellite stable (MSS) tumors. Pathogenic variants in the SMAD4 gene are usually missense or nonsense mutations, and they are more frequent in the C-terminal domain. The aim of this study was to perform genetic analysis of SMAD4 C-terminal domain of MSS early-age onset CRC patients. This pilot study was conducted with a purpose of investigating if such genetic screening strategy would be useful for diagnostic purposes in this specific subgroup of CRC patients.On June 24 and 25, 2021, Fight Colorectal Cancer (Fight CRC) and Dr. José Perea from Fundación Jiménez Díaz University Hospital in Madrid, Spain, virtually co-hosted the third annual early-age onset colorectal cancer (EAO CRC) international symposium, Rally on Research: EAO CR

Promene linearnih i nelinearnih mera nizova RR i QT intervala posle uzimanja piva

BACKGROUND: /Aim. There are only several studies on the acute effect of alcoholic drinks intake on heart rhythm and this phenomenon is still not well understood. We wanted to examine whether linear and nonlinear measures of RR interval and QT interval series could quantify the effect of beer in healthy subjects. Methods. Eighteen young volunteers drank 500 mL of beer (21 g of ethanol). Electrocardiogram (ECG) recordings were taken in supine position: 20 minutes before (relaxation) and 60 minutes after drink intake. The RR interval series and the QT interval series were extracted from ECG and we calculated short-term (α1) and long-term (α2) scaling exponents and sample entropy (SampEn) for both series; low frequency (LF) and high frequency (HF) spectral components from RR interval series and QT variability (QTV). Blood pressure was measured every 10 minutes. Results. It was shown that beer induced changes in variability and correlation properties of these series. Immediate effect of beer intake was detected as a transient increase in the QT variability, heart rate and blood pressure. Delayed effects of beer were shortening of the RR and QT intervals and reduction of the HF spectral component. Beer intake also increased short-term scaling exponent (α1) of the RR time series and long-term scaling exponent (α2) of the QT time series. Conclusion. Our results suggest that acute effects of beer are reduced parasympathetic control of the heart and changed dynamic complexity of the ventricular repolarization.Uvod/Cilj. Akutni efekat uzimanja alkoholnih pića na kardiovaskularne ritmove je fenomen koji još uvek nije dovoljno razjašnjen i u literaturi postoji svega nekoliko radova na tu temu. Cilj rada je bio da se ispita da li se linearnim i nelinearnim merama nizova RR i QT intervala može kvantifikovati akutni efekat male količine piva kod zdravih osoba. Metode. Osamnaest mladih zdravih muškaraca je pilo po 500 mL piva (21 g etanola). Elektrokardiogram (EKG) je beležen u ležećem položaju: 20 minuta pre (u relaksaciji) i 60 minuta neposredno posle uzimanja pića. Iz digitalizovanog zapisa EKG-a izdvojeni su nizovi RR i QT intervala. Iz oba niza smo izračunali kratkodometni (α1) i dugo-dometni skalirajući eksponent (α2), kao i entropiju uzorka (SampEn). Iz nizova RR intervala određene su spektralne komponente niskofrekventnih (LF) i visokofrekventnih (HF) opsega, a iz nizova QT intervala varijabilnost QT intervala (QTV). Krvni pritisak je bio meren svakih 10 minuta. Rezultati. Pokazali smo da pivo menja varijabilnost i korelacione osobine ovih nizova. Neposredni efekat uzimanja piva ogleda se u prolaznim povećanjima QT varijabilnosti, srčane frekvence i krvnog pritiska, a produženi u skraćenju dužine RR i QT intervala i smanjenju spektralne komponente HF. Uzimanje piva je takođe dovelo do porasta kratkodometnog skalirajućeg eksponenta (α1) RR niza i dugodometnog skalirajućeg eksponenta (α2) QT niza. Zaključak. Akutni efekat uzimanja piva je redukovana parasimpatička kontrola srca i izmenjena kompleksnost dinamike ventrikularne repolarizacije

Effects of Chemotherapy for Metastatic Colorectal Cancer on the TGF-beta Signaling and Related miRNAs hsa-miR-17-5p, hsa-miR-21-5p and hsa-miR-93-5p

Metastatic colorectal cancer (mCRC) patients are treated with standard chemotherapeutic drugs in the form of FOLFOX and FOLFIRI regimens. There are no reliable markers that could predict response to chemotherapy for mCRC. TGF-beta signaling which interacts with microRNA (miRNA) network has important roles in tumor progression and chemotherapy resistance, thus the interplay between TGF-beta signaling and miRNAs could be crucial for treatment response. The aim of this study was to analyze the effect of chemotherapy for mCRC on TGF-beta signaling and related miRNAs. Hsa-miR-17-5p, hsa-miR-21-5p and hsa-miR-93-5p were selected out of 316 miRNAs with multiple targets within the TGF-beta signaling by in silico analysis. SW620 cells were treated with chemotherapeutic drugs for mCRC for 1, 3 and 6 days and expression of selected miRNAs, PAI-1, CDH1 and VIM was measured. Expression of TGF-beta signaling-related hsa-miR-17-5p, hsa-miR-21-5p and hsa-miR-93-5p was time-dependently altered in SW620 cells treated with chemotherapeutics for mCRC. The expression of hsa-miR-93-5p remained downregulated after 6 days under combined treatments FOX and FIRI as well as the hsa-miR-17-5p expression under FIRI. Chemotherapy regimens for mCRC increased expression of a major TGF-beta signaling target gene PAI-1, independently of the selected miRNAs expression. These treatments also increased the expression of epithelial-mesenchymal transition (EMT) markers CDH1 and VIM on day 3 resulting in decrease of mesenchymal-like characteristics. However, their expression returned close to basal level on day 6. In conclusion, after initial response to chemotherapeutic drugs SW620 cells start to return close to the basal mesenchymal state while the long-term downregulated expression pattern of hsa-miR-93-5p and hsa-miR-17-5p makes them candidates worth testing as biomarkers for monitoring combined chemotherapeutic treatments therapy response in mCRC patients