Circulating microRNAs are a potential molecular link between nutrition and colorectal cancer risk in Lynch Syndrome

Lynch syndrome is an inherited cancer-predisposing syndrome where occur mutations in mismatch repair genes. Colorectal cancer is a common form of cancer within Lynch syndrome carriers. The inherited gene mutation predisposes to the development of colorectal cancer, but diet, especially red meat, fiber, and calcium intake, is known to significantly impact cancer development. Currently, there is limited information on what kind of molecular mechanisms mediate the effect of nutrition on colorectal cancer risk within Lynch syndrome carriers. Recent studies have indicated the importance of circulating non-coding RNAs, like microRNAs, in cancer development. Circulating microRNAs are small approximately 20 nucleotide long molecules in the bloodstream that regulate several biological processes. Circulating microRNA expression patterns change in connection with cancer. This thesis aimed to study whether red meat, fiber, and calcium daily intake are associated with circulating microRNA expression levels of Lynch syndrome carriers. The associations between nutrient intake and circulating microRNA expression levels were studied using the Spearman rank correlation coefficient and multiple linear regression analysis. The statistical tests revealed significant associations between these variables where hsa-miR-3613-5p was specifically associated with red meat intake and hsa-miR-144-5p with fiber intake. The possible function of hsa-miR-3613-5p and hsa-miR-144-5p in colorectal cancer was studied by transfecting appropriate microRNA mimics in patient-derived colorectal cancer organoids and by performing cell viability and apoptosis assays to the transfected cells. Hsa-miR-144-5p reduced the viability of colorectal cancer cells and in addition induced apoptosis in these cells. Hsa-miR-3613-5p had no clear effect on the viability of the studied cancer cells. The study suggests nutrition has an impact on circulating microRNA expression levels. In addition, these microRNAs associated with diet may enhance or suppress colorectal cancer cell growth

LANTIONPOHJA TUTUKSI – Opas fysioterapeuttiopiskelijoille lantionpohjan lihasten tutkimiseen ja harjoittamiseen

Lantionpohjan toimintahäiriöt vaikuttavat elämänlaatuun heikentävästi. Toimintahäiriöitä ovat virtsaamiseen, ulostamiseen ja seksuaalitoimintoihin liittyvät häiriöt, laskeumat ja lantion sekä selän kiputilat. Toimintahäiriöille altistavat esimerkiksi raskaus, synnytys ja ikääntyminen. Naiset ovat anatomisten rakenteidensa vuoksi alttiimpia lantionpohjan toiminnanhäiriöille, mutta myös miehillä ilmenee lantionpohjan toimintahäiriöitä. Lantionpohjan lihasten tunnistamis-, rentoutus- ja lihasvoimaharjoittelulla voidaan ehkäistä ja hoitaa näitä toimintahäiriöitä tuloksekkaasti. Opinnäytetyön tarkoitus oli lisätä fysioterapeuttiopiskelijoiden tietoisuutta lantionpohjan fysioterapiasta. Tavoitteena oli tuottaa teoriatietoon perustuva sähköinen opas Karelia-ammattikorkeakoulun Fysiotikan käyttöön. Opasta on mahdollista hyödyntää fysioterapeuttiopinnoissa. Opinnäytetyön prosessiin kuului tietoperustan kokoaminen lantionpohjan fysioterapiasta ja sen pohjalta opas koottiin. Oppaasta kerättiin palautetta Karelia-ammattikorkeakoulun fysioterapeuttiopiskelijoilta, -opettajilta ja työelämässä olevilta fysioterapeuteilta. Jatkokehitysideana voisi tuottaa oppaan neurologisten asiakkaiden lantionpohjan fysioterapiasta.Pelvic floor dysfunctions affect the quality of life negatively. Pelvic floor dysfunctions comprise urinary and faecal incontinence, sexual dysfunctions, pelvic organ prolapses, and pelvic- and back pain disorders. The main risk factors for pelvic floor dysfunctions are pregnancies, deliveries and aging. Although women are more susceptible to pelvic floor dysfunctions due to female anatomical structures, also men have pelvic floor dysfunctions. Pelvic floor muscle recognition, relaxation, and muscle strength training can effectively prevent and treat these dysfunctions. The purpose of this thesis was to increase the knowledge to physiotherapy students on pelvic floor physiotherapy. The aim of this theory-based bachelor’s thesis was to pro- duce electronic educational material on pelvic floor physiotherapy for Fysiotikka and the students of Karelia University of Applied Science. This educational material can be used in physiotherapy studies. In the thesis process, a theoretical framework was built on data related to pelvic floor physiotherapy and the educational material was based on it. Feedback on the educational material was collected from physiotherapy student and teachers at the Karelia University of Applied Sciences as well as from physiotherapy practitioners. One development idea is to produce educational material on pelvic floor physiotherapy for neurological patients

Circulating metabolome landscape in Lynch syndrome

Circulating metabolites systemically reflect cellular processes and can modulate the tissue microenvironment in complex ways, potentially impacting cancer initiation processes. Genetic background increases cancer risk in individuals with Lynch syndrome; however, not all carriers develop cancer. Various lifestyle factors can influence Lynch syndrome cancer risk, and lifestyle choices actively shape systemic metabolism, with circulating metabolites potentially serving as the mechanical link between lifestyle and cancer risk. This study aims to characterize the circulating metabolome of Lynch syndrome carriers, shedding light on the energy metabolism status in this cancer predisposition syndrome.This study consists of a three-group cross-sectional analysis to compare the circulating metabolome of cancer-free Lynch syndrome carriers, sporadic colorectal cancer (CRC) patients, and healthy non-carrier controls. We detected elevated levels of circulating cholesterol, lipids, and lipoproteins in LS carriers. Furthermore, we unveiled that Lynch syndrome carriers and CRC patients displayed similar alterations compared to healthy non-carriers in circulating amino acid and ketone body profiles. Overall, cancer-free Lynch syndrome carriers showed a unique circulating metabolome landscape.This study provides valuable insights into the systemic metabolic landscape of Lynch syndrome individuals. The findings hint at shared metabolic patterns between cancer-free Lynch syndrome carriers and CRC patients.Peer reviewe