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Epigenetics of oogenesis
No full textEpigenetic changes include all modifications affecting the expression of genes without changing the nucleotide sequence of the genome. Most studied epigenetic changes include DNA methylation, histone alterations and non-coding RNAs. DNA methylation is an important epigenetic mark, protecting the genome during gametogenesis and early embryo development. Demethylation process is a genome-wide event, taking place in two distinct waves during gametogenesis. The first event helps restore naïve pluripotency of the zygote, while the second event aids in the loss of parental epigenetic memory and facilitates specification of gametes. Histone modifications were recognized in murine and human primordial germ cells where their subsets condense chromatin, protecting it from dynamic changes taking place during gamete maturation. Deacetylation of histones was recognized as an important prerequisite of chromosomal segregation during metaphase II. Germline-specific ncRNAs and piRNAs are important in inhibiting transposon activity during gametogenesis, protecting overall genome stability. All epigenetic changes are prone to disruption, especially by exogenous factors. In recent years, with the increase in infertility, the association between assisted reproductive technology (ART) and its effects on epigenome remodeling of gametes have gained importance. The aim of this review is to summarize the epigenetic modifications crucial for oocyte development, while highlighting their role in reproductive disorders and ART
ON KANT’S CONTRIBUTION TO THE COOPERATION OF PHILOSOPHY AND MEDICINE THROUGH EXAMPLES OF REASON AND BODY
No full textCausal factors of the pertussis epidemic
No full textHripavac je akutna zarazna bolest uzrokovana bakterijom Bordetella pertussis čija su glavna karakteristika napadaji spazmatičnog kašlja koji završavaju forsiranim inspirijem, a ponekad i povraćanjem. Od hripavca najčešće obolijevaju mala djeca. U doba prije uvođenja antibiotske terapije i cjepiva, hripavac je uzrokovao veću smrtnost male djece nego bilo koja druga akutna zarazna bolest. Postoje cjelostanična i acelularna cjepiva protiv hripavca koja se razlikuju po reaktogenosti i imunogenosti, no oba cjepiva su se pokazala učinkovitim u suzbijanju broja oboljelih od hripavca. Nedavni porasti broja slučajeva postavljaju pitanje o sposobnosti acelularnog cjepiva da optimalno podrži dugoročnu zaštitu. Oba su cjepiva sigurna i štite populaciju od hripavca. Slabija učinkovitost cjepiva tijekom vremena, niska procijepljenost ili nepravovremeno cijepljenje uvelike pridonose pojavama epidemija. Za kontrolu hripavca i zaštitu osjetljivih skupina ključna je visoka procijepljenost protiv uzročnika koja značajno smanjuje broj slučajeva i izbijanje epidemija.Whooping cough is an acute infectious disease caused by the bacterium Bordetella pertussis, characterized by episodes of spasmodic coughing that end with forced inhalation, and sometimes vomiting. It most commonly affects young children. Before the introduction of antibiotic therapy and vaccines, pertussis caused higher mortality in young children than any other acute infectious disease. There are whole-cell and acellular vaccines against pertussis, which differ in reactogenicity and immunogenicity, but both have proven effective in reducing the number of cases. Recent increases in cases raise questions about the ability of the acellular vaccine to optimally support long-term protection. Both vaccines are safe and protect the population against pertussis. Lower vaccine effectiveness over time, low vaccination coverage, or untimely vaccination greatly contribute to outbreaks. High vaccination coverage is key to controlling pertussis and protecting vulnerable groups, significantly reducing the number of cases and outbreaks
GENETIC ANALYSIS IN PEDIATRIC INTESIVE CARE AT KBC RIJEKA - RETROSPECTIVE ANALYSIS
No full textRazvojem medicinske genetike i sve većom implementacijom genetskog testiranja došlo je do njezine integracije u gotovo sve dijelove medicine. Cilj ovog retrospektivnog istraživanja bio je prikaz otkrivenih genetskih poremećaja, te koje su se metode koristile za otkrivanje istih. Ovim istraživanjem obuhvaćena su sva djeca koja su liječena u JILu Klinike za pedijatriju, KBC-a Rijeka u je vremenskom razdoblju od 01. siječnja 2018. godine do 31. prosinca 2023. godine. Analizirani su slijedeći podatci: dob, spol, razlog upućivanja na genetsku analizu, rezultate genetske analize te korištene metode. Od 2018. do 2023. godine u istraživanju je sudjelovalo ukupno 28 ispitanika. Od ukupnog broja ispitanika 13 je muškog (46%), a 15 ženskog spola (54%). Najzastupljeniju dobnu skupinu čine djeca mlađa od godine dana života (68%). Najčešća indikacija za testiranje je kardiološka bolesti (29%). Kod najvećeg broja ispitanika (68%) korištena je NGS metoda. Pozitivni rezultati testiranja dobiveni su u 46% slučajeva. Dobiveni rezultati ukazuju na porast broja provedenih genetskih testiranja u razdoblju od 2018. do 2023. za 100% što ukazuje na povećanje dostupnosti genetičkog testiranja kao i povećanje njegove primjene u kliničkoj praksi.The development od medical genetics and its increasing implementation of genetic testing led to its integration into almost all areas of medicine. The aim of this retrospective study was to present the detected genetic disorders and which method were used to detect them. This research covers the period from January 1, 2018 to December 31, 2023 and includes the following data: age, gender, primary group of diseases, results and methods used for genetic analysis. From 2018. to 2023. a total of 28 patients participated in the study, 13 were male (46 %) and 15 were female (54%). The most common age group was patients under the age of one (68%). The most common indications for genetic testing were cardiac diseases (29%) . The most commonly used genetic method was NGS (68%). Positive results were obtained in 46% of cases.Given results indicate a 100% increase in the number of genetics test performed in the period from 2018 to 2023, which shows an increase in the availability of genetic testing as well as an increase in its application in clinical practice
Possible applications of additive technologies in head and neck surgery with an emphasis on the fabrication of epitheses
No full textAditivne tehnologije mogu se definirati kao proizvodni procesi koji se temelje na dodavanju materijala po principu sloj-na-sloj kako bi se postupno formirao proizvod. Počinju se razvijati 1980-ih godina i predstavljaju jedan od najvažniji napredaka u proizvodnji, a medicina je jedna od grana u kojoj se najčešće koriste, uvelike zbog toga jer omogućuju primjenu personalizirane medicine u liječenju svakog pacijenta, i to u fazi rehabilitacije, rekonstrukcije i regeneracije tkiva. Prije proizvodnje aditivnim tehnologijama potrebno je kreirati digitalni model proizvoda uz pomoć CAD tehnologije. Za samu proizvodnju koriste se 3D pisači ili printeri. Aditivne tehnologije dijele se u sedam glavnih kategorija: fuzija praškastog sloja, ekstruzija materijala, foto-polimerizacija u komori, raspršivanje veziva, raspršivanje materijala, laminiranje listova i taloženje usmjerenim izvorom energije. Materijali koji se koriste mogu se podijeliti u plastike, metale i keramike. U medicini se za proizvodnju plastičnih predmeta najčešće koriste materijali poput ABS, PLA, PEEK, PA, te razne vrste smola, a najčešće korištene tehnologije su FDM, SLS i SLA. Za proizvodnju metalnih predmeta koriste se DMLS i SLM tehnologije, a najčešći materijal je titanij. Primjena aditivnih tehnologija u medicini može se kategorizirati u pet skupina. To su bioproizvodnja, implantati, medicinski modeli, potom alati, instrumenti i dijelovi medicinskih uređaja, te na kraju skupina medicinskih pomagala, vodilica, udlaga i proteza, uključujući epiteza koje pomažu u obnovi estetike glave i vrata. Prednosti proizvodnje uz pomoć aditivnih tehnologija uključuju raznolikost materijala sa specijaliziranim svojstvima, mogućnost proizvodnje kompleksnih geometrijskih oblika, brz i jeftin razvoj prototipova, te mogućnost proizvodnje unikatnih proizvoda ili malih serija proizvoda.Additive technologies can be defined as manufacturing processes based on adding material layer by layer to gradually form a product. They began to develop in the 1980s and represent one of the most significant advances in manufacturing. Medicine is one of the fields where they are most frequently used because they enable a personalized medicine approach in the treatment of each patient in rehabilitation, reconstruction, and tissue regeneration phases. Before production with additive technologies, it is necessary to create a digital model of the product with the help of CAD technology. For production itself, 3D printers are used. Additive technologies are divided into seven main categories: powder bed fusion, material extrusion, vat photopolymerization, binder jetting, material jetting, sheet lamination, and directed energy deposition. The materials used can be categorized into plastics, metals, and ceramics. In medicine, materials such as ABS, PLA, PEEK, PA, and various types of resins are often used for producing plastic items, with FDM, SLS, and SLA being the most commonly used technologies. For producing metal items, DMLS and SLM technologies are used, with titanium being the most common material. The application of additive technologies in medicine can be categorized into five groups: biomanufacturing, implants, medical models, tools, instruments and parts of medical devices, and finally, a group containing medical aids, guides, splints, and prostheses, including epitheses that help restore the aesthetics of the head and neck. The advantages of production using additive technologies include a variety of materials with specialized properties, the ability to produce complex geometric shapes, rapid and cost-effective prototype development, and the ability to produce unique products or small series of products
Immunometabolic cell profile in intermittent hypoxia
No full textHipoksija je stanje koje je obilježeno nedostatkom kisika u stanicama i tkivima koje ima bitnu ulogu u brojnim patološkim stanjima. Ključni mehanizam koji regulira stanične procese u uvjetima hipoksije jest aktivacija hipoksijom potaknutih čimbenika (HIF). HIF aktiviraju osjetljivi stanični senzori kisika, a sam HIF regulira kompleksnu mrežu staničnih signalnih puteva koji kontroliraju adaptivne odgovore na hipoksiju. Kategorizirane su tri vrste hipoksije i karakterizirani parametri akutne, kronične te intermitentne hipoksije. Intermitentna hipoksija (IH) označava cikličko izmjenjivanje perioda hipoksije s periodima reoksigenacije. IH se pojavljuje u nekim patološkim stanjima poput opstruktivne apneje u spavanju, dok se u drugim stanjima pokazala kao vrlo protektivan čimbenik koji značajno poboljšava klinički ishod. Intermitentna hipoksija posreduje neuroprotektivne i kardioprotektivne učinke kroz modulaciju upalnog odgovora djelujući na nuklearni faktor κB (NF-κB) signalni put, povećanjem aktivnosti antioksidativnog sustava, prilagodbom energijskog metabolizma stanice prema anaerobnoj glikolizi, sprječavanjem apoptoze te aktivacijom drugih adaptivnih signalnih puteva i gena. Za pojavu zaštitnih mehanizama intermitentne hipoksije zaslužni su brojni signalni putevi, no glavni medijatori su HIF-1α, nuklearni faktor 2 povezan s eritroidnim faktorom 2, NF-κB, eritropoetin, vaskularni endotelni čimbenik rasta i drugih čija je uloga objašnjena u ovom radu.Hypoxia is a condition characterized by a lack of oxygen in cells and tissues that plays a crucial role in numerous pathological conditions. The key mechanism that regulates cellular processes in hypoxic conditions is the activation of hypoxia-inducible factors (HIFs). HIF is activated by sensitive cellular oxygen sensors, while activated HIF regulates a complex network of cellular signaling pathways that control adaptive responses to hypoxia. There are categorised three types of hypoxia and it’s parameters for acute, chronic, and intermittent hypoxia. Intermittent hypoxia (IH) involves cyclic shifts between hypoxic periods and reoxygenation periods. IH is present in specific pathological conditions like obstructive sleep apnea, while in other cases, it is a significant protective factor that notably enhances clinical outcomes. Intermittent hypoxia mediates neuroprotective and cardioprotective effects through modulating the inflammatory response by acting on the nuclear factor κB (NF-κB) signaling pathway, increasing the activity of the antioxidant system, adjusting cellular energy metabolism towards anaerobic glycolysis, preventing apoptosis, and activating other adaptive signaling pathways and genes. Various signaling pathways contribute to the development of protective mechanisms of intermittent hypoxia, with the primary mediators being HIF-1α, nuclear factor erythroid 2-related factor 2, NF-κB, erythropoietin, vascular endothelial growth factor, and others whose roles are elucidated in this thesis
Antitumor activity of stearyl glycyrrhetinate in colon cancer cells
No full textRak debelog crijeva jedan je od vodećih uzroka pobola i pomora u svijetu sa gotovo 2 milijuna novooboljelih godišnje te treći najčešće dijagnosticirani oblik karcinoma. Cilj ovog istraživanja bio je pokazati učinak 18β-gliciretinske kiseline (18β-GK) i stearil gliciretinata (SG) na stanice raka debelog crijeva HCT116. Bioaktivni pentaciklički triterpenoid, 18β-GK i njezin stearil ester SG, analizom vitalnosti stanica (XTT test) pokazali su smanjenje stanične vitalnosti HCT116 stanica (rak debelog crijeva) ovisno o primjenjivanoj dozi. 18β-GK postigla je IC50 vrijednost od 245,08 µM dok je SG postigao pet puta nižu IC50 vrijednost od 35,28 µM. Obzirom na bolji učinak u smanjenju vitalnosti tumorskih stanica SG u odnosu na 18β-GK, u manjoj dozi, pokazani su mehanizmi kojima SG postiže svoje protutumorsko djelovanje. Western blot analizom pokazan je učinak SG na promjenu izražaja proteina od interesa. SG, ovisno o dozi (10, 15, 20 i 25 µM) povećao je izražaj inhibitora staničnog ciklusa, p21. Izražaj p-AMPKα Thr172 (aktivacija AMPKα), ovisno o dozi SG, se povisio ukazujući na sniženje količine ATP-a u stanicama, odnosno povećanje omjera AMP/ATP. Spektrofotometrijska analiza potrošnje glukoze mjerenjem u staničnom mediju pokazala je kako tretman SG-om umanjuje potrošnju glukoze ovisno o dozi. SG je sukladno tome povećao izražaj proteina autofagije, LC3B II. Analizom izražaja PARP-a, markera apoptoze u slučaju njegovog cijepanja, pokazano je kako stanice nisu aktivirale apoptozu, već autofagiju. Kotretman s 3-metiladeninom (3-MA), inhibitorom autofagije, pokazao je zaštitni učinak, sugerirajući aktivaciju citotoksične autofagije u tretmanu sa SG. Rezultati trenutnog istraživanja daju uvid u mehanizam djelovanja i antitumorski potencijal SG u liječenju tumora debelog crijeva kroz aktivaciju citotoksične autofagije.Colon cancer is one of the leading causes of illness and death in the world, with almost 2 million new cases per year, and the third most frequently diagnosed form of cancer. The aim of this study was to demonstrate the effect of 18β-glycyrrhetinic acid (18β-GA) and stearyl glycyrrhetinate (SG) on HCT116 colon cancer cells. The bioactive pentacyclic triterpenoid, 18β-glycyrrhetinic acid and its stearyl ester SG, showed a decrease in the cell viability of HCT116 cells (colon cancer) depending on the applied dose, using the cell viability analysis (XTT test). 18β-GA achieved an IC50 value of 245,08 µM while SG achieved a fivefold lower IC50 value of 35,28 µM. Considering the better effect in reducing the viability of SG tumor cells compared to 18β-GA, in a lower dose, the mechanisms by which SG achieves its antitumor effect have been demonstrated. Western blot analysis showed the effect of SG on the change in the expression of the protein of interest. SG, dose-dependently (10, 15, 20 and 25 µM) increased the expression of the cell cycle inhibitor, p21. The expression of p-AMPKα Thr172 (AMPKα activation), depending on the dose of SG, increased, indicating a decrease in the amount of ATP in the cells, i.e. an increase in the AMP/ATP ratio. Spectrophotometric analysis of glucose consumption by measurement in the cell medium showed that treatment with SG reduces glucose consumption in a dose-dependent manner. Accordingly, SG increased the expression of the autophagy protein, LC3B II. Analysis of the expression of PARP, a marker of apoptosis in case of its cleavage, showed that the cells did not activate apoptosis, but autophagy. Co-treatment with 3-methyladenine (3-MA), an autophagy inhibitor, showed a protective effect, suggesting activation of cytotoxic autophagy in SG treatment. The results of the current research provide insight into the mechanism of action and the antitumor potential of SG in the treatment of colon tumors through the activation of cytotoxic autophagy
Microinvasive cervical cancer
No full textMikroinvazivni rak vrata maternice klasificira se kao mikroskopska lezija čija dubina u stromu od baze epitela ne prelazi 5 mm. Stadij IA dijeli se još na stadij IA1 i na stadij IA2. Žene s mikroinvazivnim rakom vrata maternice obično su asimptomatske, bez subjektivnih tegoba. Simptomi, kada su prisutni, obično su ograničeni na međumenstrualno ili postkoitalno krvarenje. Dijagnoza mikroinvazivnog raka vrta maternice postavlja se isključivo patohistološkom analizom suspektne lezije. Uzorak tkiva potreban za patohistološku analizu dobiva se ekscizijskom biopsiom. Ekscizijske biopsije jesu postupci kod kojih dobiveni uzorci tkiva predstavljaju dijelove tkiva cerviksa konusnog oblika, a uključuju donji dio endocervikalnog kanala te dio egzocerviksa. Nakon određivanja kliničkog stadija mikroinvazivnog raka vrata maternice odlučuje se i izabire što je moguće poštedniji oblik liječenja. Zbog niskog rizika širenja bolesti u parametrijalne i uterosakralne limfne čvorove, lezije stadija IA1 liječe se konizacijom. Konizacija je ujedno i tretman izbora za mlade pacijentice koje žele očuvati svoju reproduktivnu sposobnost. Međutim, ukoliko je žena završila s reprodukcijom tada prednost ima histerektomija tipa A. Ako u stadiju IA1 mikroinvazivnog raka vrata maternice postoji invazija limfovaskularnog prostora, time se značajno povećava i rizik od metastaza u limfnim čvorovima te se iz tog razloga uz konizaciju učini i zdjelična limfadenektomija. U liječenju stadija IA2 najprihvatljivije je učiniti histerektomiju sa zdjeličnom limfadenektomijom. U bolesnica mlađih od 35 godina, da bi sačuvale plodnost, izvodi se trahelektomija sa zdjeličnom limfadenektomijom. Općenito, kada se radi o mikroinvazivnom raku vrata maternice, riječ je o malim lezijama koje u pravilu imaju dobru prognozu s visokom stopom petogodišnjeg preživljenja i malim rizikom od pojave recidiva.Microinvasive cervical cancer is classified as a microscopic lesion in which the depth of invasion should not be greater than 5 mm from the base of the epithelium. Stage IA is further subdivided into two stages, stage IA1 and stage IA2. Women with microinvasive cervical cancer are usually asymptomatic, without subjective complaints. Symptoms, when they are present, are usually limited to intermenstrual or postcoital bleeding. The diagnosis of microinvasion can only be made by pathohistological analysis of the suspected lesion. The specimen required for pathohistological analysis is obtained by excisional biopsy. Excisional biopsies are procedures in which the obtained tissue samples represent parts of the cervical tissue in a conical shape, and include the lower part of the endocervical canal and part of the exocervix. Once the clinical stage of microinvasive cervical cancer is confirmed, the method of treatment may be decided, which should always be done as sparingly as possible. Since there is a small risk of lymph node metastases to the parametrial and uterosacral lymph nodes, stage IA1 lesions are treated with conization. Conization is the treatment of choice for young patients wishing to preserve their fertility. However, in women who have completed childbearing or in elderly women a hysterectomy type A is preferred. If there is invasion of the lymphovascular space in stage IA1 microinvasive cervical cancer, there is a significant risk of metastases in the lymph nodes and for this reason hysterectomy and pelvic lymphadenectomy are used as the first choice of treatment. In the treatment of stage IA2, it is most acceptable to perform a radical hysterectomy with pelvic lymphadenectomy. The most acceptable treatment of stage IA2 is to perform a radical hysterectomy with pelvic lymphadenectomy In patients under the 35 years old, in order to preserve fertility, trachelectomy with pelvic lymphadenectomy is performed. In general, microinvasive cervical cancer represents small lesions that usually have a good prognosis with a high five-year survival rate and a low risk of recurrence
Reply to Saleh, C. Comment on “Bažadona et al. The Interconnection between Carotid Intima–Media Thickness and Obesity: Anthropometric, Clinical and Biochemical Correlations. Medicina 2023, 59, 1512”
No full textWe would like to begin by expressing our gratitude for the interest shown in our research [1,2].
We agree that a composite carotid intima–media thickness (CIMT) measurement that includes the common carotid artery (CCA), the carotid bifurcation and internal carotid artery (ICA) could provide more accurate measurement, but this type of measurement was not conducted for several reasons. First, as already mentioned, there is no universally accepted standardized measurement protocol and most studies were performed using only CCA IMT [3]. CCA IMT is a well-known marker of atherosclerosis and its association with cardiovascular and cerebrovascular events has been proven repeatedly [4,5,6]. The measurement of CCA IMT is easier to obtain and is highly reliable with less variability in measurements [6,7].
To conclude, although we agree our study protocol has its limitations, we believe that it provided more feasible patient examination and more comparable results
The Next Chapter in Cancer Diagnostics: Advances in HPV-Positive Head and Neck Cancer
No full textHuman papillomavirus (HPV)-associated head and neck squamous cell carcinoma (HNSCC), particularly oropharyngeal squamous cell carcinoma (OPSCC), is an increasingly prevalent pathology worldwide, especially in developed countries. For diagnosing HPV in HNSCC, the combination of p16 immunohistochemistry (IHC) and polymerase chain reaction (PCR) offers high sensitivity and specificity, with p16 IHC being a reliable initial screen and PCR confirming HPV presence. Advanced techniques like next-generation sequencing (NGS) and RNA-based assays provide detailed insights but are primarily used in research settings. Regardless of HPV status, standard oncological treatments currently include surgery, radiation, and/or chemotherapy. This conventional approach does not account for the typically better prognosis of HPV-positive HNSCC patients, leading to increased chemo/radiation-induced secondary morbidities and reduced quality of life. Therefore, it is crucial to identify and detect HPV positivity and other molecular characteristics of HNSCC to personalize treatment strategies. This comprehensive review aims to summarize current knowledge on various HPV detection techniques and evaluate their advantages and disadvantages, with a focus on developing methodologies to identify new biomarkers in HPV-positive HNSCC. The review discusses direct and indirect HPV examination in tumor tissue, DNA- and RNA-based detection techniques, protein-based markers, liquid biopsy potentials, immune-related markers, epigenetic markers, novel biomarkers, and emerging technologies, providing an overall insight into the current state of knowledge