Spatial transcriptomics is revolutionizing modern biology, offering researchers an unprecedented ability to unravel intricate gene expression patterns within tissues. From pioneering techniques to newly commercialized platforms, the field of spatial transcriptomics has evolved rapidly, ushering in a new era of understanding across various disciplines, from developmental biology to disease research. This dynamic expansion is reflected in the rapidly growing number of technologies and data analysis techniques developed and introduced. However, the expanding landscape presents a considerable challenge for researchers, especially newcomers to the field, as staying informed about these advancements becomes increasingly complex. To address this challenge, we have prepared an updated review with a particular focus on technologies that have reached commercialization and are, therefore, accessible to a broad spectrum of potential new users. In this review, we present the fundamental principles of spatial transcriptomic methods, discuss the challenges in data analysis, provide insights into experimental considerations, offer information about available resources for spatial transcriptomics, and conclude with a guide for method selection and a forward-looking perspective. Our aim is to serve as a guiding resource for both experienced users and newcomers navigating the complex realm of spatial transcriptomics in this era of rapid development. We intend to equip researchers with the necessary knowledge to make informed decisions and contribute to the cutting-edge research that spatial transcriptomics offers.
- Klíčová slova
- Commercial platforms, Selection guide, Spatial transcriptomics, Technologies,
- MeSH
- lidé MeSH
- stanovení celkové genové exprese * metody MeSH
- transkriptom * MeSH
- výpočetní biologie metody MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Some medically important viruses-including retroviruses, flaviviruses, coronaviruses, and herpesviruses-code for a protease, which is indispensable for viral maturation and pathogenesis. Viral protease inhibitors have become an important class of antiviral drugs. Development of the first-in-class viral protease inhibitor saquinavir, which targets HIV protease, started a new era in the treatment of chronic viral diseases. Combining several drugs that target different steps of the viral life cycle enables use of lower doses of individual drugs (and thereby reduction of potential side effects, which frequently occur during long term therapy) and reduces drug-resistance development. Currently, several HIV and HCV protease inhibitors are routinely used in clinical practice. In addition, a drug including an inhibitor of SARS-CoV-2 main protease, nirmatrelvir (co-administered with a pharmacokinetic booster ritonavir as Paxlovid®), was recently authorized for emergency use. This review summarizes the basic features of the proteases of human immunodeficiency virus (HIV), hepatitis C virus (HCV), and SARS-CoV-2 and discusses the properties of their inhibitors in clinical use, as well as development of compounds in the pipeline.
- MeSH
- antivirové látky farmakologie terapeutické užití MeSH
- COVID-19 * MeSH
- HIV infekce * farmakoterapie MeSH
- lidé MeSH
- SARS-CoV-2 MeSH
- virové proteasy MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- antivirové látky MeSH
- nirmatrelvir and ritonavir drug combination MeSH Prohlížeč
- virové proteasy MeSH
- MeSH
- cirkulující nádorová DNA analýza MeSH
- lidé MeSH
- nádorové biomarkery analýza MeSH
- nádorové cirkulující buňky patologie MeSH
- nádory diagnóza patologie MeSH
- tekutá biopsie metody MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- úvodníky MeSH
- Názvy látek
- cirkulující nádorová DNA MeSH
- nádorové biomarkery MeSH
Successful treatment of cancer depends on early diagnosis and effective monitoring of patients' response to therapy. Traditional tools based on tumor biopsies lack the sensitivity and specificity to capture cancer development in its early phases and are not applicable for continuous monitoring. To overcome these barriers, liquid biopsies have been introduced as a minimally invasive and cost-efficient means of diagnosis with high level of specificity and sensitivity. Traditionally, liquid biopsy markers include circulating tumor cells and circulating tumor DNA. During the last decade, a new promising group of biomarkers has appeared and its utilization for cancer diagnosis and monitoring is intensively studied - the microRNAs (miRNAs). In this review, we provide a comprehensive overview of circulating miRNA analysis. We highlight the importance of sampling and quality control, discuss the technical aspects of miRNA extraction and quantification, summarize recommendations for downstream analysis and conclude with future perspectives. Taken together, we present the current state of knowledge in the field of miRNA analysis in liquid biopsies and the expected development and standardization.
- Klíčová slova
- Cancer, Circulating miRNA, Liquid biopsies, RNA-Seq, RT-qPCR,
- MeSH
- cirkulující mikroRNA analýza izolace a purifikace MeSH
- lidé MeSH
- nádorové biomarkery genetika MeSH
- nádory diagnóza genetika terapie MeSH
- odběr biologického vzorku metody MeSH
- řízení kvality MeSH
- tekutá biopsie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- cirkulující mikroRNA MeSH
- nádorové biomarkery MeSH
MicroRNA-215 (miR-215) is one of the extensively studied microRNAs (miRNAs) in human diseases, especially in different types of cancer, where it plays various roles in the initiation and progression of tumors. There is also a high conservation of miR-215 among wide range of different species indicating that this miRNA may have vital functions that are maintained during evolution. During the last ten years, significant efforts were dedicated to uncover molecular mechanisms of miR-215 regulation and cellular functioning. In addition, miR-215 was repeatedly identified to have the causal roles in pathology of various diseases, where it may serve as a promising diagnostic, prognostic or predictive biomarker and as a therapeutic target. Here, we overview more than 150 reports focused on miR-215 to allow the synthesis of knowledge on its transcriptional and post-transcriptional regulation, and functioning in essential biological processes like cell and tissue development, cell survival, cell cycle and proliferation, cell migration and invasion, cellular microenvironment communication, and metabolism. Further, we summarized the findings on miR-215 roles in pathology of nonmalignant diseases and various types of cancer with special focus on miR-215 as a promising molecule for future development of theranostic miRNA-based approaches. Although it is difficult to evaluate the full theranostic potential of miR-215, it is probable that during the following years, an increasing number of theranostic miRNA modalities that overcome the current technological obstacles will appear, and enable the translation of miR-215 knowledge into the clinic.
- Klíčová slova
- Apoptosis, Biomarker, Cell cycle, Proliferation, Therapeutic target, miR-215,
- MeSH
- cílená molekulární terapie MeSH
- lidé MeSH
- mikro RNA terapeutické užití MeSH
- nádorové mikroprostředí MeSH
- nádory genetika terapie MeSH
- regulace genové exprese u nádorů MeSH
- teranostická nanomedicína * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- mikro RNA MeSH
New non-invasive approaches that can complement and improve on current strategies for colorectal cancer (CRC) screening and management are urgently needed. A growing number of publications have documented that components of tumors, which are shed into the circulation, can be detected in the form of liquid biopsies and can be used to detect CRC at early stages, to predict response to certain therapies and to detect CRC recurrence in a minimally invasive way. The analysis of circulating tumor DNA (ctDNA), tumor-derived cells (CTC, circulating tumor cells) or circulating microRNA (miRNA) in blood and other body fluids, have a great potential to improve different aspects of CRC management. The challenge now is to find which types of components, biofluids and detection methods would be the most suitable to be applied in the different steps of CRC detection and treatment. This chapter will provide an up to date review on ctDNA, CTCs and circulating miRNAs as new biomarkers for CRC, either for clinical management or early detection, highlighting their advantages and limitations.
- Klíčová slova
- Cell-free DNA, Circulating tumor cells (CTC), Liquid biopsy, MicroRNA, Prognosis, Screening,
- MeSH
- časná detekce nádoru MeSH
- cirkulující mikroRNA MeSH
- cirkulující nádorová DNA MeSH
- kolorektální nádory krev diagnóza etiologie terapie MeSH
- lidé MeSH
- management nemoci MeSH
- nádorové biomarkery krev MeSH
- nádorové cirkulující buňky MeSH
- prognóza MeSH
- tekutá biopsie metody MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- cirkulující mikroRNA MeSH
- cirkulující nádorová DNA MeSH
- nádorové biomarkery MeSH
Colorectal cancer (CRC) incidence changes with time and by variations in diet and lifestyle, as evidenced historically by migrant studies and recently by extensive epidemiologic evidence. The worldwide heterogeneity in CRC incidence is strongly suggestive of etiological involvement of environmental exposures, particularly lifestyle and diet. It is established that physical inactivity, obesity and some dietary factors (red/processed meats, alcohol) are positively associated with CRC, while healthy lifestyle habits show inverse associations. Mechanistic evidence shows that lifestyle and dietary components that contribute to energy excess are linked with increased CRC via metabolic dysfunction, inflammation, oxidative stress, bacterial dysbiosis and breakdown of gut barrier integrity while the reverse is apparent for components associated with decreased risk. This chapter will review the available evidence on lifestyle and dietary factors in CRC etiology and their underlying mechanisms in CRC development. This short review will also touch upon available information on potential gene-environment interactions, molecular sub-types of CRC and anatomical sub-sites within the colorectum.
- Klíčová slova
- Colorectal cancer, Diet, Environment, Etiology, Genetic interactions, Lifestyle, Mechanisms, Obesity,
- MeSH
- dieta * MeSH
- genetická predispozice k nemoci MeSH
- hodnocení rizik MeSH
- interakce genů a prostředí MeSH
- interakce hostitele a patogenu MeSH
- kolorektální nádory epidemiologie etiologie MeSH
- léky na předpis škodlivé účinky MeSH
- lidé MeSH
- náchylnost k nemoci * MeSH
- obezita komplikace metabolismus MeSH
- rizikové faktory MeSH
- životní prostředí * MeSH
- životní styl * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- léky na předpis MeSH
Colorectal carcinogenesis is a multistep process involving the accumulation of genetic alterations over time that ultimately leads to disease progression and metastasis. Binding of transcription factors to gene promoter regions alone cannot explain the complex regulation pattern of gene expression during this process. It is the chromatin structure that allows for a high grade of regulatory flexibility for gene expression. Posttranslational modifications on histone proteins such as acetylation, methylation, or phosphorylation determine the accessibility of transcription factors to DNA. DNA methylation, a chemical modification of DNA that modulates chromatin structure and gene transcription acts in concert with these chromatin conformation alterations. Another epigenetic mechanism regulating gene expression is represented by small non-coding RNAs. Only very recently epigenetic alterations have been included in molecular subtype classification of colorectal cancer (CRC). In this chapter, we will provide examples of the different epigenetic players, focus on their role for epithelial-mesenchymal transition and metastatic processes and discuss their prognostic value in CRC.
- Klíčová slova
- Chromatin remodeling, Colorectal cancer, DNA methylation, Epigenetics, Epithelial-to-mesenchymal transition, Histone modifications, Prognosis, Stemness, miRNA,
- MeSH
- chromatin genetika metabolismus MeSH
- epigeneze genetická * MeSH
- epitelo-mezenchymální tranzice MeSH
- genetická epistáze MeSH
- histony metabolismus MeSH
- kolorektální nádory genetika metabolismus patologie MeSH
- lidé MeSH
- metylace DNA * MeSH
- nádorová transformace buněk genetika metabolismus MeSH
- posttranslační úpravy proteinů MeSH
- progrese nemoci MeSH
- regulace genové exprese u nádorů MeSH
- restrukturace chromatinu genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- chromatin MeSH
- histony MeSH
This review provides evidence for the importance of white and brown adipose tissue (i.e. WAT and BAT) function for the maintenance of healthy metabolic phenotype and its preservation in response to omega-3 polyunsaturated fatty acids (omega-3 PUFA), namely in the context of diseased states linked to aberrant accumulation of body fat, systemic low-grade inflammation, dyslipidemia and insulin resistance. More specifically, the review deals with (i) the concept of immunometabolism, i.e. how adipose-resident immune cells and adipocytes affect each other and define the immune-metabolic interface; and (ii) the characteristic features of "healthy adipocytes" in WAT, which are relatively small fat cells endowed with a high capacity for mitochondrial oxidative phosphorylation, triacylglycerol/fatty acid (TAG/FA) cycling and de novo lipogenesis (DNL). The intrinsic metabolic features of WAT and their flexible regulations, reflecting the presence of "healthy adipocytes", provide beneficial local and systemic effects, including (i) protection against in situ endoplasmic reticulum stress and related inflammatory response during activation of adipocyte lipolysis; (ii) prevention of ectopic fat accumulation and dyslipidemia caused by increased hepatic VLDL synthesis, as well as prevention of lipotoxic damage of insulin signaling in extra-adipose tissues; and also (iii) increased synthesis of anti-inflammatory and insulin-sensitizing lipid mediators with pro-resolving properties, including the branched fatty acid esters of hydroxy fatty acids (FAHFAs), also depending on the activity of DNL in WAT. The "healthy adipocytes" phenotype can be induced in WAT of obese mice in response to various stimuli including dietary omega-3 PUFA, especially when combined with moderate calorie restriction, and possibly also with other life style (e.g. physical activity) or pharmacological (e.g. thiazolidinediones) interventions. While omega-3 PUFA could exert beneficial systemic effects by improving immunometabolism of WAT without a concomitant induction of BAT, it is currently not clear whether the metabolic effects of the combined intervention using omega-3 PUFA and calorie restriction or thiazolidinediones depend also on the activation of BAT function and/or the induction of brite/beige adipocytes in WAT. It remains to be established why omega-3 PUFA intervention in type 2 diabetic subjects does not improve insulin sensitivity and glucose homeostasis despite inducing various anti-inflammatory mediators in WAT, including the recently discovered docosahexaenoyl esters of hydroxy linoleic acid, the lipokines from the FAHFA family, as well as several endocannabinoid-related anti-inflammatory lipids. To answer the question whether and to which extent omega-3 PUFA supplementation could promote the formation of "healthy adipocytes" in WAT of human subjects, namely in the obese insulin-resistant patients, represents a challenging task that is of great importance for the treatment of some serious non-communicable diseases.
- Klíčová slova
- Adipocytes, Bioavailability, Fish oil, Immunometabolism, Lipid mediators, de novo lipogenesis,
- MeSH
- bílá tuková tkáň účinky léků metabolismus MeSH
- inzulinová rezistence genetika MeSH
- kyseliny mastné omega-3 metabolismus terapeutické užití MeSH
- lidé MeSH
- lipolýza účinky léků MeSH
- metabolismus lipidů účinky léků genetika MeSH
- obezita dietoterapie genetika metabolismus MeSH
- tukové buňky účinky léků metabolismus MeSH
- zánět dietoterapie genetika metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- kyseliny mastné omega-3 MeSH
