Ectodermal dysplasias are a wide group of genetic disorders characterised by clinical symptoms in ectodermal derivatives (most frequently teeth, hair, nails and sweat glands). There is a number of genes, which, if mutate...Ectodermal dysplasias are a wide group of genetic disorders characterised by clinical symptoms in ectodermal derivatives (most frequently teeth, hair, nails and sweat glands). There is a number of genes, which, if mutated, can cause the specified phenotype. The molecular basis of many ectodermal dysplasias have been investigated. The phenotype often results from the imparied communication in molecular pathways important in embryonic morphogenesis or disturbed function of protein complexes involved in homeostasis, adhesion and stability of the cells in the tissue. Different classification systems have been proposed to group ectodermal dysplasias according to clinical symptoms or molecular basis. Molecular technologies have let recently to expand diagnostic abilities for ectodermal dysplasias patients. Certainly in the nearest years new genes and mutations will be discovered as a cause of ectodermal dysplasias.
The year 2021 marks not only 60 years since the discovery of messenger RNA and the genetic code. Already 100 yaers passed since RNA was discovered. On the occasion of this special anniversary, we would like to recall the...The year 2021 marks not only 60 years since the discovery of messenger RNA and the genetic code. Already 100 yaers passed since RNA was discovered. On the occasion of this special anniversary, we would like to recall the most important events in the history of nucleic acids that led to the above discoveries. We remind the beginning of a new era in science caused by the isolation of nuclein and then nucleic acid, whose components and properties were gradually learned, often by little-known researchers. The distinction of RNA and DNA and the analysis of their occurrence in cells made it possible to formulate the first conclusions about the functions of these compounds. Conclusions on the ratio of nitrogenous bases in DNA led to the knowledge of the structure of the double helix, triggering an avalanche of questions about the essence of transmission of genetic information. Answers began to emerge with the discovery of mRNA, and knowledge of the first three nucleotides encoding an amino acid caused a race to decipher the genetic code. The above discoveries are the foundation of molecular biology. The diamond jubilee coincided with the development of an mRNA-based vaccine against the SARS-CoV-2.
Photodynamic therapy (PDT) is one of the least toxic methods causing the death of cancer cells. Photosensitizer (PS) applied to a patient accumulates in the tumor, where under the appropriate wavelength and insensitivity...Photodynamic therapy (PDT) is one of the least toxic methods causing the death of cancer cells. Photosensitizer (PS) applied to a patient accumulates in the tumor, where under the appropriate wavelength and insensitivity of light is activated. Activated PS in the presence of oxygen produces reactive oxygen species (ROS), which make significant damage leading to the destruction of cancer cells by apoptosis, necrosis or autophagic process. Moreover, PDT causes an acute local inflammatory response that is involved in removing dead cells, restoring normal tissue homeostasis, and sometimes leads to the development of systemic immunity. However, some cells may survive treatment and develop resistance. Mechanisms, which lead to decrease of the level of PS in cells may be involved in the cytoprotection of cancer cells from PDT. Furthermore, increased activity of antioxidant mechanisms, overexpression of molecular chaperones and activation of survival pathways can protect cells from PDT.
Midbrain dopamine neurons along with the major target of their projections, dopaminoceptive neurons in striatum, regulate reinforcement learning and motivation. The activity and plasticity in the dopamine system are larg...Midbrain dopamine neurons along with the major target of their projections, dopaminoceptive neurons in striatum, regulate reinforcement learning and motivation. The activity and plasticity in the dopamine system are largely dependent on excitatory glutamatergic transmission. The article describes the functional role of N-methyl-D-aspartate (NMDA) receptors in driving the phasic activity in dopamine neurons, and a role of NMDA and metabotropic glutamate 5 (mGluR5) receptors in induction of plasticity in dopaminoceptive striatal medium spiny neurons. Based on published studies on genetically modified mice, the article further discusses how targeted loss of glutamate receptor-dependent signalling in dopamine system affects reinforcement learning and motivational processes. The conclusion of the article is the view that aberrant glutamate signalling in dopamine system may contribute to maladaptive behaviours, which are particularly often observed in mental disorders.
Short-chain fatty acids (SCFAs) produced in the human colon are the major products of bacterial fermentation and are believed that they have a protective effect in case of gastrointestinal diseases. SCFAs, such as acetat...Short-chain fatty acids (SCFAs) produced in the human colon are the major products of bacterial fermentation and are believed that they have a protective effect in case of gastrointestinal diseases. SCFAs, such as acetate, propionate, and butyrate are significant metabolites in intestinal homeostasis, and have been shown to be beneficial in inflammatory bowel diseases and colorectal cancer. SCFA are responsible for maintaining proper intestinal barrier and they take part in relevant immune functions. Action of SCFAs is dependent on the activation of protein receptors for receptor activation (GPCR) such as GPR41, GPR43 and GPR109A. In this review, we discuss the effects of SCFA on the intestinal mucosa in terms of inflammatory diseases and colorectal cancer.
Inflammatory bowel diseases (IBD) are a group of chronic and globally appearing conditions that significantly decrease patientsâ quality of life. The main representatives of IBD are Crohnâs disease and ulcerative colitis...Inflammatory bowel diseases (IBD) are a group of chronic and globally appearing conditions that significantly decrease patientsâ quality of life. The main representatives of IBD are Crohnâs disease and ulcerative colitis. Although the etiology of IBD is still not fully understood, the NLRP3 inflammasome is one of the most promising targets of research in this field. The NLRP3 inflammasome is a functional complex, which is activated in damage- and pathogen-associated molecular patterns-dependent manner and is responsible for production of proinflammatory interleukin(IL)-1β and IL-18, because of which it participates in the inflammatory process underlying IBD. However, in recent years the NLRP3 inflammasome has gained attention as a potential protective factor against IBD being involved in maintaining homeostasis of intestinal mucosa and controlling intestinal microbiome. In our review we discuss the role of NLRP3 inflammasome in IBD pathogenesis as both causative and protecting factor.
Constipation occurs more often in old patients, because the intestinal peristalsis decreases with aging. Constipation is caused due to impaired motility of the intestines, intestinal barrier damage and the imbalance betw...Constipation occurs more often in old patients, because the intestinal peristalsis decreases with aging. Constipation is caused due to impaired motility of the intestines, intestinal barrier damage and the imbalance between the absorption and secretion of water and electrolytes, as well as disturbed production and release of intestinal hormones, infiltration of the gastrointestinal tract with immune cells, excessive production of pro-inflammatory cytokines and the alterations in the functions of enteric nervous system. In this review we will discuss the most important issues associated with the process of aging of the digestive tract, focusing on the enteric nervous system.
Rab proteins are necessary for membrane fusion and fission and as such are key regulators of intracellular transport in eukaryotic cells. They also control other aspects of cell functioning, including the cytoskeleton re...Rab proteins are necessary for membrane fusion and fission and as such are key regulators of intracellular transport in eukaryotic cells. They also control other aspects of cell functioning, including the cytoskeleton rearrangements, determination of cell polarity or signal transduction. Rab proteins exert their control both indirectly, because they decide whether all necessary proteins and other cargo reach their correct destinations in the cell, and directly, through interactions of their active forms with effector proteins. Therefore, the results of Rab dysfunctions manifest themselves on all levels of biological organization â from cells, through tissues and organs, to whole organisms. In plants, Rab-dependent processes are important for cell architecture, differentiation, reactions to biotic and abiotic stress, as well as for the efficiency of agricultural production.
Glucose is not only the primary source of energy, but also a compound which plays an important role in the metabolism and maintenance of the proper physiological state of the cell. This is particularly pronounced in the...Glucose is not only the primary source of energy, but also a compound which plays an important role in the metabolism and maintenance of the proper physiological state of the cell. This is particularly pronounced in the case of yeasts, in which the influence of glucose on the physiological state of the cell is directly manifested. Among other by obtaining energy through fermentation or aerobic respiration depending on the availability of glucose. Glucose-dependent modulation of intracellular metabolic pathways influence on the reproductive potential and lifespan of the cells, what links glucose with calorie restriction studies. At the same time, there is a noticeable lack of data concerning the calorie excess and its consequences at the cellular level. Using the yeast Saccharomyces cerevisiae cells as a research model, a significant relationship between glucose concentration, biosynthetic efficiency, reproductive potential and total lifespan of yeast cells was found. High glucose concentrations, corresponding to the calorie excess conditions, lead to an increase in the level of reactive oxygen species, an increase in cell size and cell biomass, but at the same time, it reduces the reproductive potential and shortens the total lifespan of the yeast cell. The negative impact of glucose excess on the physiological state of the cell as well as the complexity and interrelationships of intracellular metabolic pathways suggest that the issue of glucose metabolism need further investigations.
Proteins which regulate morphogenesis of the epidermis ensure its proper construction and function and mutations or abnormal expression of those proteins impact epidermal function. One recently described protein is Recep...Proteins which regulate morphogenesis of the epidermis ensure its proper construction and function and mutations or abnormal expression of those proteins impact epidermal function. One recently described protein is Receptor Interacting Serine/Threonine Kinase 4 (RIPK4). Mutations in RIPK4 cause the autosomal-recessive form of Bartsocas-Papas syndrome and Popliteal Pterygium Syndrome the Aslan type. In mice, deletion of Ripk4 (Ripk4-/-) leads to premature death of neonates caused by numerous skin adhesions. RIPK4 regulates development and maintenance of differentiation and proliferation homeostasis of keratinocytes, as well as inflammation. RIPK4 also appears to act as a tumor suppressor in skin, since expression is decreased in squamous skin carcinoma and inducible deletion in mice facilitates induction and growth of papillomas and squamous skin carcinomas in chemical carcinogenesis. The review describes the RIP family, the engagement of RIPK4 in differentiation of the epidermis and consequences resulting from its improper expression.
DNA denaturation with High Resolution Melting PCR-HRM is a method based on the identification of differences in the denaturation of PCR reaction products in the presence of fluorescent dyes. It is used to detect genetic...DNA denaturation with High Resolution Melting PCR-HRM is a method based on the identification of differences in the denaturation of PCR reaction products in the presence of fluorescent dyes. It is used to detect genetic variation in nucleic acid sequences in many branches of science, medicine and industry. This article is a review of the current literature of the methodology, applications and development of HRM analysis, which, thanks to its advantages such as speed, low cost, flexibility and simplicity, has found many applications, and its spectrum is still expanding.
High resolution melting (HRM) is a method based on the identification of differences in the denaturation of PCR reaction products in the presence of fluorescent dyes. It allows for a detailed analysis of the genetic prof...High resolution melting (HRM) is a method based on the identification of differences in the denaturation of PCR reaction products in the presence of fluorescent dyes. It allows for a detailed analysis of the genetic profiles. In addition this analysis is low-cost, single-step, closed-tube and has high sensitivity. HRM found applications in diagnostics, laboratory and clinical researches. This article is a literature review of the applications of HRM analysis in medicine.
The microbiome of the ruminant digestive system is one of the most complex examples of the interaction between microorganisms and the host. The microbiome of the digestive system of ruminants is necessary to obtain energ...The microbiome of the ruminant digestive system is one of the most complex examples of the interaction between microorganisms and the host. The microbiome of the digestive system of ruminants is necessary to obtain energy from plant food, which would not be possible without its participation. The microbiome of the digestive system consists of bacteria, archaea, protozoa and fungi. Bacteria are the most numerous group, with Firmicutes and Bacteroidetes being the main clusters. The composition of the microbiome, both quantitatively and qualitatively, depends on factors such as diet, age, health, and the environment. Additionally, it may be influenced by genetic or biological factors (e.g. gender). Microorganisms living in the digestive system of ruminants significantly affect their health or production indicators, which in turn is associated not only with the proper absorption of nutrients from food, but also with the function of the microbiome as a specific immune system.
Autism spectrum disorder (ASD) is common early neurodevelopmental disorder characterized by a varied trajectory and symptoms which affects diagnosis and therapy. For this reason, great diagnostic and therapeutic possibil...Autism spectrum disorder (ASD) is common early neurodevelopmental disorder characterized by a varied trajectory and symptoms which affects diagnosis and therapy. For this reason, great diagnostic and therapeutic possibilities are seen in genetic studies. The aim of this review is to discuss the genetic architecture of ASD and possible therapeutic strategies.The patterns of ASD inheritance are discussed, genetic variations (including CNV polymorphisms) and the percentage of the ASD patients divided into specific classes of genetic mutations are indicated. The paper shows the most important three basic models of inheritance: polygenic, oligogenic and main gene. Molecular and cellular mechanisms linked to neurobiological models of ASD are also presented. Genetic research confirms the diversity of genetic factors involved in the ASD formation. Model systems based on the genes of the neurodevelopmental syndrome show the ability to reverse some deficits in adult patients.
Aging is a multifunctional process which is characterized by many changes on molecular, cellular and tissue levels. The chronic, sterile and low-grade inflammation process, that occurs during aging is referred to as 'inf...Aging is a multifunctional process which is characterized by many changes on molecular, cellular and tissue levels. The chronic, sterile and low-grade inflammation process, that occurs during aging is referred to as 'inflammaging'. Inflammaging is mentioned as a risk factor for the onset and progression of chronic diseases, not only age-related. Inflammaging contributes to increased morbidity and mortality in elderly individuals, and also affects the lifespan and quality of life. Cell senescence and disturbances in the regulation of inflammasome activation, mitochondrial function, autophagy and mitophagy, ubiquitin-proteasome system and the response to DNA damage contribute to the development of inflammaging. The above processes interact with each other and are modulated by signaling pathways involved in the regulation of the inflammatory response, i.e. NF-kB, mTOR, RIG-I, Notch, TGF-b, Ras pathways, and regulation of sirtuin activity. The aim of the study is to present the processes and signaling pathways underlying inflammaging, including clinical and experimental studies.
The article describes different groups of psychoactive substances, which are chemical compounds that alter perception. Based on their main effect on the psyche they were classified into four subclasses: stimulants, empat...The article describes different groups of psychoactive substances, which are chemical compounds that alter perception. Based on their main effect on the psyche they were classified into four subclasses: stimulants, empathogens, hallucinogens and depressants., Molecular mechanisms of action of different drugs of abuse were described, together with their social and economic issues in Poland and Europe.
Metastasis is of great clinical importance as it is responsible for more than 90% of cancer-related mortality. Therefore, there is a strong need to prevent metastasis formation or to target existing metastases. It is cur...Metastasis is of great clinical importance as it is responsible for more than 90% of cancer-related mortality. Therefore, there is a strong need to prevent metastasis formation or to target existing metastases. It is currently assumed that initiating the epithelial-mesenchymal transition (EMT) process in differentiated cancers may strongly increase the migration potential and invasiveness of cancer cells. Molecular changes occurring during EMT are accompanied by morphological changes, the effect of which is the change of the epithelial phenotype to the mesenchymal one and the acquisition by cancer cells of increased mobility and the ability to invade. After metastasis is formed at a site distant from the primary tumor, cancer cells undergo the reverse process, the mesenchymal-epithelial transition (MET), regaining the epithelial phenotype. This ability of the tumour cell to switch from one state to the other allows permanent adaptations to the demanding conditions of a changing environment and promotes the formation of metastasis. In this review, I discuss two principle types of metastatic progression: phenotypic plasticity involving transient EMTâMET processes and intrinsic genetic alterations keeping cells in an EMT and stemness state. This simplified classification integrates clinically relevant aspects of dormancy, metastatic tropism and therapy resistance, and implies perspectives on treatment strategies against metastasis
Cholesterol is a precursor molecule for vitamin D, bile acids, and steroid hormones. Its oxidized forms, called oxysterols are by-products for synthesis, but also regulate cholesterolâs metabolism through different cell...Cholesterol is a precursor molecule for vitamin D, bile acids, and steroid hormones. Its oxidized forms, called oxysterols are by-products for synthesis, but also regulate cholesterolâs metabolism through different cell receptors. Cholesterol and oxysterols are important cell membrane components. Oxysterols show more biological activity than cholesterol itself, due to their pleiotropic cell effects. Oxysterol, contrary to cholesterol can cross the blood-brain barier and influence the nervous system. The etiology and pathogenesis of cancer can also be influenced by oxysterols. Elevated levels of oxysterol is often observed in many pathological state: diabetes, atherosclerosis, dementia, or endometriosis. Cholesterolâs oxidized forms can regulate immunity by activation or suppression of the immune cell during virus infection and inflammation.
Pierzynowska K, Cyske Z, Gaffke L
… +10 more, Rintz E, Mantej J, Podlacha M, Wiśniewska K, Ĺťabińska M, Sochocka M, Lorenc P, Bielańska P, Giecewicz I, Węgrzyn G
Development of therapies for neurodegenerative diseases, disorders characterized by progressing loss of neurons, is a great challenge for current medicine. Searching for drugs for these diseases is being proceeded in man...Development of therapies for neurodegenerative diseases, disorders characterized by progressing loss of neurons, is a great challenge for current medicine. Searching for drugs for these diseases is being proceeded in many laboratories in the world. To date, several therapeutical strategies have been proposed which, however, are either of insufficient efficacy or at the early preclinical stages. One of the newest concepts is elevated efficiency of degradation of protein aggregates which are causes of 70% of these diseases. Autophagy, i.e. lysosomal degradation of macromolecules, is a process which could be employed in such a strategy Searching for a compound which would not only stimulate autophagy but also reveal safety in a long-term usage and be able to cross the blood-brain-barrier led to studies on one of flavonoids, genistein which occurs at high concentrations in soy. Experiments with this compound indicated its enormous efficiency in removing protein aggregated formed by beta-amyloid, hyperphosphorylated tau protein, and mutant huntingtin. Moreover, using animal models of these diseases, correction of cognitive and motoric symptoms was demonstrated. Considering safety of genistein as well as its ability to crossing the blood-brain-barrier, one may assume that this molecule is a candidate for an effective drug in therapies of not only Alzheimer disease and Huntington disease, but also other disorders caused be protein aggregates. In this article, recent results of studies on the use of genistein in different models of neurodegenerative diseases are summarized, with special emphasis on its autophagy-dependent action.
Citrin deficiency is an inherited metabolic disease caused by biallelic pathogenic variants in the SLC25A13 gene encoding the carrier protein called citrin. There are observed three characteristic clinical and biochemica...Citrin deficiency is an inherited metabolic disease caused by biallelic pathogenic variants in the SLC25A13 gene encoding the carrier protein called citrin. There are observed three characteristic clinical and biochemical age-dependent phenotypes: neonatal intrahepatic cholestasis caused by citrin deficiency, failure to thrive and dyslipidemia caused by citrin deficiency and adult-onset citrullinemia type 2. The paper presents the characteristics of the pathogenesis of citrin deficiency, clinical and biochemical delineation of individual phenotypes, differential diagnosis and treatment of citrin deficiency.