Circular RNAs (circRNAs) make up approximately 10% of the human transcriptome. CircRNAs belong to the broad group of non-coding RNAs and characteristically are formed by backsplicing into a stable circular loop. Their main role is to regulate transcription through the inhibition of miRNAs' expression, termed miRNA sponging. CircRNAs promote tumorigenesis/lymphomagenesis by competitively binding to miRNAs at miRNA binding sites. In diffuse large B-cell lymphoma (DLBCL), several circRNAs have been identified and their expression is related to both progression and response to therapy. DLBCL is the most prevalent and aggressive subtype of B-cell lymphomas and accounts for about 25% to 30% of all non-Hodgkin lymphomas. DLBCL displays great heterogeneity concerning histopathology, biology, and genetics. Patients who have relapsed or have refractory disease after first-line therapy have a very poor prognosis, demonstrating an important unmet need for new treatment options. As more circRNAs are identified in the future, we will better understand their biological roles and potential use in treating cancer, including DLBCL. For example, circAmotl1 promotes nuclear translocation of MYC and upregulation of translational targets of MYC, thus enhancing lymphomagenesis. Another example is circAPC, which is significantly downregulated in DLBCL and correlates with disease aggressiveness and poor prognosis. CircAPC increases expression of the host gene adenomatous polyposis coli (APC), and in doing so inactivates the canonical Wnt/β-catenin signaling and restrains DLBCL growth. MiRNAs belong to the non-coding regulatory molecules that significantly contribute to lymphomagenesis through their target mRNAs. In DLBCL, among the highly expressed miRNAs, are miR-155-5p and miR-21-5p, which regulate NF-ĸB and PI3K/AKT signaling pathways. The aim of this review is to describe the function and mechanism of regulation of circRNAs on miRNAs' expression in DLBCL. This will help us to better understand the regulatory network of circRNA/miRNA/mRNA, and to propose novel therapeutic targets to treat DLBCL.

• Publication type
• Journal Article MeSH
• Review MeSH

The asymmetrical distribution of the cellular organelles inside the cell is maintained by a group of cell polarity proteins. The maintenance of polarity is one of the vital host defense mechanisms against pathogens, and the loss of it contributes to infection facilitation and cancer progression. Studies have suggested that infection of viruses and bacteria alters cell polarity. Helicobacter pylori and Epstein-Barr virus are group I carcinogens involved in the progression of multiple clinical conditions besides gastric cancer (GC) and Burkitt's lymphoma, respectively. Moreover, the coinfection of both these pathogens contributes to a highly aggressive form of GC. H. pylori and EBV target the host cell polarity complexes for their pathogenesis. H. pylori-associated proteins like CagA, VacA OipA, and urease were shown to imbalance the cellular homeostasis by altering the cell polarity. Similarly, EBV-associated genes LMP1, LMP2A, LMP2B, EBNA3C, and EBNA1 also contribute to altered cell asymmetry. This review summarized all the possible mechanisms involved in cell polarity deformation in H. pylori and EBV-infected epithelial cells. We have also discussed deregulated molecular pathways like NF-κB, TGF-β/SMAD, and β-catenin in H. pylori, EBV, and their coinfection that further modulate PAR, SCRIB, or CRB polarity complexes in epithelial cells.

• MeSH
• Helicobacter pylori * genetics   MeSH
• Epstein-Barr Virus Infections * microbiology   pathology   MeSH
• Helicobacter Infections * microbiology   MeSH
• Coinfection * microbiology   MeSH
• Humans MeSH
• Stomach Neoplasms * genetics   microbiology   pathology   MeSH
• Cell Polarity MeSH
• Viral Proteins MeSH
• Herpesvirus 4, Human genetics   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

Východiska: Incidence karcinomu pankreatu (pancreatic ductal adenocarcinoma – PDAC) má zejména v rozvinutých zemích zvyšující se tendenci. V roce 2021 bylo celosvětově diagnostikováno 496 000 nových případů PDAC. Incidence v ČR je jedna z nejvyšších na světě a za rok 2018 bylo zachyceno 2 332 nových pacientů. Vzhledem k absenci symptomů v časných stadiích je přibližně 50 % pacientů vstupně diagnostikováno se vzdálenými metastázemi. Mortalita je nepatrně nižší než incidence a navzdory výrazným pokrokům v onkologickém výzkumu zůstává PDAC stále fatální diagnózou. Zajímavým přístupem, a to nejen u PDAC, je studium mikrobiomu. Ten je definován jako soubor všech mikroorganizmů (mikrobiota, tedy bakterie, houby, viry archea a protozoa) a jejich genomu v určitém prostředí. Za fyziologických podmínek je střevní mikrobiom v symbióze s osídleným organizmem, a udržuje tak rovnováhu metabolizmu, slizniční imunomodulaci a reguluje proces trávení. Při dysregulaci počtu či funkce střevních mikroorganizmů nastává dysbióza. Ta pak vede ke vzniku metabolických a kardiovaskulárních chorob, k poruchám nervového systému, indukci zánětů střeva či kancerogenezi. Mikrobiota mohou indukovat kancerogenezi několika způsoby, a to zejména vyvoláním zánětlivé odpovědi, snížením schopnosti imunitního systému eliminovat poškozené buňky a v neposlední řadě mohou metabolity mikrobů vést k deregulaci genomu osídleného organizmu. Tato deregulace vede k aktivaci proapoptotických a proproliferativních proteinů. Dosavadní výzkum prokazuje, že na rozvoji PDAC se může podílet právě střevní či orální mikrobiom. Jednou z nejvíce studovaných bakterií je Porphyromonas gingivalis. I u dalších bakterií, jako jsou Fusobacteria, Enterobacter, Klebsiella, Prevotella či Rothia, byla prokázána role při vzniku PDAC. Cíl: Cílem tohoto přehledového článku je poukázat na jeden z možných mechanizmů vzniku PDAC. Ten by mohl být ovlivnitelný, což může znamenat snížení incidence a zlepšení prognózy tohoto agresivního onemocnění.

Background: The incidence of pancreatic cancer (pancreatic ductal adenocarcinoma – PDAC) is increasing, especially in developed countries. In 2021, 496,000 new PDAC cases were diagnosed worldwide. In the Czech Republic, the incidence is one of the highest in the world, with 2,332 new PDAC patients diagnosed in 2018. Due to the absence of symptoms in the early stages, approximately 50% of patients are initially diagnosed with distant metastases. Mortality is slightly lower than the incidence count and, despite significant advances in cancer research, PDAC remains a fatal diagnosis. However, microbiome seems to be an interesting approach, and not only in PDAC patients. Microbiome is defined as the set of all microorganisms (microbiota, i.e. bacteria, fungi, viruses, archaea, and protozoa) and their genome in a certain environment. In a physiological setting, the gut microbiome is in symbiosis with the host organism, maintaining the balance of metabolism, mucosal immunomodulation and regulating the digestion process. When dysregulation of the number or function of intestinal microorganisms occurs, dysbiosis is developed. It may lead to metabolic and cardiovascular diseases, nervous system disorders, induction of intestinal inflammation, or carcinogenesis. Microbiota can induce carcinogenesis in multiple ways, such as by activating an inflammatory response, reducing the immune system‘s ability to eliminate damaged cells, and deregulation of the host genome by microbial metabolites. This deregulation may lead to an activation of pro-apoptotic and pro-proliferative proteins. To date, research shows that the gut or oral microbiome may be involved in the development of PDAC. One of the most studied bacteria is Porphyromonas gingivalis. Other bacteria, such as Fusobacteria, Enterobacter, Klebsiella, Prevotella, and Rothia, have also been shown to play a role in PDAC. Purpose: The aim of this review article is to point out one of the possible mechanisms of cancerogenesis in PDAC patients and its therapeutic influence to reduce the incidence and improve the prognosis of this aggressive disease.

• MeSH
• Carcinoma, Pancreatic Ductal * diagnosis   epidemiology   etiology   microbiology   MeSH
• Dysbiosis complications   microbiology   pathology   MeSH
• Carcinogenesis pathology   MeSH
• Humans MeSH
• Microbiota * MeSH
• Risk Factors MeSH
• Gastrointestinal Microbiome genetics   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH

Mucormycosis is an opportunistic infection affecting mainly immunocompromised hosts. Infection in immunocompetent patients is rare, but may occur typically in trauma or burn victims. We report on a previously healthy young man suffering devastating trauma from an agricultural accident with the subsequent development of a multifocal mucormycosis. Diagnosis was achieved by cultures obtained from non-healing wounds, some of them even covered by a macroscopic mold formation. Specific treatment was initiated soon after the preliminary results indicated mucormycosis. Aggressive surgical therapy, with concomitant use of systemic posaconazole and topical amphotericin B in a combination treatment, led to the elimination of the fungal infection. The remaining deep tissue defects were consequently reconstructed by a muscle flap and skin graft autotransplantation with a good overall outcome, which would not have been possible without the complete remission of mucormycosis. This case study presents the successful use of a combination treatment with systemic posaconazole and topical amphotericin B and underlines the importance of timely and aggressive surgical therapy.

• Publication type
• Case Reports MeSH

T-cell malignancies can be divided into precursor (T-acute lymphoblastic leukemia/lymphoblastic lymphoma, T-ALL/LBL) and mature T-cell neoplasms, which are comprised of 28 different entities. Most of these malignancies are aggressive with rather poor prognosis. Prognosis of relapsed/refractory (R/R) disease is especially dismal, with an expected survival only several months after progression. Targeted therapies, such as antiCD30 immunotoxin brentuximab vedotin, antiCD38 antibody daratumumab, and anti-CCR4 antibody mogamulizumab are effective only in subsets of patients with T-cell neoplasms. T-cells equipped with chimeric antigen receptor (CAR-Ts) are routinely used for treatment of R/R B-cell malignancies, however, there are specific obstacles for their use in T-cell leukemias and lymphomas which are fratricide killing, risk of transfection of malignant cells, and T-cell aplasia. The solution for these problems relies on target antigen selection, CRISPR/Cas9 or TALEN gene editing, posttranslational regulation of CAR-T surface antigen expression, and safety switches. Structural chromosomal changes and global changes in gene expression were observed with gene-edited products. We identified 49 studies of CAR-based therapies registered on www.clinicaltrials.gov. Most of them target CD30 or CD7 antigen. Results are available only for a minority of these studies. In general, clinical responses are above 50% but reported follow-up is very short. Specific toxicities of CAR-based therapies, namely cytokine release syndrome (CRS), seem to be connected with the antigen of interest and source of cells for manufacturing. CRS is more frequent in antiCD7 CAR-T cells than in antiCD30 cells, but it is mild in most patients. More severe CRS was observed after gene-edited allogeneic CAR-T cells. Immune effector cell associated neurotoxicity (ICANS) was mild and infrequent. Graft-versus-host disease (GvHD) after allogeneic CAR-T cells from previous hematopoietic stem cell donor was also observed. Most frequent toxicities, similarly to antiCD19 CAR-T cells, are cytopenias. CAR-based cellular therapy seems feasible and effective for T-cell malignancies, however, the optimal design of CAR-based products is still unknown and long-term follow-up is needed for evaluation of their true potential.

• Publication type
• Journal Article MeSH
• Review MeSH

Introduction: Metastatic cutaneous squamous cell carcinoma (cSCC) is a very rare condition. The lack of definition of an oligometastatic subgroup means that there is no consensus for its treatment, unlike the mucosal head and neck counterpart. Like the latter, the cutaneous form is able to develop bulky tumor masses. When this happens, the classic care approach is just for palliative intent due to a likely unfavorable benefit-risk balance typical of aggressive treatments. Here we proposed a novel radiotherapy (RT) technique to treat bulky metastases from cSCC in the context of an overall limited tumor burden and tried to explain its clinical outcome by the currently available mathematical radiobiological and ad hoc developed models. Methods: We treated a case of facial cSCC with three metastases: two of them by classic stereotactic RT and the other by lattice RT supported by metabolic imaging (18F-FDG PET) due to its excessively large dimensions. For the latter lesion, we compared four treatment plans with different RT techniques in order to define the best approach in terms of normal tissue complication probability (NTCP) and tumor control probability (TCP). Moreover, we developed an ad hoc mathematical radiobiological model that could fit better with the characteristics of heterogeneity of this bulky metastasis for which, indeed, a segmentation of normoxic, hypoxic, and necrotic subvolumes might have been assumed. Results: We observed a clinical complete response in all three disease sites; the bulky metastasis actually regressed more rapidly than the other two treated by stereotactic RT. For the large lesion, NTCP predictions were good for all four different plans but even significantly better for the lattice RT plan. Neither the classic TCP nor the ad hoc developed radiobiological models could be totally adequate to explain the reported outcome. This finding might support a key role of the host immune system. Conclusions: PET-guided lattice RT might be safe and effective for the treatment of bulky lesions from cSCC. There might be some need for complex mathematical radiobiological models that are able to take into account any immune system's role in order to explain the possible mechanisms of the tumor response to radiation and the relevant key points to enhance it.

• Publication type
• Journal Article MeSH

Parodontitida je chronické multifaktoriální onemocnění, jehož výsledkem je progresivní destrukce závěsného aparátu zubů. Z hlediska etiologie je důležitá zejména přítomnost paropatogenů a vnímavost hostitele. Vzhledem k velmi omezeným možnostem ovlivnění vnímavosti hostitele zůstává metodou léčby subgingivální ošetření – mechanické očištění povrchu kořenů zubů od zubního kamene a plaku, často v kombinaci s antibiotiky nebo antiseptiky, aplikovanými lokálně nebo systémově. Při systémové aplikaci antibiotik byly popsány vedlejší účinky (průjmy, zvracení, kovová pachuť), nárůst bakteriální rezistence a možný výskyt alergických reakcí. Navíc v horizontu týdnů až měsíců dochází k rekolonizaci parodontu původními, agresivními bakteriemi, a tudíž jejich použití nemá dlouhodobý efekt. Hledají se proto nové terapeutické postupy pro snížení virulence paropatogenů nebo jejich eliminaci. Do popředí se dostávají teorie zabývající se orálním mikrobiomem a vlivem nedostatku „prospěšných“ bakterií. Ve většině studií se prokazuje pozitivní vliv probiotik z hlediska mikrobiologického, imunologického, ale i klinického. Cílem sdělení je seznámit čtenáře se současnými poznatky a možnostmi využití probiotik při léčbě parodontitidy.

Periodontitis is a chronic multifactorial disease, that results in the progressive destruction of periodontal attachment. Periopathogens and host susceptibility are of great importance in the etiology of the disease. However, there are very few ways of affecting the host ́s susceptibility, therefore deep scaling remains the golden standard of the treatment. Deep scaling is a mechanical debridement of root surfaces, often with a combination of antibiotics and/or antiseptics applied locally or systematically. Antibiotics, when used systematically, may have side effects (diarrhea, nausea, vomiting, metallic taste), an increase of bacterial resistance, and possibly allergic reactions. Moreover, in a matter of weeks or months, a re-colonization of periodontal pockets with aggressive bacteria occurs, so their use does not have a long-term effect. Thus, new therapeutic approaches are being sought to reduce the virulence or eliminate periopathogens. Theories dealing with the oral microbiome and the influence of the lack of ”beneficial“ bacteria became a matter of interest and most of studies have shown a positive microbiological, immunological, and even clinical effect of probiotics. The aim of this review is to familirize the use of probiotics in treatment of periodontitis.

• Keywords
• Lactobacillus reuteri,
• MeSH
• Chronic Periodontitis * classification   physiopathology   therapy   MeSH
• Immunomodulation immunology   MeSH
• Gingival Hemorrhage drug therapy   MeSH
• Humans MeSH
• Periodontal Pocket drug therapy   MeSH
• Probiotics administration & dosage   pharmacology   MeSH
• Dental Plaque drug therapy   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Review MeSH

Cílem tohoto článku je zdůraznit respektování mechanismů odpovědi na inzult při volbě nutriční strategie v časné fázi kritického stavu. Současně článek pojednává o rizicích spojených s časnou agresivní nutriční intervencí, a to jak pro energetický, tak také pro proteinový příjem. Dnes se zdá, že nejoptimálnější volbou nutriční podpory v průběhu prvního týdne pobytu na jednotce intenzivní péče (JIP) je postupné navyšování dávky jak energie, tak i bílkovin. V číselném vyjádření to přibližně znamená vzestup dávky energie o 5 kcal/kg/den a vzestup dávky bílkovin o 0,2 g/kg/den. Platí to ovšem pouze u pacientů přicházejících na JIP s normální hodnotou body mass index, tedy bez malnutrice či obezity. Obě tyto kategorie vyžadují zvláštní pozornost přesahující rozsah tohoto článku.

The aim of this article is to emphasize the importance of taking into account the mechanism of host's response to insult when choosing a nutritional strategy in the early phase of a critical illness. At the same time, the article discusses the risks associated with early aggressive nutritional intervention for both energy and protein intake. Today, it seems that the most optimal choice of nutritional support during the first week of stay in the ICU is a gradual increase in both energy and protein intake. In numerical terms, this means a daily increase in energy dose of approximately 5 kcal/kg/day and a daily increase in protein dose of 0.2 g /kg/day. However, this only applies to patients admitted to the ICU with a normal body mass index, i.e. without malnutrition or without obesity. Both of these categories require special attention beyond the scope of this article.

• Keywords
• překrmování,
• MeSH
• Autophagy MeSH
• Hibernation MeSH
• Critical Illness MeSH
• Humans MeSH
• Nutritional Support * methods   MeSH
• Nutrition Therapy MeSH
• Critical Care * MeSH
• Check Tag
• Humans MeSH
• Publication type
• Review MeSH

Host genetic predispositions to dysregulated immune response can influence the development of the aggressive form of periodontitis (AgP) through susceptibility to oral dysbiosis and subsequent host-microbe interaction. This case-control study aimed to perform a multilocus analysis of functional variants in selected interleukin (IL) genes in patients with the generalized form of AgP in a homogenous population. Twelve polymorphisms in IL-1 gene cluster, IL-6 and its receptor, IL-10, IL-17A, and IL-18 were determined in 91 AgP patients and 210 controls. Analysis of seven selected periodontal bacteria in subgingival sulci/pockets was performed with a commercial DNA-microarray kit in a subgroup of 76 individuals. The pilot in vitro study included stimulation of peripheral blood monocytes (PBMC) from 20 individuals with periodontal bacteria and measurement of IL-10 levels using the Luminex method. Only the unctional polymorphism IL‐10-1087 A/G (rs1800896) and specific IL-10 haplotypes were associated with the development of the disease (P < 0.05, Pcorr > 0.05). Four bacterial species occurred more frequently in AgP than in controls (P < 0.01, Pcorr < 0.05). Elevated IL-10 levels were found in AgP patients, carriers of IL‐10-1087GG genotype, and PBMCs stimulated by periodontal bacteria (P < 0.05, Pcorr > 0.05). We therefore conclude that a combination of genetic predisposition to the altered expression of IL-10 and the presence of specific periodontal bacteria may contribute to Th1/Th2 balance disruption and AgP development.

• MeSH
• Aggressive Periodontitis genetics   immunology   microbiology   MeSH
• Alleles MeSH
• Bacteria genetics   MeSH
• Adult MeSH
• Gene Frequency genetics   MeSH
• Genetic Predisposition to Disease genetics   MeSH
• Genotype MeSH
• Haplotypes genetics   MeSH
• Interleukin-1 genetics   MeSH
• Interleukin-10 genetics   MeSH
• Interleukin-17 genetics   MeSH
• Interleukin-18 genetics   MeSH
• Interleukin-6 genetics   MeSH
• Interleukins genetics   metabolism   MeSH
• Polymorphism, Single Nucleotide genetics   MeSH
• Humans MeSH
• Periodontitis genetics   immunology   MeSH
• Case-Control Studies MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Czech Republic MeSH

Several Botryosphaeriaceae species are known to occur worldwide, causing dieback, canker and fruit rot on various hosts. Surveys conducted in ten commercial citrus orchards in the northern region of Algeria revealed five species of Botryosphaeriaceae belonging to three genera associated with diseased trees. Morphological and cultural characteristics as well as phylogenetic analyses of the internal transcribed spacer (ITS) region and the translation elongation factor 1-alpha (tef1-α) identified Diplodia mutila, Diplodia seriata, Dothiorella viticola, Lasiodiplodia mediterranea and a novel species which is here described as Lasiodiplodia mithidjana sp. nov.. Of these, L. mithidjana (14.1% of the samples) and L. mediterranea (13% of the samples) were the most widespread and abundant species. Pathogenicity tests revealed that L. mediterranea and D. seriata were the most aggressive species on citrus shoots. This study highlights the importance of Botryosphaeriaceae species as agents of canker and dieback of citrus trees in Algeria.

• MeSH
• Ascomycota classification   genetics   pathogenicity   MeSH
• DNA, Fungal genetics   MeSH
• Species Specificity MeSH
• Phylogeny MeSH
• Plant Diseases microbiology   MeSH
• Citrus sinensis microbiology   MeSH
• Virulence MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Geographicals
• Algeria MeSH