Update on cutaneous mesenchymal tumors in the 5th edition of WHO classification of skin tumors with an emphasis on new fusion-associated neoplasms.

The section on mesenchymal tumors in the 5th edition of WHO classification of skin tumors has undergone several changes, the most important of which is the inclusion of newly identified tumor entities, which will be the main focus of this review article. These specifically include three novel cutaneous mesenchymal tumors with melanocytic differentiation, and rearrangements of the CRTC1::TRIM11, ACTIN::MITF, and MITF::CREM genes as well as EWSR1::SMAD3-rearranged fibroblastic tumors, superficial CD34-positive fibroblastic tumors, and NTRK-rearranged spindle cell neoplasms. Some of the other most important changes will be briefly mentioned as well.

Comprehensive clinicopathological, molecular, and methylation analysis of mesenchymal tumors with NTRK and other kinase gene aberrations.

Alterations in kinase genes such as NTRK1/2/3, RET, and BRAF underlie infantile fibrosarcoma (IFS), the emerging entity 'NTRK-rearranged spindle cell neoplasms' included in the latest WHO classification, and a growing set of tumors with overlapping clinical and pathological features. In this study, we conducted a comprehensive clinicopathological and molecular analysis of 22 cases of IFS and other kinase gene-altered spindle cell neoplasms affecting both pediatric and adult patients. Follow-up periods for 16 patients ranged in length from 10 to 130 months (mean 38 months).

Retrotransposons and Telomeres.

Transposable elements (TEs) comprise a significant part of eukaryotic genomes being a major source of genome instability and mutagenesis. Cellular defense systems suppress the TE expansion at all stages of their life cycle. Piwi proteins and Piwi-interacting RNAs (piRNAs) are key elements of the anti-transposon defense system, which control TE activity in metazoan gonads preventing inheritable transpositions and developmental defects.

"If I Were in Nature's Place, I Would Do It Like This..." Life and Hypotheses of Alexey Olovnikov.

In this article, we commemorate the life and scientific journey of the brilliant gerontologist-theorist Alexey Olovnikov (1936-2022). In 1971, he published his famous "marginotomy" hypothesis, in which he predicted the replicative shortening of telomeres and its role as a counter of cell divisions and biological age of an organism. This work put forth several remarkable assumptions, including the existence of telomerase, which were confirmed two decades later.

Telomere Checkpoint in Development and Aging.

The maintenance of genome integrity through generations is largely determined by the stability of telomeres. Increasing evidence suggests that telomere dysfunction may trigger changes in cell fate, independently of telomere length. Telomeric multiple tandem repeats are potentially highly recombinogenic.

MITF::CREM-rearranged tumor: a novel group of cutaneous tumors with melanocytic differentiation.

Cutaneous tumors with melanocytic differentiation represent a broad group of neoplasms of both melanocytic and non-melanocytic origin. Besides traditional members such as clear-cell sarcoma (CCS) and PEComa, the latter group has recently expanded to also include MITF::CREM fusion-associated tumors, but the available data are limited. Herein, we present a third case of this rare neoplasm which occurred in the temporal region in a 1-year-old girl.

The insulator BEAF32 controls the spatial-temporal expression profile of the telomeric retrotransposon TART in the Drosophila germline.

Insulators are architectural elements implicated in the organization of higher-order chromatin structures and transcriptional regulation. However, it is still unknown how insulators contribute to Drosophila telomere maintenance. Although the Drosophila telomeric retrotransposons HeT-A and TART occupy a common genomic niche, they are regulated independently.

Electrochemical Characterization of the Antioxidant Properties of Medicinal Plants and Products: A Review.

Medicinal plants are an important source of bioactive compounds with a wide spectrum of practically useful properties. Various types of antioxidants synthesized in plants are the reasons for their application in medicine, phytotherapy, and aromatherapy. Therefore, reliable, simple, cost-effective, eco-friendly, and rapid methods for the evaluation of antioxidant properties of medicinal plants and products on their basis are required.

Biphenotypic sinonasal sarcoma with PAX3::MAML3 fusion transforming into high-grade rhabdomyosarcoma: report of an emerging rare phenomenon.

We report a case of a 67-year-old male patient with a sinonasal tumor that showed areas of classic biphenotypic sinonasal sarcoma (BSNS) which in some sections sharply transitioned into high-grade rhabdomyosarcoma. Immunohistochemically, the conventional BSNS parts showed S100 protein, SMA, PAX7, and focal MyoD1 expression, whereas desmin and myogenin were negative. In contrast, the cells in high-grade areas expressed desmin, MyoD1, myogenin, and PAX7, while being negative for S100 protein and SMA.

Dysfunction of Lamin B and Physiological Aging Cause Telomere Instability in Drosophila Germline.

Chromatin spatial organization in the nucleus is essential for the genome functioning and regulation of gene activity. The nuclear lamina and lamina-associated proteins, lamins, play a key role in this process. Lamin dysfunction leads to the decompaction and transcriptional activation of heterochromatin, which is associated with the premature aging syndrome.

Evolution of Epigenetic Mechanisms and Signatures.

DNA methylation, histone posttranslational modifications, higher-order chromatin organization and regulation by noncoding RNAs are considered as the basic mechanisms underlying the epigenetic memory [...

Constant-Current Coulometry with Electrogenerated Titrants as a Novel Tool for the Essential Oils Screening Using Total Antioxidant Parameters.

Essential oils are widely used in aromatherapy, medicine, and food industries due to a wide spectrum of bioactivity. Their antioxidant properties can be considered as markers of therapeutic effect and quality. Constant-current coulometry with electrogenerated titrants has been successfully applied for these purposes for the first time.

Whole-Mount RNA FISH Combined with Immunofluorescence for the Analysis of the Telomeric Ribonucleoproteins in the Drosophila Germline.

The RNA fluorescence in situ hybridization (FISH) technique combined with immunostaining is a powerful method to visualize a specific transcript and a protein of interest simultaneously. Although whole-mount RNA FISH is routinely used to determine RNA intracellular localization, a detailed picture of RNA distribution in complex tissues remains a challenge. The main problem is the various permeability of morphologically different cells within a tissue.

Novel insights into the BAP1-inactivated melanocytic tumor.

BAP1-inactivated melanocytic tumor (BIMT) is a group of melanocytic neoplasms with epithelioid cell morphology molecularly characterized by the loss of function of BAP1, a tumor suppressor gene located on chromosome 3p21, and a mutually exclusive mitogenic driver mutation, more commonly BRAF. BIMTs can occur as a sporadic lesion or, less commonly, in the setting of an autosomal dominant cancer susceptibility syndrome caused by a BAP1 germline inactivating mutation. Owing to the frequent identification of remnants of a conventional nevus, BIMTs are currently classified within the group of combined melanocytic nevi.

Loss of telomere silencing is accompanied by dysfunction of Polo kinase and centrosomes during Drosophila oogenesis and early development.

Telomeres are nucleoprotein complexes that protect the ends of eukaryotic linear chromosomes from degradation and fusions. Telomere dysfunction leads to cell growth arrest, oncogenesis, and premature aging. Telomeric RNAs have been found in all studied species; however, their functions and biogenesis are not clearly understood.

Human Gut Microbiome Response to Short-Term -Based Probiotic Treatment.

Gut microbiota is believed to play a crucial role in modulating obesity in humans, and probiotics affecting gut microbiota can alleviate some of the obesity-related health complications. The study was aimed to investigate changes in the composition of the gut microbiome in obese humans due to short-term (2 weeks) treatment of obese patients with a probiotic preparation containing . Faecal microbiome diversity was studied using the 16S amplicon sequencing by Illumina MiSeq.

EWSR1-PATZ1-rearranged sarcoma: a report of nine cases of spindle and round cell neoplasms with predilection for thoracoabdominal soft tissues and frequent expression of neural and skeletal muscle markers.

The knowledge of clinical features and, particularly, histopathological spectrum of EWSR1-PATZ1-rearranged spindle and round cell sarcomas (EPS) remains limited. For this reason, we report the largest clinicopathological study of EPS to date. Nine cases were collected, consisting of four males and five females ranging in age from 10 to 81 years (average: 49 years).

Epigenetic Requirements for Triggering Heterochromatinization and Piwi-Interacting RNA Production from Transgenes in the Germline.

Transgenes containing a fragment of the retrotransposon represent a powerful model of piRNA cluster formation in the germline. We revealed that the same transgenes located at different genomic loci form piRNA clusters with various capacity of small RNA production. Transgenic piRNA clusters are not established in piRNA pathway mutants.

Inflammatory leiomyosarcoma shows frequent co-expression of smooth and skeletal muscle markers supporting a primitive myogenic phenotype: a report of 9 cases with a proposal for reclassification as low-grade inflammatory myogenic tumor.

Inflammatory leiomyosarcoma (ILMS) is a very rare soft tissue tumor that usually follows an indolent clinical course, but long-term follow-up studies are lacking. Recent publications primarily focused on its genetic profile characterized by a near haploid genome. One study also showed these tumors to have upregulation of genes known to be crucial for skeletal muscle differentiation.

Nuclear Ccr4-Not mediates the degradation of telomeric and transposon transcripts at chromatin in the Drosophila germline.

Ccr4-Not is a highly conserved complex involved in cotranscriptional RNA surveillance pathways in yeast. In Drosophila, Ccr4-Not is linked to the translational repression of miRNA targets and the posttranscriptional control of maternal mRNAs during oogenesis and embryonic development. Here, we describe a new role for the Ccr4-Not complex in nuclear RNA metabolism in the Drosophila germline.

Nature and Functions of Telomeric Transcripts.

Telomeres are complex and dynamic structures whose functions and composition change during the cell cycle and development. Telomeric transcripts are essential components of telomeres. Transcription regulation and cellular levels of telomeric RNAs are closely associated with the control of telomere length, formation of telomeric chromatin, telomere replication, and regulation of non-telomeric gene transcription, which indicates a critical regulatory role of telomeric RNAs in telomere protection and transmission of signals about the state of telomeres to cellular genes.

The Integrity of piRNA Clusters is Abolished by Insulators in the Germline.

Piwi-interacting RNAs (piRNAs) control transposable element (TE) activity in the germline. piRNAs are produced from single-stranded precursors transcribed from distinct genomic loci, enriched by TE fragments and termed piRNA clusters. The specific chromatin organization and transcriptional regulation of germline-specific piRNA clusters ensure transcription and processing of piRNA precursors.