In the last few years, more and more scientists have suggested and confirmed that epigenetic regulators are tightly connected and form a comprehensive network of regulatory pathways and feedback ...loops. This is particularly interesting for a better understanding of processes that occur in the development and progression of various diseases. Appearing on the preclinical stages of diseases, epigenetic aberrations may be prominent biomarkers. Being dynamic and reversible, epigenetic modifications could become targets for a novel option for therapy. Therefore, in this review, we are focusing on histone modifications and ncRNAs, their mutual regulation, role in cellular processes and potential clinical application.
Rheumatoid arthritis (RA) is a systemic autoimmune disease that affects about 1% of the world's population. The etiology of RA remains unknown. It is considered to occur in the presence of genetic ...and environmental factors. An increasing body of evidence pinpoints that epigenetic modifications play an important role in the regulation of RA pathogenesis. Epigenetics causes heritable phenotype changes that are not determined by changes in the DNA sequence. The major epigenetic mechanisms include DNA methylation, histone proteins modifications and changes in gene expression caused by microRNAs and other non-coding RNAs. These modifications are reversible and could be modulated by diet, drugs, and other environmental factors. Specific changes in DNA methylation, histone modifications and abnormal expression of non-coding RNAs associated with RA have already been identified. This review focuses on the role of these multiple epigenetic factors in the pathogenesis and progression of the disease, not only in synovial fibroblasts, immune cells, but also in the peripheral blood of patients with RA, which clearly shows their high diagnostic potential and promising targets for therapy in the future.
According to the Cancer Genome Atlas (TCGA), gastric cancers are classified into four molecular subtypes: Epstein-Barr virus-positive (EBV+), tumors with microsatellite instability (MSI), tumors with ...chromosomal instability (CIN), and genomically stable (GS) tumors. However, the gastric cancer (GC) with chromosomal instability remains insufficiently described and does not have effective markers for molecular and histological verification and diagnosis. The CIN subtype of GC is characterized by chromosomal instability, which is manifested by an increased frequency of aneuploidies and/or structural chromosomal rearrangements in tumor cells. Structural rearrangements in the CIN subtype of GC are not accidental and are commonly detected in chromosomal loci, being abnormal because of specific structural organization. The causes of CIN are still being discussed; however, according to recent data, aberrations in the
gene may cause CIN development or worsen its phenotype. Clinically, patients with the CIN subtype of GC demonstrate poor survival, but receive the maximum benefit from adjuvant chemotherapy. In the review, we consider the molecular mechanisms and possible causes of chromosomal instability in GC, the common rearrangements of chromosomal loci and their impact on the development and clinical course of the disease, as well as the driver genes, their functions, and perspectives on their targeting in the CIN subtype of GC.
Figurate erythema in 11 Eastern European sphynx cats Mendoza‐Kuznetsova, Ekaterina; Lokianskiene, Viktorija; Matise‐VanHoutan, Ilze ...
Veterinary dermatology,
June 2024, 2024-Jun, 2024-06-00, 20240601, Letnik:
35, Številka:
3
Journal Article
Recenzirano
Background
In humans, figurate erythema (FE) represents a heterogenous group of dermatoses with circular or serpiginous erythematous skin lesions; FE has not been reported in cats.
Objectives
To ...report clinical and histological characteristics and outcomes of FE in sphynx cats from Baltic sea‐bordering countries.
Animals
Eleven client‐owned sphynx cats with FE.
Materials and Methods
We recruited cases meeting the following criteria: (i) a sphynx breed, (ii) FE with or without scaling, (iii) a chronic, waxing‐and‐waning course lasting longer than a month and (iv) an absence of other skin diseases.
Results
Of 11 cats, there were seven Donskoys, one Peterbald, one Ukrainian Levkoy and two presumed Canadian sphynxes; all except one were males, and the age of onset was <12 months in eight cats. Skin lesions lasted between 1.2 and 56 months, and they consisted of erythematous plaques with a linear‐to‐serpiginous, annular, gyrate or iris configuration predominating on the trunk and extremities. Scaling was often seen trailing the edge of the centrifugally expanding erythema. All cats were otherwise asymptomatic or mildly pruritic. Dermatophytosis was ruled out by special stains and/or fungal cultures in eight cats. Microscopic lesions revealed focal, mild‐to‐moderate epidermal hyperplasia and hyperkeratosis, minimal‐to‐mild dysplasia and subepidermal collagen smudging. Special stains were negative for dermatophytes. The clinical remission of FE was not achieved with diet changes or medical interventions; yet, a spontaneous, transient, partial or complete improvement occurred in most cats.
Conclusion and Clinical Relevance
This is the first report of FE in sphynx cats from Eastern Europe.
Zusammenfassung
Hintergrund
Beim Menschen repräsentiert das figurative Erythem (FE) eine heterogene Gruppe von Dermatosen mit zirkulären oder geschlängelten erythematösen Hautveränderungen; FE wurde bisher bei Katzen noch nicht beschrieben.
Ziele
Die Beschreibung der klinischen und histologischen Merkmale und das Ergebnis von FE bei Sphynx Katzen aus Ländern, die an das Baltische Meer angrenzen.
Tiere
11 Sphynx Katzen in Privatbesitz mit FE.
Materialien und Methoden
Wir rekrutierten Fälle, die die folgenden Kriterien erfüllten: (i) eine Sphynx Rasse, (ii) FE mit und ohne Schuppenbildung, (iii) eine chronische Krankheit mit einem über mehr als einem Monat dauerndem Krankheitsverlauf, der ein Kommen und Gehen zeigte, und (iv) eine Abwesenheit anderer Hauterkrankungen.
Ergebnisse
Von den 11 Katzen waren sieben Donskoi Katzen, eine Peterbald Katze, eine Ukrainische Levkoy Katze und zwei vermeintlich kanadische Sphinx Katzen; alle außer einer waren männlich, bei acht Katzen lag das Alter beim Beginn der Erkrankung bei < 12 Monaten. Die Haut Veränderungen bestanden über einen Zeitraum von 1,2 bis 56 Monaten und bestanden aus erythematösen Plaques mit einer linearen‐bis‐geschlängelten, ring‐ oder kreisförmigen oder einer Iris‐förmigen Konfiguration, die hauptsächlich am Rumpf und an den Extremitäten auftraten. Eine Schuppenbildung wurde häufig am Rand des sich kreisförmig ausdehnenden Erythems beobachtet. Alle Katzen waren anderweitig asymptomatisch oder wenig juckend. Eine Dermatophytose wurde bei acht Katzen mittels Spezialfärbungen und/oder Pilzkulturen ausgeschlossen. Mikroskopische Veränderungen zeigten eine fokale, mild bis moderate epidermale Hyperplasie und Hyperkeratose, eine minimal bis milde Dysplasie und subepidermales verwaschenes Kollagen. Spezialfärbungen waren negativ für Dermatophyten. Die klinische Remission von FE konnte mit Futterwechsel oder medizinischen Interventionen nicht erzielt werden, allerdings trat bei den meisten Katzen eine spontane, transiente, partielle oder komplette Verbesserung auf.
Schlussfolgerungen und klinische Bedeutung
Es handelt sich hierbei um den ersten Bericht über FE bei Sphynx Katzen aus Osteuropa.
摘要
背景
在人类中，图形红斑(FE)代表一组具有圆形或匍形红斑皮肤病变的异质性皮肤病；猫身上还没有FE的报告。
目的
报告波罗的海沿岸国家的斯芬克斯猫FE的临床、组织学特征和结果。
动物
11只客户拥有的带有FE的斯芬克斯猫。
材料和方法
我们招募了符合以下标准的病例:(i)一个斯芬克斯品种，(ii)有或没有皮屑的FE，(iii)持续一个月以上时好时坏的慢性过程，以及(iv)没有其他皮肤疾病。
结果
在11只猫中，有7只唐斯芬克斯，1只彼得秃猫，1只乌克兰勒夫科伊和2只推测的加拿大斯芬克斯；除1只外，其余均为雄性，8只猫的发病年龄<12个月。皮肤病变持续了1.2至56个月，由红色斑块组成，主要分布在躯干和四肢，呈线状至线状至匍状、回环状、螺旋状或虹膜状。在离心扩散的红斑边缘，经常可以看到皮屑。所有猫均无症状或轻度瘙痒。八只猫的特殊染色和/或真菌培养排除了皮肤癣菌病。镜下病变显示局灶性、轻度至中度表皮增生和角化过度，轻度至轻度发育不良和表皮下胶原结构模糊。特殊染色对皮肤癣菌呈阴性反应。FE的临床缓解并没有通过饮食改变或药物干预来实现，但大多数猫都出现了自发、短暂、部分或完全的改善。
结论和临床相关性
这是首次报道东欧的斯芬克斯猫FE。
Résumé
Contexte
Chez l'homme, l'érythème figuré (EF) représente un groupe hétérogène de dermatoses avec des lésions cutanées érythémateuses circulaires ou serpigineuses ; l'EF n'a pas été rapporté chez le chat.
Objectifs
Décrire les caractéristiques cliniques et histologiques et l’évolutions de l'EF chez les chats sphynx des pays bordant la mer Baltique.
Animaux
11 chats sphynx appartenant à des clients et présentant un EF.
Matériels et méthodes
Nous avons recruté des cas répondant aux critères suivants (i) race sphynx, (ii) FE avec ou sans desquamation, (iii) évolution chronique, en dents de scie, durant plus d'un mois, et (iv) absence d'autres maladies cutanées.
Résultats
Sur 11 chats, il y avait sept Donskoys, un Peterbald, un Levkoy ukrainien et deux sphynx présumés canadiens ; tous sauf un étaient des mâles, et l'âge d'apparition était <12 mois pour huit chats. Les lésions cutanées ont évolué durant 1,2 et 56 mois et consistaient en des plaques érythémateuses de configuration linéaire à serpigineuse, annulaire, gyrée ou en forme d’iris prédominant sur le tronc et les extrémités. Une desquamation est souvent observée sur le bord de la lésion érythèmateuse qui s'étend de façon centrifuge. Tous les chats étaient par ailleurs asymptomatiques ou légèrement prurigineux. La dermatophytose a été exclue par des colorations spéciales et/ou des cultures fongiques chez huit chats. Les lésions microscopiques ont révélé une hyperplasie et une hyperkératose épidermiques focales, légères à modérées, une dysplasie minime à légère et des agglomérats de collagène sous‐épidermiques. Les colorations spéciales étaient négatives pour les dermatophytes. La rémission clinique de la EF n'a pas été obtenue par des changements de régime alimentaire ou des interventions médicales, mais une amélioration spontanée, transitoire, partielle ou complète s'est produite chez la plupart des chats.
Conclusion et pertinence clinique
Il s'agit du premier rapport sur l’EF chez les chats sphynx d'Europe de l'Est.
要約
背景
ヒトでは、Figurate Eerythema:FEは、円形または蛇行性の紅斑性皮膚病変を呈する異種の皮膚疾患群であるが、ネコではFEは報告されていない。
目的
本研究の目的は、バルト海沿岸諸国のスフィンクスにおけるFEの臨床的、組織学的特徴および転帰を報告することであった。
供試動物
FEを発症したオーナー所有スフィンクス11頭。
材料と方法
以下の基準を満たす症例を募集した: (i)スフィンクス種であること、(ii)鱗屑を伴う、または伴わないFEであること、(iii)1ヶ月以上持続する慢性で、一進一退の経過をとること、(iv)他の皮膚疾患がないこと。
結果
11頭中、ドンスコイ7頭、ピーターバルド1頭、ウクライナ産レフコイ1頭、推定カナディアン・スフィンクス2頭で、1頭を除きすべてオスであり、発症年齢は8頭で12ヵ月未満であった。皮膚病変は1.2~56ヵ月持続し、体幹および四肢に線状から蛇状、環状、回旋状、または虹彩状の紅斑性局面で構成された。遠心性に拡大する紅斑の縁にはしばしば鱗屑がみられた。すべての猫に無症状または軽度の掻痒がみられた。皮膚糸状菌症は8頭の猫で特殊染色および/または真菌培養により除外された。顕微鏡病変では、局所的な軽度から中等度の表皮過形成および過角化、ごく軽度から軽度の異形成、表皮下コラーゲンスマッジを認めた。特殊染色では皮膚糸状菌は陰性であった。FEの臨床的寛解は食事の変更や医学的介入では達成されなかったが、ほとんどの猫で自発的、一過性、部分的または完全な改善がみられた。
結論と臨床的意義
本報告は東欧のスフィンクス猫におけるFEの最初の報告であった。
Resumo
Contexto
Em humanos, o eritema figurado (EF) representa um grupo heterogêneo de dermatoses com lesões cutâneas eritematosas circulares ou serpiginosas; o EF não foi ainda relatado em gatos.
Objetivos
Relatar as características clínicas e histológicas e a evolução do EF em gatos sphynx dos países fronteira com o mar Báltico.
Animais
11 gatos sphynx de propriedade do cliente com EF.
Materiais e Métodos
Foram selecionados casos que atendiam aos seguintes critérios: (i) uma raça sphynx, (ii) EF com ou sem descamação, (iii) um curso crônico, intermitente, com duração superior a um mês, e (iv) ausência de outras doenças de pele.
Resultados
Dos 11 gatos, havia sete Donskoys, um Peterbald, um Levkoy ucraniano e duas supostos sphynx canadenses; todos, exceto um, eram machos e a idade de início dos sintomas foi <12 meses em oito gatos. As lesões cutâneas duraram entre 1,2 e 56 meses e consistiam em placas eritematosas com configuração linear a serpiginosa, anular, giratória ou iridiforme predominando no tronco e nas extremidades. A descamação foi frequentemente observada na borda das lesões eritematosas em expansão centrífuga. Todos os gatos eram assintomáticos ou levemente pruriginosos. Dermatofitose foi descartada por colorações especiais e/ou culturas fúngicas em oito gatos. As lesões microscópicas revelaram hiperplasia epidérmica focal leve a moderada e hiperqueratose, displasia mínima a leve e grumos de colágeno subepidérmico. Colorações especiais foram negativas para dermatófitos. A remissão clínica do EF não foi alcançada com mudanças na dieta ou intervenções médicas, mas ocorreu uma melhora espontânea, transitória, parcial ou completa na maioria dos gatos.
Conclusão e Relevância Clínica
Este é o primeiro relato de EF em gatos sphynx da Europa Oriental.
Resumen
Introducción
En humanos, el eritema figurado (EF) representa un grupo heterogéneo de dermatosis con lesiones cutáneas eritematosas circulares o serpiginosas. No se ha descrito EF en gatos.
Objetivos
reportar las características clínicas e histológicas y la progresión de EF en gatos sphynx de los países ribereños del mar Báltico.
Animales
11 gatos sphynx con EF, de propietarios particulares.
Materiales y métodos
seleccionamos casos que cumplían con los siguientes criterios: (i) una raza sphynx, (ii) EF con o sin descamación, (iii) un curso crónico con mejoras y empeoramientos de más de un mes, y (iv) ausencia de otras enfermedades de la piel.
Resultados
de 11 gatos, había siete Donskoy, un Peterbald, un Levkoy ucraniano y dos presuntos sphynx canadienses; todos excepto uno eran machos y la edad de aparición fue <12 meses en ocho gatos. Las lesiones cutáneas duraron entre 1,2 y 56 meses y consistieron en placas eritematosas con configuración lineal a serpiginosa, anular, en circulo o arco, con predominio en el tronco y extremidades. A menudo se observaba de
Rheumatoid arthritis (RA) is the most common inflammatory arthropathy worldwide. Possible manifestations of RA can be represented by a wide variability of symptoms, clinical forms, and course ...options. This multifactorial disease is triggered by a genetic predisposition and environmental factors. Both clinical and genealogical studies have demonstrated disease case accumulation in families. Revealing the impact of candidate gene missense variants on the disease course elucidates understanding of RA molecular pathogenesis. A multivariate genomewide association study (GWAS) based analysis identified the genes and signalling pathways involved in the pathogenesis of the disease. However, these identified RA candidate gene variants only explain 30% of familial disease cases. The genetic causes for a significant proportion of familial RA have not been determined until now. Therefore, it is important to identify RA risk groups in different populations, as well as the possible prognostic value of some genetic variants for disease development, progression, and treatment. Our review has two purposes. First, to summarise the data on RA candidate genes and the increased disease risk associated with these alleles in various populations. Second, to describe how the genetic variants can be used in the selection of drugs for the treatment of RA.
Feline proliferative and necrotising otitis externa (PNOE) is a rare immune-mediated condition, usually self-limiting or responsive to immunosuppressants such as topical tacrolimus. This case report ...describes two cats with refractory PNOE that responded successfully to oclacitinib. One cat also had middle ear involvement and the other cat had extra-auricular dermatitis.
INTEGRAL/IBIS 17-yr hard X-ray all-sky survey Krivonos, Roman A; Sazonov, Sergey Yu; Kuznetsova, Ekaterina A ...
Monthly notices of the Royal Astronomical Society,
03/2022, Letnik:
510, Številka:
4
Journal Article
Recenzirano
Odprti dostop
ABSTRACT
The International Gamma-Ray Astrophysics Laboratory (INTEGRAL), launched in 2002, continues its successful work in observing the sky at energies E > 20 keV. The legacy of the mission already ...includes a large number of discovered or previously poorly studied hard X-ray sources. The growing INTEGRAL archive allows one to conduct an all-sky survey including a number of deep extragalactic fields and the deepest ever hard X-ray survey of the Galaxy. Taking advantage of the data gathered over 17 yr with the IBIS coded-mask telescope of INTEGRAL, we conducted survey of hard X-ray sources, providing flux information from 17 to 290 keV. The catalogue includes 929 objects, 890 of which exceed a detection threshold of 4.5σ and the rest are detected at 4.0σ–4.5σ and belong to known catalogued hard X-ray sources. Among the identified sources of known or suspected nature, 376 are associated with the Galaxy and Magellanic clouds, including 145 low-mass and 115 high-mass X-ray binaries, 79 cataclysmic variables, and 37 of other types; and 440 are extragalactic, including 429 active galactic nuclei (AGNs), 2 ultra-luminous sources, 1 supernova (AT2018cow), and 8 galaxy clusters. 113 sources remain unclassified. 46 objects are detected in the hard X-ray band for the first time. The LogN-LogS distribution of 356 non-blazar AGNs is measured down to a flux of 2 × 10−12 erg s−1 cm−2 and can be described by a power law with a slope of 1.44 ± 0.09 and normalization 8 × 10−3 deg−2 at 10−11 erg s−1 cm−2. The LogN-LogS distribution of unclassified sources indicates that the majority of them are of extragalactic origin.
This article presents the study of the rheological properties and the printability of produced ceramic-polymer filaments using fused deposition method (FDM) 3D printing technology. Powder mixtures ...with an alumina content of 50 to 70 vol.% were fabricated by a wet processing route. A series of rheological experiments of the obtained mixtures were conducted in the temperature range from 200 to 220 °C for the commercial polylactide (PLA) powder and from 200 to 240 °C for ceramic-polymer, which corresponds to the recommended temperatures for 3D printing of commercial PLA filaments. The composition with the maximum content of alumina leads to a powdery material in which the molten polymer is insufficient to measure the rheological properties. In spite of this, the filaments were prepared from all the obtained mixtures with a tabletop single-screw extruder, the diameter and surface profile of which were analyzed. As the ceramic content increased, the diameter and surface roughness of the filaments increased. Therefore, it was only possible to print an object from a filament with the lowest ceramic content. However, the print quality of the 3D printed objects from the fabricated ceramic-polymer filament is worse (imperfect form, defects between layers) compared to the commercial PLA filament. To eliminate such defects in the future, it is necessary to conduct additional research on the development of printing modes and possibly modify the software and components of the 3D printer.
ABSTRACT
In this work, we present the first detailed analysis of the supernova remnant RX J1713.7–3946 in the hard X-ray energy range with the Imager on Board the INTEGRAL Satellite (IBIS) coded-mask ...telescope onboard the INTEGRAL observatory. The shell-type morphology of the entire remnant is mapped in hard X-rays for the first time and significantly detected up to 50 keV. The IBIS sky image of RX J1713.7–3946, accumulated over 14 yr of operations, demonstrates two extended hard X-ray sources. These sources are spatially consistent with north-west and south-west rims of RX J1713.7–3946 and are also clearly visible at energies below 10 keV with XMM–Newton. This points to a single emission mechanism operating in soft and hard X-rays. The INTEGRAL 17–120 keV spectrum of RX J1713.7–3946 is characterized by a power-law continuum with the photon index of Γ ≈ 3 that is significantly softer than Γ ≈ 2 determined by XMM–Newton in the 1–10 keV energy range, suggesting a progressive steepening of the spectrum with the energy.
Somatic mutation profiling in gastric cancer (GC) enables main driver mutations to be identified and their clinical and prognostic value to be evaluated. We investigated 77 tumour samples of GC by ...next-generation sequencing (NGS) with the Ion AmpliSeq Hotspot Panel v2 and a custom panel covering six hereditary gastric cancer predisposition genes (BMPR1A, SMAD4, CDH1, TP53, STK11 and PTEN). Overall, 47 somatic mutations in 14 genes were detected; 22 of these mutations were novel. Mutations were detected most frequently in the CDH1 (13/47) and TP53 (12/47) genes. As expected, somatic CDH1 mutations were positively correlated with distant metastases (p = 0.019) and tumours with signet ring cells (p = 0.043). These findings confirm the association of the CDH1 mutations with diffuse GC type. TP53 mutations were found to be significantly associated with a decrease in overall survival in patients with Lauren diffuse-type tumours (p = 0.0085), T3-T4 tumours (p = 0.037), and stage III-IV tumours (p = 0.013). Our results confirm that the detection of mutations in the main driver genes may have a significant prognostic value for GC patients and provide an independent GC-related set of clinical and molecular genetic data.
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