Morphological Anomalies Research Articles

Lead exposure affects cephalic morphogenesis and neural crest cells in Gallus gallus embryo

The morphogenesis of the head of vertebrates is a process that involves rapid growth and dynamic movements of various cell populations, including the neural crest cells (NCC). These pluripotent cells generated during neurulation have high proliferative and migratory capacity but xenobiotic agents can affect these migratory periods and cause congenital malformations. Lead (Pb) is the most common toxic metal in the environment and a potent teratogen that can affect growth and induce malformations. Despite the known toxic effects of Pb, there is a gap in knowledge about the impact of realistic concentrations of Pb at critical periods of early development. Here, we evaluated mortality, embryonic morphology, NCC migration, and the amount of Pb deposition in chicken embryos after 3 to 4 days of exposure. One of the most interesting observations in this study is that only about 34% of the injected Pb was present in the embryos after 4 days. We observed that exposure to Pb, even under low concentrations, increased mortality and the occurrence of malformations during embryonic development, especially in the cephalic region (CR). Although Pb was found widely distributed in the CR, no relation between its presence and the migration routes of cephalic NCC was observed. But the number of NCC and their migratory distance were reduced. These changes are consistent and explain the morphological anomalies described in this study, which also correlates with the morphofunctional abnormalities reported in the literature. Therefore, this study highlights the concern of exposure to low concentrations of this metal.

Studying the Social History of a Russian Microregion, Based on Historical Maps and Aerial Survey

This study focused on a Russian agrarian microregion (12.5 km2) situated in a forest steppe area (in Tambov Oblast) during the 18th–19th centuries. The research illuminates the mechanisms, patterns, and impact that the environment has on social processes, and vice versa — the human impact on the environment (and particularly on landscape). The authors created a geographic information system which they used to compare the results of aerial survey and satellite imagery, with historical maps and other sources, including archival documents. Morphological anomalies were identified on an orthophotomap, and then interpreted. The conclusions of the research concern the nature of interaction between the agrarian society and the environment. Settlement in the plains of the forest steppe was heavily dependent on the water regime, which directly affected the condition and dynamics of communication routes and economic infrastructure. The vanished settlement found in this study is an example of such an effect: it grew up along a road and was abandoned when the areas through which the road ran were waterlogged. Plain rivers can alter the surrounding landscape quite drastically over relatively short historical periods, and are themselves subject to anthropogenic influence. Changes in living conditions and economic management led to variability in settlement patterns and land use. This can be seen especially well in the lowland, where such schemes were predominantly temporary. The processing of Earth remote sensing data makes it possible to fill gaps in sources and discover new evidence of the past.

A true accessory placental lobe: Two case reports of a novel morphological placental anomaly, distinct from succenturiate and bilobed placenta

Introduction: The placenta is a complex organ, originating from both fetal and maternal tissues. Morphological placental anomalies are rare but can result in significant morbidity and mortality for both the fetus and mother. The use of ultrasound imaging to detect these anomalies has led to improved outcomes; however, the use of ultrasound technology for non-medical purposes, such as “keepsake” imaging has proved more controversial.

A Rare Case Report of Hypoplasia of Liver Lobe with Ectopia of Gall Bladder- Is Small Liver Lobe Always Pathological?

Hypoplasia of right lobe of the liver with secondary ectopia of gall bladder is one of the rare morphological developmental anomalies of liver. Frequently, it is also associated with other hepatobiliary anomalies. Patients with such anomalies are more prone to surgical complications due to altered anatomical positions and are also at risk to develop cholecystitis, gall stones, and portal hypertension. The knowledge of such liver anomalies is important for radiologists to avoid surgical and medical pitfalls. Here, the authors report a rare case of hypoplasia of right lobe of liver in a 74-year-old female patient who had no clinical features of liver or biliary disease and with normal liver function test. It was incidentally detected in her Computed Tomography (CT) pulmonary angiogram and further confirmed in Ultrasound (US) and Magnetic Resonance Imaging (MRI)

A Review of the Anomalies in Directed Energy Deposition (DED) Processes & Potential Solutions - Part Quality & Defects

Directed Energy Deposition (DED) processes allow additive manufacturing and repair of metallic components with generatively-designed complex geometries, and excellent compositional control. However, its applicability and adoption have been limited when compared to powder bed fusion (PBF) because several issues and anomalies innate to the process are yet to be suitably understood and resolved. This work catalogues and delineates these anomalies in the DED process along with their causes and solutions, based on a state-of-the-art literature review. This work also serves to enumerate and associate the underlying causes to the detrimental effects which manifest as undesirable part/process outcomes. These DED-specific anomalies are categorized under groups related to the part, process, material, productivity, safety, repair, and composition; this paper will specifically report on the first group - part quality and defects, which is further sub-classified into geometrical, morphological and microstructural anomalies. Altogether, this primer acts as a guide to best prepare for and mitigate the problems that are encountered in DED, and also to lay the groundwork to inspire novel solutions to further advance DED into mainstream manufacturing.

Morphological anomalies in the body structure of Hoplopleura spp. (Anoplura: Hoplopleuridae).

Morphological anomalies in sucking lice (Phthiraptera: Anoplura) have been discussed sporadically, mainly when the changes were considerable, such as in the structure of the reproductive organs or pleural plates, and have concerned the most commonly-studied species. An analysis of 376 specimens from three species of the genus Hoplopleura (H. acanthopus, H. affinis, H. edentula) identified 13 individuals with changes in the number and size of the setae on the sternal plates of the abdomen and irregularities in the structure of the plate itself (3.5% of the collection). The above anomalies do not invalidate the taxonomic decisions.

Laparoskopska holecistektomija kod situs inversus totalis anomalije - prikaz slučaja

Situs inversus totalis represents a rare autosomal recessive morphological anomaly of the internal viscera, equally affecting both genders. The genetic defect occurs in the 2nd week of embryonic life, when a 270-degree clockwise rotation of the primitive digestive tube occurs. The incidence of calculosis of gallbladder in patients with situs inversus is the same as in the general population. A 61-year-old female patient with a history of four episodes of colicky, left hypochondrium and epigastric pain, without fever and jaundice, was admitted for elective laparoscopic cholecystectomy. CT of abdomen confirmed situs inversus totalis that was previously known to the patient. The patient was positioned in supine position and a mirror image configuration of the operating room was obtained, with surgeon and scrub nurse on the right side and assistant on the left side of the patient. Four trocars were introduced mirroring the standard position of the 5 mm trocars. During the dissection, second assistant was introduced for the laparoscope, due to the surgeon's limited motor skills in his left hand for delicate dissection, rendering him inapt to perform precise and safe dissection. The total operating time amounted to 110 minutes, which is three times longer than the standard operating time at our institution. The most critical point of the operation in constellation of situs inversus totalis is applying the clips, which requires precision and strength in the same moment. In the available literature, 40 open cholecystectomies before introduction of laparoscopy and 92 laparoscopic cholecystectomies were reported. To our knowledge, this is the first and the only reported laparoscopic cholecystectomy for situs inversus in North Macedonia.

TWO Caranx caninus (CARANGIDAE, PERCIFORMES) SPECIMENS WITH PUG-HEADED, EXOPHTHALMOS, OPERCLE, AND ANAL FIN ABNORMALITIES; FIRST RECORD FOR THE EASTERN PACIFIC

The Pacific crevalle jack, Caranx caninus Günther, 1867, is a marine pelagic migratory fish species that usually inhabit shallow coastal water, including brackish and estuarine areas. The “pug-headed” abnormality in teleost fishes is characterized by an abnormal skeletal formation of the head, affected by an anteroposterior compression of the upper jaw, resulting in an abnormally shorter upper jaw concerning its lower jaw. In October 2016, an artisanal fisherman from Puerto Chale (Eastern Pacific, Mexico) captured a shoal of Pacific crevalle jack, where two of them presented morphological anomalies of pug-head, exophthalmos, opercle and anal fin. Both specimens’ size and weight were 69.9 and 59.3 cm fork length and 3200 and 2550 g, respectively. One of the individuals was a six-year-old female. A list of 58 cases of pug-headed marine fishes worldwide is provided and reviewed in this article. This study is the first report for the Eastern Pacific and also for wild specimens of Carangidae species. The causes of this abnormality remain uncertain and the main hypotheses were reviewed in this study. However, factors such as temperature, nutrition, salinity, oxygen dissolved, pressure, unspecified pollutants are not discarded. More studies in the future, including new techniques, must be done to clarify the causes of this abnormality.

Hereditary burden in poultry of different species of the Ukrainian gene pool

The relevance of the study is conditioned by the need to continually conduct autopsy analysis of dead embryos as an integral part of genetic monitoring of harmful mutations, which may reduce the level of genetic burden in the gene pool of poultry. The study was conducted on poultry of different species of the Ukrainian gene pool: chickens of meat and egg area of productivity, turkeys of the original family lines of the Kharkiv crossing. The purpose of the study was to determine the spectrum and frequency of manifestation of hereditary genetic defects in the development of embryos in land birds of different species, to establish the level of genetic burden. The spectrum and frequency of morphological and anatomical hereditary defects of chicken and turkey embryos were established during pathological and anatomical examination of incubation waste. Visual examination of dead embryos allowed identifying morphological abnormalities in the structure of the skeleton, as well as various disproportions of its individual parts. In chickens of subpopulations with black-striped and white plumage, among birds of all studied groups, the widest range of morphological abnormalities of embryo development was discovered. In meat and egg hens with golden plumage, three anomalies with the same frequency of manifestation of 33.3% were found among the examined dead embryos. Only 1 anomaly “exencephaly” was found in birds with mottled plumage. Two cases of double mutation were found in birds with silver plumage among the examined dead embryos. The level of genetic burden in the studied subpopulations of meat and egg chickens was in the range of 3.45-8.72%. In birds with white and silver plumage, this figure was higher than the maximum allowable value, therefore it is necessary to carry out selection measures to eliminate lethal genes from these populations of chickens. In turkeys of the paternal line 5 and maternal line 6 of the Kharkiv crossing, 2 morphological anomalies of embryo development were found among the examined dead embryos. The level of genetic burden in turkeys of related forms is low – 1.60-1.89%, which does not exceed the maximum allowable value (8.0%). This indicates a low share in the heredity of the used offspring of hidden carriers of “defective” genes. At this stage, the preservation of the gene pool of birds is not threatening for its further breeding

Morphological identification of pathogenic agents associated with Tabebuia rosea (Bignoniaceae) in nursery stage in morelia (Risaralda)

Introducción. Las susceptibilidades de las plantaciones al ataque de organismos dañinos pueden ocasionar efectos nocivos para su desarrollo, cuando se considera que el nivel de daños ocasionado no se puede tolerar, es indispensable determinar acertadamente la naturaleza del agente causal, sea éste tipo biótico o abiótico; la acertada determinación del agente de un problema fitosanitario en un vivero o plantaciones forestale, se fundamenta en un análisis detallado de los factores que la pueden estar afectando. Tabebuia rosea o Guayacán rosado es una especie forestal nativa de amplia aceptación en el mercado, que presenta durante su etapa de vivero, limitantes en las fases de germinación, emergencia y sobrevivencia, por lo anterior el objetivo de esta investigación era la de Identificar morfológicamente los posibles agentes patógenos asociados a Tabebuia rosea en etapa de vivero y comprobar su patogenicidad. Metodología. Se tomaron plántulas de vivero, las cuales se les realizo un análisis de los signos y los síntomas para el aislamiento y siembra de zonas afectadas en agar papa dextrosa. En el cultivo mixto se identificó los posibles agentes patógenos, los cuales fueron sembrados para obtener cultivos puros, y utilizados en la prueba de patogenicidad, para la inoculación de las estructuras sanas (hojas, peciolos y tallos) y su respectivo control. Resultados. Se identificaron tres géneros de hongos Colletotrichum, Mucor, y Candida, y un género de nematodo denominado Meloidogyne. La prueba de patogenicidad para Colletotrichum y Candida mostraron relaciones significativas en el proceso de infección principalmente en estructuras foliares. Se concluye en este trabajo dos nuevos posibles géneros patógenos para Tabebuia rosea evidenciados en la prueba de patogenicidad. Y se corrobora que el género Meloidogyne es un patógeno severo en el guayacán rosado que ocasiona anomalías morfológicas en la raíz; cabe resaltar que es el primer reporte para el departamento de Risaralda

Planktonic Invertebrates in the Assessment of Long-Term Change in Water Quality of the Sorbulak Wastewater Disposal System (Kazakhstan)

The multicomponent composition of wastewater makes it challenging to assess its quality objectively, but the last one is a prerequisite for the safe re-use of wastewater. The solution to this problem should be aimed at finding criteria that make it possible to increase the objectivity of assessing the water quality of reservoirs with multicomponent pollution. This work analyzes the water quality of the Sorbulak wastewater disposal system in the summer of 2017, based on chemical variables and zooplankton structure and assess the long-term changes in the water quality of Sorbulak. According to the Kruskal–Wallis test, in 2017, the differences between the studied water bodies in the content of nutrients and heavy metals were mostly insignificant. From 2000–2002 to 2017, nitrate, nitrite nitrogen, and heavy metals in Sorbulak significantly decreased. Zooplankton communities consisted of a relatively small number of eurybiontic species resistant to environmental factors. The variability of the quantitative variables of zooplankton was associated with the nutrients. Males dominated the population of the cyclopoid copepods Acanthocyclops trajani. In 2000–2002 individuals with morphological anomalies were found in cyclopoid copepods populations, but were absent in 2017. The appearance of individuals with morphological anomalies was associated with copper or lead. The chemical data and structure of zooplankton communities indicated that the toxic pollution of Sorbulak decreased by 2017 compared to 2000–2002. Our results demonstrate that the structural variables of zooplankton communities could be successfully used to assess the water quality of water bodies with mixed pollution. We recommend using not only the traditional set of biological variables (abundance, biomass, diversity indices, and the average mass of an individual), but also data on the structure of species dominance, the sex structure of copepod populations, and the presence of individuals with morphological anomalies for monitoring of water bodies with mixed pollution.

Evidence of mutagenic and lethal effects of herbicides on Amazonian frogs

ABSTRACT Amphibians are excellent bioindicators because they are sensitive to chemical pollution and can indicate ecosystem changes due to the presence of or exposure to chemical compounds. Here we report evidence of the impact of herbicides, including glyphosate, on amphibians in a locality in the central Brazilian Amazon and compare it with data from other biomes in Brazil. We observed malformations in three species of Leptodactylus and local extinctions of Scinax ruber and Rhinella marina from reproductive sites close to an area where herbicides had been applied. The observations in the Amazon are similar to reports from Brazil’s Atlantic forest on morphological anomalies and mortality in amphibians exposed to herbicides. We warn of the threat of expanding crops for the production of biofuels in the Amazon due to their cultivation being associated with agrochemicals, including glyphosate, posing a threat to the biodiversity of the Amazon biome.

Amniocele after laparoscopic myomectomy: is expectant management acceptable?

Amniocele after laparoscopic myomectomy: is expectant management acceptable?

Review of noise removal techniques in ECG signals

An electrocardiogram (ECG) records the electrical signal from the heart to check for different heart conditions, but it is susceptible to noises. ECG signal denoising is a major pre-processing step which attenuates the noises and accentuates the typical waves in ECG signals. Researchers over time have proposed numerous methods to correctly detect morphological anomalies. This study discusses the workflow, and design principles followed by these methods, and classify the state-of-the-art methods into different categories for mutual comparison, and development of modern methods to denoise ECG. The performance of these methods is analysed on some benchmark metrics, viz., root-mean-square error, percentage-root-mean-square difference, and signal-to-noise ratio improvement, thus comparing various ECG denoising techniques on MIT-BIH databases, PTB, QT, and other databases. It is observed that Wavelet-VBE, EMD-MAF, GAN2, GSSSA, new MP-EKF, DLSR, and AKF are most suitable for additive white Gaussian noise removal. For muscle artefacts removal, GAN1, new MP-EKF, DLSR, and AKF perform comparatively well. For base-line wander, and electrode motion artefacts removal, GAN1 is the best denoising option. For power-line interference removal, DLSR and EWT perform well. Finally, FCN-based DAE, DWT (Sym6) soft, MABWT (soft), CPSD sparsity, and UWT are promising ECG denoising methods for composite noise removal.

PSIII-4 Asthenozoospermia in geomagnetic activity

Abstract Reproductive qualities depend on a complex of biotic and abiotic factors. The ejaculate of bulls is characterized by morphological heterogeneity. Pathologies in the structure of each segment or several segments simultaneously may occur under the influence of biotic and abiotic factors. The aim of the study was to study the influence of geomagnetic storm on the occurrence of asthenozoospermia in freshly collected bull sperm. Monitoring of geomagnetic activity in the region of the study was carried out according to the Institute of terrestrial magnetism, ionosphere and radio wave propagation. N. V. Pushkova of the Russian Academy of Sciences.Sperm quality assessment was carried out using the software “Argus-CASA.” A Mackler’s camera was used to assess mobility and concentration. Statistical analysis of the results of the study was carried out using IBM SPSS Statistics 23.0. The slides were visualized using a Nikon Eclipse Ni-U microscope and a Nikon DS-Qi2 camera. A geomagnetic storm with a K-index ≥ 5.0 was recorded four times in the monitoring region during the study period. During the period when the geomagnetic situation was normal (K = 1,0 1.0), the content of sperm with progressive movement (PR – progressive-mobile) was 87±2.3%, it varied from 82% to 91%. The content of sperm with flagella pathology was 5.74±0.12%. With an increase in geomagnetic activity to K-index ≥ 5.0, the content of sperm with non – progressive movement (NP-non-progressive-motile) increased to 14.2% and motionless sperm to 27.8% (IM-motionless). The content of motionless sperm at some individuals was 38%. Cells with multiple morphological anomalies accounted for 34% at some bulls. Asthenozoospermia in the period of geomagnetic activity is accompanied by an increase in the number of cells with flagella pathology, including multiple morphological anomalies. The study was supported by RFBR, project №. 18-016-00128 А

The assessment of cadmium nitrate effect on morphological and cytogenetic indices of spring barley (Hordeum vulgare) seedlings

The influence of different concentrations of the heavy metal (Cd) − Cd(NO3)2 − on seedlings of four cultivars of the spring barley was studied (the length of shoots and roots, the percentage of germinated seeds and strong seedlings were estimated). The topic of this work is investigation of effects of cadmium nitrate doses range on seedlings of several cultivars of spring barley of different geographical origin and searching of the Cd critical dose. For realization of these goals, an analysis of visible changes of the plants morphology and cytogenetical analysis (for searching of the discovered morphological changes causes) are suitable. Cadmium enters plants organism by the root path, and with this, morphological and cytogenetic effects in the seedlings roots have the highest value. Suppression of growth processes was described with an increase in the dose of Cd, and the appearance of morphological anomalies of seedlings was noted. Thus, average shoots length was decreased twice on the Cd2+ concentrations range 0.15–0.4 mg mL−1; at the range from 0.4 to 0.7 mg mL−1, this index was maintained on the plateau, and at doses higher than 1 mg mL−1, a total suppression of shoots development was noted. Cytogenetic analysis was performed to clarify the reasons for the formation of these reactions. The increase in the yield of cytogenetic disorders was revealed with increasing cadmium concentration, and the blockage of proliferation in the late stages of mitosis was marked. High frequencies of multipolar mitoses, anomalous dividing of chromosomes, chromosome agglutinations and pathological anaphases have been indicated. At maximum dose, the frequency of cells with cytogenetic anomalies was 19 times higher than at control variant. Doses of Cd, which can be considered as not so harmful for plants, were estimated as 0.1–0.2 mg mL−1. 0.3–0.7 mg mL−1 caused significant inhibition of growth processes, while doses higher than 1 mg mL-1 can be considered as conditionally lethal ones. It is shown that the barley cultivars have a significant differentiation in their resistance to cadmium, and the probable causes of the formation of observed effects were considered on the basis of literature data. With this, the Cd dose of 0.35 mg mL−1 can be considered as critical and can be used for searching of barley cultivars, which have the high tolerance to Cd influence. In perspective, such cultivars can be used for agricultural production in the territories with the high rates of Cd soil pollution.

Alpha-lipoic acid ameliorates cytarabine-induced developmental anomalies in rat fetus.

Cytarabine (Ara-C) is a nucleoside analogue used in the treatment of cancers and viral infections. It has teratogenic potential and causes a variety of birth defects in fetuses. Alpha-lipoic acid (ALA) is a natural antioxidant offers protection against the developmental toxicity induced by drug- or toxicant-exposure or pathological conditions. This study was aimed at evaluating the protective effect of ALA against Ara-C induced developmental toxicity in rat fetus. Pregnant rats divided into five groups and received normal saline, ALA200 mg/kg, Ara-C12.5 mg/kg, Ara-C25 mg/kg and, Ara-C25 mg/kg plus ALA200 mg/kg respectively from gestational day (GD) 8 to GD14 and sacrificed on GD21. Ara-C treatment led to a significant and dose-dependent decrease in food intake, weight gain, placental weight, and an increase in oxidative stress in pregnant rats. Further, the in-utero exposure to Ara-C led to an increase in fetal mortality, resorptions, oxidative stress, external morphological anomalies and limb abnormalities, and impaired ossification. Co-administration of ALA resulted in amelioration of the footprints of Ara-C induced toxicity in pregnant rats as well as the fetus. These findings indicate that the ALA supplementation offers protection against developmental toxicity caused by Ara-C prenatal exposure in rats.

Algicidal Activity of Cyperus rotundus Aqueous Extracts Reflected by Photosynthetic Efficiency and Cell Integrity of Harmful Algae Phaeocystis globosa

Phaeocystis globosa is regarded as a notoriously harmful algal bloom species. Suppressing harmful algae using algicidal substances extracted from plants is considered an effective method. The physiological and biochemical processes of P. globosa were explored by exposure to different concentrations of aqueous extracts of Cyperus rotundus. All treatments indicated various inhibitory effects on the algal growth compared to the control samples without adding extracts. At 48 h, the 4, 8, and 16 mg/mL treatment groups showed a significant inhibitory effect, consistent with a decrease in the chlorophyll-a content and photosynthetic efficiency. The images of the transmission electron microscope (TEM) further confirmed that a subset of the cells in the treatment groups exhibited morphological anomalies. The algicidal active substances were mainly identified as phenolic acids containing maximal content of quinic acid in aqueous extracts according to the results of ultra-high-performance liquid chromatography-tandem time-of-flight mass spectrometer (UPLC-HRMS). The 50% anti-algal effect concentration of quinic acid was 22 mg/L at 96 h (EC50–96h). Thus, the phenolic acids might be considered as major inhibitors of the growth of P. globosa. These results demonstrated that the aqueous extracts of C. rotundus could potentially control the growth of P. globosa.

Defining Features of Hand Anomalies in Severe Thumb Hypoplasia: A Classification Modification

Purpose To investigate morphologic hand anomalies in children with severe but unclassifiable forms of thumb hypoplasia and radial-sided hand deficiency. Methods We identified 15 extremities in 13 patients with severe thumb hypoplasia and associated absent radial-sided digits through the Congenital Upper Limb Differences registry. All patients had forearm involvement. Medical records, clinical photographs, and radiographs were evaluated. Radial longitudinal deficiency (RLD) and thumb hypoplasia were classified according to the Bayne and Klug classification and modified Blauth classification, respectively. Unusual or defining associated hand characteristics were identified and categorized. Results The most common type of forearm abnormality was absence of the radius (Bayne and Klug type IV), which was present in 10 extremities in the cohort. All 15 extremities had absent thumbs with loss of additional digits. In 6 patients, RLD was part of a syndrome (46%). Conclusions Severe forms of thumb hypoplasia in RLD are uncommon. We propose a further modification of the Blauth classification of thumb hypoplasia, type VI, for improved communication regarding this severe type of radial deficiency involving the hand. Type of study/level of evidence Diagnostic IV. To investigate morphologic hand anomalies in children with severe but unclassifiable forms of thumb hypoplasia and radial-sided hand deficiency. We identified 15 extremities in 13 patients with severe thumb hypoplasia and associated absent radial-sided digits through the Congenital Upper Limb Differences registry. All patients had forearm involvement. Medical records, clinical photographs, and radiographs were evaluated. Radial longitudinal deficiency (RLD) and thumb hypoplasia were classified according to the Bayne and Klug classification and modified Blauth classification, respectively. Unusual or defining associated hand characteristics were identified and categorized. The most common type of forearm abnormality was absence of the radius (Bayne and Klug type IV), which was present in 10 extremities in the cohort. All 15 extremities had absent thumbs with loss of additional digits. In 6 patients, RLD was part of a syndrome (46%). Severe forms of thumb hypoplasia in RLD are uncommon. We propose a further modification of the Blauth classification of thumb hypoplasia, type VI, for improved communication regarding this severe type of radial deficiency involving the hand.

Accelerated FASTK mRNA degradation induced by oxidative stress is responsible for the destroyed myocardial mitochondrial gene expression and respiratory function in alcoholic cardiomyopathy

Chronic alcoholism disrupts mitochondrial function and often results in alcoholic cardiomyopathy (ACM). Fas-activated serine/threonine kinase (FASTK) is newly recognized as a key post-transcriptional regulator of mitochondrial gene expression. However, the modulatory role of FASTK in cardiovascular pathophysiology remains totally unknown. In experimental ACM models, cardiac FASTK expression markedly declined. Ethanol directly suppressed FASTK expression at post-transcriptional level through NADPH oxidase-derived reactive oxygen species (ROS). Ethanol destabilized FASTK mRNA 3′-untranslated region (3′-UTR) and accelerated its decay, which was blocked by the clearance of ROS. Regnase-1 (Reg1), a ribonuclease regulating mRNA stability, was induced by ROS in ethanol-stimulated cardiomyocytes. Reg1 directly bound to FASTK mRNA 3′-UTR and promoted its degradation, whereas silencing of Reg1 reversed ethanol-induced FASTK downregulation. Compared to wild type control, alcohol-related myocardial morphological (hypertrophy, fibrosis and cardiomyocyte apoptosis) and functional (reduced ejection fraction and compromised cardiomyocyte contraction) anomalies were worsened in FASTK deficient mice. Mechanistically, FASTK ablation repressed NADH dehydrogenase subunit 6 (MTND6, a mitochondrial gene encoding a subunit of complex I) mRNA production and reduced complex I-supported respiration. Importantly, cardiomyocyte-specific upregulation of FASTK through intra-cardiac AAV9-cTNT injection mitigated myocardial mitochondrial dysfunction and restrained ACM progression. In vitro study showed that overexpression of FASTK ameliorated ethanol-induced MTND6 mRNA downregulation, complex I inactivation, and cardiomyocyte death, whereas these beneficial effects were counteracted by rotenone, a complex I inhibitor. Collectively, ROS-accelerated FASTK mRNA degradation via Reg1 underlies chronic ethanol ingestion-associated mitochondrial dysfunction and cardiomyopathy. Restoration of FASTK expression through genetic approaches might be a promising therapeutic strategy for ACM.