Biochemical Genetics最新文献

The objective of this study is to investigate the the relationships between HLA-G gene variants and sHLA-G with susceptibility to SARS-CoV-2 infection. In this case-control study, 65 Patients with COVID-19 were and 67 healthy controls were genotyped for their main functional polymorphisms namely, the 14-bp Ins/Del (rs371194629), +3003C/T (rs1707), +3010C/G (rs1710), +3027A/C (rs17179101), +3035C/T (rs17179108), +3142C/G (rs1063320), +3187A/G (rs9380142) and +3196C/G (rs1610696) in the exon 8 of the 3' untranslated regions (3' UTRs) using sanger sequencing method. Associations were assessed for five inheritance models (codominant, dominant, recessive, over-dominant and log-additive). Moreover, the levels of plasma soluble HLA-G (sHLA-G) were explored using ELISA method. Our results revealed that the 14-bp INS/DEL polymorphism was strongly associated with COVID-19 symptoms development for almost all tested inheritance models (p < 0.001). Inversely, the (+3196C/G) polymorphism exhibited a protective effect against COVID-19. In addition, three haplotypes; UTR-1, UTR-3, and UTR-5 were found associated with COVID-19 symptoms (p < 0.05), The level of HLA-G in the serum was significantly higher in COVID-19 individuals than in healthy individuals (p < 0.001).These findings suggest that HLA-G gene polymorphisms in the regulatory 3'UTR region of the HLA-G gene may influence the host immune response to SARS-CoV-2 infection. A deeper comprehension of the functional effect of these associated polymorphisms could be useful in identifying high-risk individuals and in developing adaptive treatments for patients.

Successful embryo implantation relies on a receptive endometrium and a maternofetal dialogue. Abnormal receptivity is a common cause of implantation failure in assisted reproductive techniques. This study aimed to develop a novel transcriptomic-based diagnostic assay, Adhesio, for assessing endometrial receptivity and guiding personalized embryo transfer. Adhesio was developed based on an initial dataset of 74 endometrial biopsies. Two types of biopsy samples were involved: 45 endometrial biopsies collected during the optimal theoretical window of implantation (WOI) and 29 endometrial biopsies which cells have been cultured with or without an autologous embryo. Microarray analysis was performed to identify differentially expressed genes associated with endometrial receptivity and selected candidate genes were assessed using quantitative real-time polymerase chain reaction (RT-qPCR) on biopsy samples. Statistical analyses were conducted to assess the performance and accuracy of Adhesio. The microarray analysis identified three distinct clusters of endometrial samples with differential gene expression patterns. Cluster 1 exhibited 1717 differentially expressed genes involved in biological processes associated with endometrial receptivity. A specific transcriptomic signature of 60 genes associated with endometrial co-culture was obtained using class prediction approach. Thereafter, an original panel of 10 genes was selected as potential biomarkers for endometrial receptivity based on their expression profiles in both endometrial biopsies and co-cultured cells. This article outlines the methodology employed to develop Adhesio, a test that assesses endometrial receptivity using an original panel of 10 genes. These genes are not only involved during the WOI but are also influenced by the maternal-fetal dialogue.

Shigellosis is a major cause of morbidity and mortality among children, especially in developing countries. The increased extended-spectrum beta-lactamase (ESBL) resistance in Shigella poses a challenge for effective treatment. To examine the antibiotic resistance and ESBL profile of Shigella isolates from children with acute diarrhea. Shigella was isolated from stool cultures from pediatric patients suffering from acute diarrhea. The isolates were identified by bacteriological tests, serotyping, and multiplex polymerase chain reaction (PCR). The antimicrobial resistance was examined by disc diffusion. Phenotypic tests and PCR examined the ESBLs and CTX-M, SHV, and TEM genes. A total of 100 Shigella (10% prevalence rate) were isolated. The S. sonnei and S. dysenteries were the most prevalent species (33% and 31%, respectively), followed by S. flexneri (27%), and only 9% were S. boydii. The isolates had complete resistance (100%) to ampicillin. There was lower resistance to ciprofloxacin (24%), and no resistance to imipenem. By phenotypic tests, 54% of isolates had ESBL. By PCR, bla-CTX-M gene was the most prevalent (50%), followed by bla-TEM (48.1%). Only one isolate (1.9%) had the bla-SHV gene. The alarmingly high rates of antibiotic resistance and ESBL resistance among Shigella spp highlight the urgent need to restrict the unguided use of these drugs. Continuous monitoring of local and global antibiotic resistance patterns is required to prevent the spread of resistance.

Repeated heating of edible oils at high temperatures and its use in cooking food generates polycyclic aromatic hydrocarbons (PAHs) that have carcinogenic potential. The use of repeatedly heated cooking oils (RHCO) is a common practice in India. The present investigation in Wistar rats was done to determine the genotoxic potential of consumption of food cooked in sunflower oil that has been repeatedly heated to boiling. The rats were fed a diet cooked-fried in such oil. The biomarkers of genotoxicity, comet assay, micronucleus test, and chromosomal aberrations in peripheral blood lymphocytes (PBL) of Wistar rats were used. Results of the present investigation reveal that rats fed on food cooked in oil that was 5 times repeatedly boiled induced significant Deoxy ribonucleic acid (DNA) damage in PBL and liver homogenate. Increased frequency of micronuclei and chromosomal aberrations in blood and bone marrow of rats were also observed. A similar observation was found in rats that were fed food cooked in oil that was boiled 3 times. However, the results of genotoxicity in rats that ate food cooked in oil heated only once were not statistically significant in comparison to the control rats that fed on food made in heated oil (not boiled). Intake of food cooked in repeatedly heated oil of different heating grades induced significant genotoxicity in rats evident by increased DNA damage and frequency of micronuclei and chromosomal aberrations. The presence of PAHs in heated oils triggers the generation of free radicals which could be the possible causative factor for the induced genetic damage. This study sheds light on the potential link between dietary habits involving the use of degraded oils and long-term health consequences.

The systematic phylogeny of Pleocyemata species, particularly within the family Nephropidae, remains incomplete. In order to enhance the taxonomy and systematics of Nephropidae within the evolutionary context of Pleocyemata, we embarked upon a comprehensive study aiming to elucidate the phylogenetic position of Nephropsis grandis. Consequently, we determined the complete mitochondrial DNA sequence for N. grandis. The circular genome spans a length of 15,344 bp and exhibits a gene composition analogous to that observed in other metazoans, encompassing a comprehensive set of 37 genes. Additionally, the genome features an AT-rich region. The rRNAs exhibited the highest AT content among the 37 genes (70.41%), followed by tRNAs (67.42%) and protein-coding genes (PCGs) (62.76%). The absence of a dihydrouracil arm in trnS1 prevented the formation of the canonical cloverleaf secondary structure. Selective pressure analysis indicated that the PCGs underwent purifying selection. The Ka/Ks ratios for cox1, cox2, cox3, and cob were considerably lower compared to other PCGs, implying strong purifying selection acting upon these particular genes. The mitochondrial gene order in N. grandis was consistent with the reported order in ancestral Pleocyemata. Phylogenetic revealed that N. grandis forms a cluster with the genus Metanephrops, and this cluster further groups with Homarus and the genus Nephrops within the Nephropidae family. These findings provide robust support for N. grandis as an ancestral member of the Nephropidae family. This study highlights the significance of employing complete mitochondrial genomes in phylogenetic analysis and deepens our understanding of the evolution of the Nephropidae family.

Asthma is a common chronic respiratory disease in children, the incidence rate of which has increased in recent years. Wilms tumour 1-associated protein (WTAP) is an N6-methyladenosine (m6A) methyltransferase. The purpose of this study was to explore the specific mechanism of WTAP in asthma progression, and clarify the intricate interplay between m6A modifications, WTAP, AXIN1, and their collective impact on airway smooth muscle cells (ASMCs) proliferation in asthma. Platelet-derived growth factor-BB (PDGF-BB)-treated ASMCs were used to establish an asthma model in vitro. The cell phenotype was tested using CCK-8, transwell, and wound healing assays. The expression of the Wnt signalling pathway was detected by western blotting. In addition, the relationship between WTAP/YTDHF2 and AXIN1 was assessed by a double luciferase reporter assay. Actinomycin D treatment and RT‒qPCR assays were performed to determine the mRNA stability of AXIN1. We found that WTAP was significantly increased in PDGF-BB-treated ASMCs. Knockdown of WTAP inhibited the excessive cell viability and migration of ASMCs induced by PDGF-BB. Furthermore, WTAP knockdown increased AXIN1 levels and inhibited the Wnt signalling pathway. Furthermore, WTAP knockdown decreased the m6A levels and enhanced the mRNA stability of AXIN1. WTAP overexpression showed the opposite effect. In addition, YTHDF2 was demonstrated to be the reader that recognizes the WTAP-mediated m6A modification of AXIN1. YTHDF2 knockdown enhanced the mRNA stability of AXIN1 and reversed the effect of WTAP overexpression on PDGF-BB-treated ASMCs. WTAP knockdown inhibited the excessive cell viability and migration of ASMCs by enhancing the m6A levels of AXIN1, which was further recognized by YTHDF2. The upregulation of AXIN1 mediated by the WTAP/YTHDF2 axis further inhibited the Wnt signalling pathway. Our study provides a new method for the treatment of asthma. This work not only deepens our understanding of the molecular underpinnings of asthma but also identifies potential therapeutic targets for the development of novel treatments aimed at inhibiting ASMC proliferation and alleviating asthma symptoms.

The parrot grunt fish, Pomadasys perotaei, has a limited distribution in the Eastern Atlantic Ocean and is an important species in marine capture fisheries across several West African countries. Despite its ecological and economic significance, the mitogenomic information for this species is lacking. This study utilized next-generation sequencing to generate the de novo mitogenome of P. perotaei from Eastern Atlantic. The resulting mitogenome is 16,691 base pairs and includes 13 protein-coding genes (PCGs), 22 transfer RNAs, two ribosomal RNAs, and an AT-rich control region (CR). Most of the PCGs exhibit nonsynonymous (Ka) and synonymous (Ks) substitution rates of less than '1', indicating strong negative selection across haemulid fishes. The control region of Pomadasys species contains four conserved domains, as seen in other teleost's, with polymorphic nucleotides that can be used to study population structures through the amplification of short mitochondrial gene fragments. Additionally, Bayesian phylogenetic analysis based on PCGs revealed a non-monophyletic clustering pattern of Pomadasys within the haemulid matrilineal tree. Overall, the structural characterization and phylogenetic analysis enhance our understanding of the genetic composition and evolutionary history of Pomadasys species from the Indo-West Pacific and Eastern Atlantic Oceans.

It was reported that serum apurinic/apyrimidinic endodeoxyribonuclease 1 (APEX1) level was higher in acute myocardial infarction (AMI) patients than in angina. This study aimed to investigate the role and mechanism of APEX1 in AMI progression. The mRNA and protein levels of APEX1 and zinc finger CCHC domain containing 9 (ZCCHC9) in blood specimens of AMI patients and normal controls were determined by RT-qPCR and Western blot assays, respectively. H9c2 cardiomyocytes were treated with angiotensin II (Ang II) to induce cardiomyocyte injury and then transfected with small interfering RNA against APEX1 (si-APEX1) or overexpression plasmids of ZCCHC9 (pcDNA-ZCCHC9). The cell viability, apoptosis, inflammatory cytokine levels, and fibrosis-associated protein expression in H9c2 cells were evaluated. ZCCHC9 promoter methylation were detected with methylation-specific PCR (MSP) assay. Then, rescue experiments were performed to explore whether APEX1 mediated cardiomyocyte functions by regulating ZCCHC9 expression. Furthermore, we explored whether the APEX1/ZCCHC9 axis regulated cardiomyocyte injury in AMI via the p38 MAPK signaling pathway. Additionally, an AMI rat model was established using the left anterior descending artery (LAD) ligation method and multipoint intramyocardial injection (5 points, 2 µL/point) of lentivirus (1 × 10⁹ TU/mL) carrying scramble or si-APEX1 was conducted before modeling. The rats were euthanized four weeks after AMI modeling, and blood samples and myocardial tissues were harvested. The infarct area, cell apoptosis, inflammation, and fibrosis in myocardial tissues were detected. APEX1 was upregulated and ZCCHC9 was downregulated in blood samples of AMI patients compared with normal controls. APEX1 knockdown or ZCCHC9 overexpression attenuated Ang II-induced viability reduction, apoptosis, inflammation, and fibrosis in cardiomyocytes. APEX1 inhibited ZCCHC9 expression by promoting DNA methyltransferase 1 (DNMT1)-mediated ZCCHC9 promoter methylation. ZCCHC9 knockdown abolished the protective effects of APEX1 knockdown on Ang II-induced cardiomyocyte injury. APEX1 knockdown inhibited the p38 MAPK signal signaling, and anisomycin reversed the effect of APEX1 knockdown on cardiomyocyte functions. Additionally, APEX1 knockdown alleviated apoptosis, inflammation, and fibrosis in myocardial tissues of AMI rats. APEX1 knockdown attenuated Ang II-induced apoptosis, inflammation, and fibrosis in cardiomyocytes although promoting ZCCHC9 expression and inhibiting the p38 MAPK signaling pathway, thus relieving myocardial infarction, inflammation, and fibrosis in AMI rats.

Maize is a major crop, feed, and industrial material. Caffeic acid-O-methyltransferase (COMT) is a methylase closely associated with lignin biosynthesis and plant growth and resistance. In this study, we identified the COMT gene (ZmCOMT) family in maize and further analyzed its phylogenetic evolution, subcellular localization, and its function in response to light. Thirty-one ZmCOMT genes were identified in the maize genome, which were distributed across eight chromosomes and mainly clustered on chromosome 4. Most ZmCOMT proteins were predicted to localize in the cytoplasm. Ten different conserved motifs were present in most ZmCOMT proteins, and motif1, motif6, and motif7 were highly conserved and present in all ZmCOMT proteins. The photoresponsivity elements were conserved among all members, and ZmCOMT22 and ZmCOMT10 genes responsive to light. This result suggests a potential function for these two genes in lignin biosynthesis which a previous study had linked to light regulation. Jasmonic acid responsive and abscisic acid cis-acting elements were present in the promoter regions of family members, thus the family may be regulated by hormone signaling pathways of maize. In summary, ZmCOMT genes are ancient, and the highly conserved motifs may be significant in survival and evolution of maize. Furthermore, light may influence lignin biosynthesis and photosynthesis through ZmCOMT genes. This research provided theoretical basis for lignin biosynthesis of maize and the potential value of ZmCOMT22 and ZmCOMT10 genes to enhance plant photosynthesis for facing global warming.