Journal of Applied Genetics最新文献

Lung cancer remains a leading cause of global cancer-related mortality, and the exploration of innovative therapeutic approaches, such as PD1/PDL1 immunotherapy, is critical. This study leverages comprehensive data from the Cancer Genome Atlas (TCGA) to investigate the differential expression of PD1/PDL1 in lung cancer patients and explores its implications. Clinical data, RNA expression, somatic mutations, and copy number variations of 1017 lung cancer patients were obtained from TCGA. Patients were categorized into high (HE) and low (LE) PD1/PDL1 expression groups based on mRNA levels. Analyses included differential gene expression, functional enrichment, protein-protein interaction networks, and mutational landscape exploration. The study identified 391 differentially expressed genes, with CD4 and PTPRC among the upregulated genes in the HE group. Although overall survival did not significantly differ between HE and LE groups, enrichment analysis revealed a strong association with immunoregulatory signaling pathways, emphasizing the relevance of PD1/PDL1 in immune response modulation. Notably, TP53 mutations were significantly correlated with high PD1/PDL1 expression. This study provides a comprehensive analysis of PD1/PDL1 expression in lung cancer, uncovering potential biomarkers and highlighting the intricate interplay between PD1/PDL1 and the immune response. The identified upregulated genes, including CD4 and PTPRC, warrant further investigation for their roles in the context of lung cancer and immunotherapy. The study underscores the importance of considering molecular heterogeneity in shaping personalized treatment strategies for lung cancer patients. Limitations, such as the retrospective nature of TCGA data, should be acknowledged.

In recent years, it has been generally accepted that metal-based nanoparticles (NPs) may induce stress in the endoplasmic reticulum (ER), a key organelle where protein folding occurs. We examined ER stress in immortalized human cerebral microvascular cells (hCMEC/D3) after exposure to silver-NPs (Ag-NPs)- and copper oxide-NPs (CuO-NPs) induced toxicity at < 10 nm and < 40 nm or < 50 nm diameters, respectively. In cytotoxicity assessments, cells were exposed to different CuO-NPs (5-400 µg/mL) or Ag-NPs (1-10 µg/mL) concentration ranges for 24 h and 72 h, and tetrazole salt reduction assays (EZ4U) were performed. Also, Ag-NP or CuO-NP effects on cell proliferation, apoptosis (caspase 3/7 assays), and ER stress and cell morphology were evaluated. In ER stress assessments, RNA-like endoplasmic reticulum kinase (PERK), activating transcription factor 6 (ATF6), inositol-requiring enzyme 1 (IRE1a), and others stress factor mRNA levels were determined after 24 h treatment using Real-Time PCR. Increased stress sensors (IRE1a, PERK, and ATF6) mRNA levels were observed after exposure to Ag-NPs (< 10 and < 40 nm) or CuO-NPs (< 50 nm). We investigated the expression of tight junction (TJ) proteins (barrier junctions) and showed that both types of NP reduced of OCLN gene expression. Morphological changes were observed after Ag-NP or CuO-NP exposure using holotomographic microscopy. Our data suggest that Ag- and CuO-NPs should undergo future in vitro and in vivo toxicology studies, especially for downstream biomedical application and occupational risk assessments.

Employing bioinformatics approaches, this investigation pinpointed pivotal differentially expressed genes (DEGs) across the spectrum of Alzheimer's disease (AD), from incipient to severe stages, using the GSE28146 dataset from the GEO repository. Analytical methods included DEG identification via the limma package in R, coupled with GO and KEGG pathway analyses through clusterProfiler, to discern biological processes and pathway involvements. Key findings spotlighted the roles of proteasome subunits PSMB4, PSMB8, PSMC4, and PSMD6 in the early stage, ribosomal proteins RPS3 and RPL11 during moderate AD, and mitochondrial components COX5B, COX6B2, and COX7A2 in severe AD, underscoring their importance in the disease's pathogenesis. Conclusively, these results not only delineate the dynamic genetic shifts accompanying AD progression but also propose critical biomarkers for potential therapeutic targeting, offering a consolidated basis for future AD research and treatment development. This offered a novel idea for analyzing the pathogenesis and development of AD and investigation of targeted drugs.

Genotype-limited plant regeneration is one of the main obstacles to the broader use of genetic transformation in barley breeding. Thus, developing new approaches that might improve responses of in vitro recalcitrant genotypes remains at the center of barley biotechnology. Here, we analyzed different barley genotypes, including "Golden Promise," a genotype commonly used in the genetic transformation, and four malting barley cultivars of poor regenerative potential. The expression of hormone-related transcription factor (TF) genes with documented roles in plant regeneration was analyzed in genotypes with various plant-regenerating capacities. The results indicated differential expression of auxin-related TF genes between the barley genotypes in both the explants and the derived cultures. In support of the role of auxin in barley regeneration, distinct differences in the accumulation of free and oxidized auxin were observed in explants and explant-derived callus cultures of barley genotypes. Following the assumption that modifying gene expression might improve plant regeneration in barley, we treated the barley explants with trichostatin A (TSA), which affects histone acetylation. The effects of TSA were genotype-dependent as TSA treatment improved plant regeneration in two barley cultivars. TSA-induced changes in plant regeneration were associated with the increased expression of auxin biosynthesis-involved TFs. The study demonstrated that explant treatment with chromatin modifiers such as TSA might provide a new and effective epigenetic approach to improving plant regeneration in recalcitrant barley genotypes.

Apart from apomictic types, the Polygonum-type eight-nuclear embryo sac is considered to be dominant in grasses. A triploid endosperm is formed as a result of double fertilisation. This study showed, for the first time, the dominance of diploid nuclei in the syncytial stage of the central cell of embryo sac in oat species and amphiploids. The dominance of diploid nuclei, which were the basis for the formation of polyploid nuclei, was weaker in amphiploids due to aneuploid events. The genomic in situ hybridisation method applied in the study did not distinguish the maternal and paternal haploid nuclei of embryo sac. However, this method demonstrated the lack of a set of genomes of one haploid nucleus. Embryological analyses of the initial stages of oat endosperm development revealed a fertilised egg cell, and two polar nuclei differing in size. It can be assumed that the formation of diploid oat endosperm occurred after the fusion of one polar nucleus and the nucleus of a male gamete, while the second polar nucleus gave rise to 1n nuclei. The levels of ploidy of syncytial nuclei were not influenced by both aneuploid events and correlated with pollen developmental anomalies. The differences in the analysed cytogenetic events distinguished amphiploids and their parental species in the ordination space.

Mammary gland tumours (MGTs) are commonly occurring neoplasms in female dogs. However, rare cases of MGTs in male dogs have been reported for years. Due to the low incidence of MGTs in male dogs in comparison to female dogs, veterinary oncology is mainly focused on mammary neoplasms diagnosed in female dogs and extensive research is conducted in this scientific area. Therefore, there are no sufficient epidemiological data on male dogs and the aetiology of their tumour development is still poorly understood.The aim of this literature review was to present cases of MGTs in male dogs for better understanding the scale of the problem over the years. The analyses of 74 affected male dogs with 92 tumours showed that the majority of MGTs in male dogs were benign tumours (54.3%), especially in form of adenomas, often developed in posterior canine mammary glands (58.1%).The increased number of canine MGTs in male dogs aged 7 -13 years with an age peak at 11 years was noted. The age of affected animals was not related to breed. Mammary gland neoplasms were diagnosed predominately in Crossbreeds (20.2%) followed by Cocker Spaniels (18.9%) and German Shepherds (10.8%).The association between MGT development in male dogs and co-occurrence of testicular tumours (TTs) has been discussed for years. Thus, cases of development of both tumours were included in this study. As a result, only in 12.7% cases of MGTs also history of TTs was described. Therefore, no general association between these tumours should be assumed.

Lambdoid bacteriophages are excellent models in studies on molecular aspects of virus-host interactions. However, some of them carry genes encoding toxins which are responsible for virulence of pathogenic strains of bacteria. Shiga toxin-converting bacteriophages (Stx phages) encode Shiga toxins that cause virulence of enterohemorrhagic Escherichia coli (EHEC), and their effective production depends on Stx prophage induction. The exo-xis region of the lambdoid phage genome consists of genes which are dispensable for the phage multiplication under laboratory conditions; however, they might modulate the virus development. Nevertheless, their exact effects on the phage and host physiology remained unclear. Here, we present results of complex studies on the role of the exo-xis region of bacteriophage Φ24_B, one of Stx2b phages. Transcriptomic analyses, together with proteomic and metabolomic studies, provided the basis for understanding the functions of the exo-xis region. Genes from this region promoted lytic development of the phage over lysogenization. Moreover, expression of the host genes coding for DnaK, DnaJ, GrpE, and GroELS chaperones was impaired in the cells infected with the Δexo-xis phage mutant, relative to the wild-type virus, corroborating the conclusion about lytic development promotion by the exo-xis region. Proteomic and metabolomic analyses indicated also modulation of gad and nrf operons, and levels of amino acids and acylcarnitines, respectively. In conclusion, the exo-xis region controls phage propagation and host metabolism by influencing expression of different phage and bacterial genes, directing the virus to the lytic rather than lysogenic developmental mode.

Burkitt lymphoma (BL) is a highly aggressive lymphoma that mainly affects children and young adults. Chemotherapy is effective in young BL patients but the outcome in adults is less satisfactory. Therefore, there is a need to enhance the cytotoxic effect of drugs used in BL treatment. Glutathione (GSH) is an important antioxidant involved in processes such as regulation of oxidative stress and drug detoxification. Elevated GSH levels have been observed in many cancers and were associated with chemoresistance. We previously identified GCLC, encoding an enzyme involved in GSH biosynthesis, as an essential gene in BL. We now confirm that knockout of GCLC decreases viability of BL cells and that the GCLC protein is overexpressed in BL tissues. Moreover, we demonstrate that buthionine sulfoximine (BSO), a known inhibitor of GCLC, decreases growth of BL cells but does not affect control B cells. Furthermore, we show for the first time that BSO enhances the cytotoxicity of compounds commonly used in BL treatment, doxorubicin, and cyclophosphamide. Given the fact that BSO itself was not toxic to control cells and well-tolerated in clinical trials, combination of chemotherapy with BSO may allow reduction of the doses of cytotoxic drugs required to obtain effective responses in BL patients.

Due to high antimicrobial resistance and biofilm-forming ability, Pseudomonas aeruginosa is one of the seriously life-threatening agents causing chronic and nosocomial infections. This study was performed to determine the antibiotic resistance pattern, biofilm formation, and frequency of biofilm-related genes in P. aeruginosa strains. In total, 123 P. aeruginosa isolates were collected from different clinical sources. Antimicrobial susceptibility testing (AST) was performed to detect multidrug-resistant P. aeruginosa (MDRPA) isolates. To evaluate the biofilm-forming isolates, the microtiter plate (MTP) method was carried out. Also, the prevalence of biofilm genotype patterns, including pslA, pslD, pelA, pelF, and algD genes, was detected by polymerases chain reaction (PCR). According to our findings, the highest resistance and susceptibility rates were found in ceftazidime with 74.7% (n = 92) and ciprofloxacin with 42.2% (n = 52), respectively. In our study, the highest level of antibiotic resistance belonged to wound isolates which meropenem had the most antibacterial activity against them. In total, 86.1% (n = 106) P. aeruginosa isolates were determined as MDRPA, of which 61.3% (n = 65) were able to form strong biofilm. The highest and lowest frequency of biofilm-related genes among biofilm producer isolates belonged to pelF with 82.1% (n = 101) and algD with 55.2% (n = 68), respectively. The findings of the conducted study indicate a significant relationship between MDRPA and biofilm genotypic/phenotypic patterns, suggesting the necessity of a careful surveillance program in hospital settings.

Diffuse large B-cell lymphoma (DLBCL) stands as a formidable challenge in the landscape of non-Hodgkin's lymphomas. This review illuminates the remarkable strides made in comprehending DLBCL's molecular intricacies and devising targeted treatments. DLBCL, the most prevalent non-Hodgkin's lymphoma, has seen transformative progress in its characterization. Genetic investigations, led by high-throughput sequencing, have unveiled recurrent mutations in genes such as MYC, BCL2, and BCL6, casting light on the underlying genetic chaos propelling DLBCL's aggressiveness. A pivotal facet of this understanding centers on cell signaling pathways. Dysregulation of B-cell receptor (BCR) signaling, NF-κB, PI3K/Akt/mTOR, JAK/STAT, Wnt/β-Catenin, and Toll-like receptor pathways plays a critical role in DLBCL pathogenesis, offering potential therapeutic targets. DLBCL's complex tumor microenvironment (TME) cannot be overlooked. The dynamic interplay among tumor cells, immune cells, stromal components, and the extracellular matrix profoundly influences DLBCL's course and response to therapies. Epigenetic modifications, including DNA methylation and histone changes, add another layer of intricacy. Aberrant epigenetic regulation plays a significant role in lymphomagenesis, offering prospects for epigenetic-based therapies. Promisingly, these molecular insights have spurred the development of personalized treatments. Targeted therapies and immunotherapies, guided by genomic profiling and molecular classification, are emerging as game-changers in DLBCL management. In conclusion, this review underscores the remarkable strides in understanding DLBCL's molecular underpinnings, spanning genetics, cell signaling, the tumor microenvironment, and epigenetics. These advances pave the way for more effective, personalized treatments, renewing hope for DLBCL patients.