Expression Profiles Research Articles

Immune Regulatory Circular RNAs, circRasGEF1B and circHIPK3, are Upregulated in Peripheral Blood Mononuclear Cells of COVID-19 Patients.

Background: COVID-19 is one of the worst pandemics worldwide, and its diagnosis and treatment are of great importance. Recent evidence has shown that circular RNA (circRNA deregulation is involved in different infectious diseases. In the present study, we tried to investigate the expression of cirRNAs RasGEF1B (hsa_circ_0127052), HIPK3 (hsa_circ_100783), and GATAD2A (hsa_circ_0050236) in COVID-19 patients. Methods: Using quantitative real-time polymerase chain reaction, the expression profiles of candidate circRNAs were detected in 57 COVID-19 patients and 51 healthy controls. As part of the process of identifying a candidate circRNA that is sensitive and specific, receiver operating characteristic (ROC) curves were also utilized. Results: Our results showed higher expression levels of circRasGEF1B and circHIPK3 in COVID-19 patients, however, circGATAD2A showed no statistical difference between patients and controls. ROC curves showed that circRasGEF1B (hsa_circ_0127052), and HIPK3 (hsa_circ_100783) had favorable specificity and sensitivity, whereas GATAD2A (hsa_circ_0050236) did not. Conclusion: In summary, our study highlights the potential of CircRasGEF1B (hsa_circ_0127052) and HIPK3 (hsa_circ_100783) as biomarkers for COVID-19 diagnosis due to their high expression levels and demonstrated diagnostic accuracy. These findings suggest that circRNAs could play a crucial role in the development of diagnostic tools for COVID-19, providing a new avenue for early detection and management of the disease.

Comprehensive mapping of somatotroph pituitary neuroendocrine tumour heterogeneity using spatial and single-cell transcriptomics.

Pituitary neuroendocrine tumours (PitNETs) are common intracranial tumours that are highly heterogeneous with unpredictable growth patterns. The driver genes and mechanisms that are crucial for tumour progression in somatotroph PitNETs are poorly understood. In this study, we performed integrative spatial transcriptomics (ST) and single-cell RNA sequencing (scRNA-seq) analysis on somatotroph tumours and normal pituitary samples to comprehensively characterize the differences in cellular characteristics. By analyzing combined copy number variations (CNVs), tumour tissues were divided into two regions, which included the CNVhigh and CNVlow areas. The protumour genes DLK1 and RCN1 were highly expressed in the CNVhigh area, which might be related to tumour progression and could be targeted for precision therapy. We also found that the transforming growth factor beta signalling pathway participated in tumour progression and identified heterogeneity in the expression profiles of key genes. We assessed the intertumoral and intratumoral heterogeneity in somatotroph PitNETs and emphasized the importance of individualized treatment. In summary, we visualized the cellular distribution and transcriptional differences in normal pituitary and somatotroph PitNETs by ST and scRNA-seq for the first time. This study provides a strong theoretical foundation to comprehensively understand the crucial mechanisms involved in tumour progression and develop new strategies to treat somatotroph PitNETs. The first-ever visualization of cellular distributions in normal and tumor pituitary tissues. The inter- and intra-tumoral transcriptomic heterogeneity of somatotroph PitNETs was comprehensively revealed. Identification of potential protumor factors and critical signaling pathways, opening new avenues for therapeutic intervention.

Neuroplasticity and neuroimmune interactions in fatal asthma.

Alteration of airway neuronal function and density and bidirectional interaction between immune cells and sensory peripheral nerves have been proposed to trigger and perpetuate inflammation that contribute to asthma severity. To date, few studies analysed neuroplasticity and neuroinflammation in tissue of asthmatic individuals. We hypothesized that the presence of these phenomena would be a pathological feature in fatal asthma. We have quantified the expression of the pan-neuronal marker PGP9.5 and the neuronal sensory-derived neuropeptide calcitonin gene-related peptide (CGRP) in the large airways of 12 individuals deceased due to an asthma attack and compared to 10 control lung samples. The proximity between nerve bundles to eosinophils, mast cells and CADM1+ cells was also quantified. We have additionally developed a hPSC-derived sensory neuron/mast cell co-culture model, from where mast cells were purified and differences in gene expression profile assessed. Fatal asthma patients presented a higher PGP9.5 and CGRP positive area in the airways, indicating sensory neuroplasticity. Eosinophils, mast cells and CADM1+ cells were observed in close contact or touching the airway nerve bundles, and this was found to be statistically higher in fatal asthma samples. Invitro co-culture model showed that human mast cells adhere to sensory neurons and develop a distinct gene expression profile characterized by upregulated expression of genes related to heterophilic adhesion, activation and differentiation markers, such as CADM4, PTGS2, C-KIT, GATA2, HDC, CPA3, ATXN1 and VCAM1. Our results support a significant role for neuroplasticity and neuroimmune interactions in fatal asthma, that could be implicated in the severity of the fatal attack. Accordingly, the presence of physical neuron and mast cell interaction leads to differential gene expression profile in the later cell type.

Elucidation of the role of XBP1 in the progression of complete hydatidiform mole to invasive mole through RNA-seq

ObjectiveA complete hydatidiform mole (CHM) is a common disease and is known to develop post-molar gestational trophoblast neoplasia (GTN). However, the molecular mechanisms underlying the progression of CHM to post-molar GTN remain largely unknown. In this study, we investigated the molecular factors associated with the progression using RNA-seq. MethodsWe included 13 patients with CHM and performed RNA-seq using freshly frozen samples. We identified differentially expressed genes between patients who developed GTN (GTN group) and those who achieved spontaneous remission after uterine evacuation (SR group), and performed pathway analysis. Then, functional analyses were performed on choriocarcinoma (JAR and JEG-3) and CHM (Hmol1-3B and Hmol1-2C) cells. Moreover, we evaluated the in vivo tumorigenicity of XBP1-overexpressed Hmol1-3B cells. ResultsThe gene expression profiles were separated into two groups, and an upstream regulator analysis was performed using 281 differentially expressed genes. We focused on transcription factors and identified that 33 transcription factors were activated in the GTN group. Then, excluding those with low expression levels in clinical samples and cell lines, XBP1 was selected for further analysis. Additionally, XBP1 downregulation significantly decreased the migration and invasive abilities of choriocarcinoma cells, whereas XBP1 overexpression significantly increased the migration and invasive abilities of CHM cells. Furthermore, animal experiments showed that tumor weight and blood human chorionic gonadotropin (hCG) levels were significantly higher in the XBP1-overexpressing Hmol1-3B-bearing mice than those in the control mice. ConclusionRNA-seq identified XBP1 as a key factor in post-molar GTN, suggesting it contributes to the development of post-molar GTN.

Identifying the ceRNA Regulatory Network in Early-Stage Acute Pancreatitis and Investigating the Therapeutic Potential of NEAT1 in Mouse Models.

Acute pancreatitis (AP) is a common digestive disorder characterized by high morbidity and mortality. This study aims to uncover differentially expressed long noncoding RNAs (lncRNAs) and mRNAs, as well as related pathways, in the early stage of acute pancreatitis (AP), with a focus on the role of Neat1 in AP and severe acute pancreatitis (SAP). In this study, we performed high-throughput RNA sequencing on pancreatic tissue samples from three normal mice and three mice with cerulein-induced AP to describe and analyze the expression profiles of long non-coding RNAs (lncRNAs) and mRNAs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were conducted on the differentially expressed mRNAs to identify enriched pathways and biological processes. An lncRNA-miRNA-mRNA interaction network was constructed to elucidate potential regulatory mechanisms. Furthermore, we utilized Neat1 knockout mice to investigate the role of Neat1 in the pathogenesis of cerulein-AP and L-arginine-severe acute pancreatitis (SAP). Our results revealed that 261 lncRNAs and 1522 mRNAs were differentially expressed in the cerulein-AP group compared to the control group. GO and KEGG analyses of the differentially expressed mRNAs indicated that the functions of the corresponding genes are enriched in cellular metabolism, intercellular structure, and positive regulation of inflammation, which are closely related to the central events in the pathogenesis of AP. A ceRNA network involving 5 lncRNAs, 226 mRNAs, and 61 miRNAs were constructed. Neat1 was identified to have the potential therapeutic effects in AP. Neat1 knockout in mice inhibited pyroptosis in both the AP/SAP mouse models. We found that lncRNAs, particularly Neat1, play a significant role in the pathogenesis of AP. This finding may provide new insights into further exploring the pathogenesis of SAP and could lead to the identification of new targets for the treatment of AP and SAP.

Single cell atlas reveals multilayered metabolic heterogeneity across tumour types

Metabolic reprogramming plays a pivotal role in cancer progression, contributing to substantial intratumour heterogeneity and influencing tumour behaviour. However, a systematic characterization of metabolic heterogeneity across multiple cancer types at the single-cell level remains limited. We integrated 296 tumour and normal samples spanning six common cancer types to construct a single-cell compendium of metabolic gene expression profiles and identify cell type-specific metabolic properties and reprogramming patterns. A computational approach based on non-negative matrix factorization (NMF) was utilised to identify metabolic meta-programs (MMPs) showing intratumour heterogeneity. In-vitro cell experiments were conducted to confirm the associations between MMPs and chemotherapy resistance, as well as the function of key metabolic regulators. Survival analyses were performed to assess clinical relevance of cellular metabolic properties. Our analysis revealed shared glycolysis upregulation and divergent regulation of citric acid cycle across different cell types. In malignant cells, we identified a colorectal cancer-specific MMP associated with resistance to the cuproptosis inducer elesclomol, validated through in-vitro cell experiments. Furthermore, our findings enabled the stratification of patients into distinct prognostic subtypes based on metabolic properties of specific cell types, such as myeloid cells. This study presents a nuanced understanding of multilayered metabolic heterogeneity, offering valuable insights into potential personalized therapies targeting tumour metabolism. National Key Research and Development Program of China (2021YFA1300601). National Natural Science Foundation of China (key grants 82030081 and 81874235). The Shenzhen High-level Hospital Construction Fund and Shenzhen Basic Research Key Project (JCYJ20220818102811024). The Lam Chung Nin Foundation for Systems Biomedicine.

CD47 and Calreticulin Expression in Breast Cancer Subtypes and Anti-CD47 Inhibitory Effects in Macrophage-mediated Phagocytosis.

Macrophage-mediated cancer immune evasion is modulated by the balance between "the cluster of differentiation 47 (CD47), an anti-phagocytic signal" and "calreticulin (CALR), a pro-phagocytic signal". CD47 is highly expressed in various types of cancer. However, the expression profiles of CD47 and CALR in breast cancer, especially in different hormone receptor subtypes, and the effects of CD47 blockade in macrophage-mediated therapy are not well understood. The expression levels of CD47 and CALR were investigated in breast cancer and adjacent normal tissues using immunohistochemistry. To study the effects of CD47 blockade therapy, CD47 and CALR expression in breast cancer cell lines were determined. In vitro macrophage-mediated phagocytosis of breast cancer upon treatment with a monoclonal CD47 antibody (B6H12) were performed. CD47 and CALR were overexpressed in breast cancer tissues and their up-regulation was associated with hormone receptor subtypes. Patients with Luminal A breast cancer had higher levels of CD47, while patients with triple-negative breast cancer (TNBC) had higher levels of CALR. The levels of CD47 and CALR were also elevated in breast cancer cell lines of Luminal A (MCF-7) and TNBC (MDA-MB-231) subtypes. Interestingly, the expression ratio of surface CD47/CALR was significantly higher in MCF-7. Moreover, in vitro phagocytosis assays revealed that blockage of CD47 enhanced macrophage-mediated activity in both cancer cells with dramatically higher degrees of phagocytosis in MCF-7. The expression profiles of CD47 and CALR in breast cancer subtypes and the benefit of CD47 blocking-based immunotherapy are herein provided.

Unravelling the genetic basis of Azoospermia: RNA-Sequence and transcriptome profiling analyses in a Greek Population.

ObjectiveTo investigate whether idiopathic non-obstructive azoospermia (iNOA) has its own transcriptomic signature. DesignTesticular tissue biopsies, were retrieved, processed and prepared for RNA extraction from 26 consented patients diagnosed with iNOA. Samples were grouped into four pools based on the presence of testicular spermatozoa: two replicate pools for “No presence” (Null-spz-1 & Null-spz-2 pools), one for “High presence” (High-spz pool) and one for “Rare presence” (Rare-spz pool). A second set of replicate pools (CF-1 & CF-2) was used from patients with obstructive azoospermia (OA), served as controls. RNA sequencing (RNA-seq) and comparative Transcriptomics Analysis (CTA) were performed, followed by differential gene expression analysis (DGE) focused on protein-coding genes only. Differentially expressed genes (DEGs) exclusively upregulated or downregulated were further analyzed using the Gene Ontology (GO), STRING, and Kyoto Encyclopedia of Genes and Genome (KEGG) bioinformatic platforms. SubjectsMales diagnosed with iNOA. ExposureTesticular biopsies from men diagnosed with iNOA. Main Outcome MeasuresProtein-coding differentially expressed genes (DEGs). ResultsA significantly altered transcriptomic profile of protein-coding genes was identified in the testicular tissues from men with iNOA. A total of 3858 genes, exhibited dysregulated expression, with 1994 genes being exclusively downregulated and 1734 upregulated. Biological processes (BPs) such as, male gamete generation (GO:0048232) and meiotic cycle (GO:0051321) were significantly enriched by the downregulated DEGs while the upregulated DEGs enriched BPs such as, regulation of cell death (GO:0010941), regulation of cell adhesion (GO:0030155) and defense response (GO:0006952). Interactome analysis identified hub genes among the downregulated DEGs, including PCNA, PLK1, MCM4, CDK1, CCNB1, AURKA, CCNA2, and CDC6 and among the upregulated DEGs, including EGFR, RELA, CTNNB1, MYC, JUN, SMAD3, STAT3 NFKB1, TGFB1 and ACTB. Additionally, KEGG analysis demonstrated that pathways such as cell cycle (hsa04110) and Oocyte meiosis (hsa04114) are the primarily affected by the downregulated genes, while the upregulated genes mainly affected pathways such as, the Focal adhesion (hsa04510) and the PI3-Akt signaling pathway (hsa04151). ConclusionA distinct mRNA expression profile and altered transcriptomic activity were identified in the testicular tissues of men with iNOA.

Effects of Chlorella sp. and Schizochytrium sp. extracts on growth indices, body composition, and gene expression profiles in rainbow trout (Oncorhynchus mykiss)

Effects of Chlorella sp. and Schizochytrium sp. extracts on growth indices, body composition, and gene expression profiles in rainbow trout (Oncorhynchus mykiss)

Identification, functional analysis of chitin-binding proteins and the association of its single nucleotide polymorphisms with Vibrio parahaemolyticus resistance in Penaeus vannamei

Chitin-binding proteins (CBPs) play pivotal roles in numerous biological processes in arthropods, including growth, molting, reproduction, and immune defense. However, their function in the antibacterial immune defense of crustaceans remains relatively underexplored. In this study, twenty CBPs were identified and characterized in Penaeus vannamei. Expression profiling highlighted that the majority of CBPs were highly expressed in the intestine and hepatopancreas and responded to challenge by Vibrio parahaemolyticus. To explore the role of these CBPs in innate immunity, six CBPs (PvPrg4, PvKrtap16, PvPT-1a, PvPT-1b, PvExtensin and PvCP-AM1159) were selected for RNAi experiments. Silencing of only PvPrg4 and PvKrtap16 significantly decreased the cumulative mortality of V. parahaemolyticus-infected shrimp. Further studies demonstrated that inhibition of PvPrg4 and PvKrtap16 resulted in a marked upregulation of genes associated with the NF-κB and JAK-STAT signaling pathways, as well as antimicrobial peptides (AMPs), in both the intestine and hepatopancreas. These results collectively suggested that PvPrg4 and PvKrtap16 potentially promote V. parahaemolyticus invasion by negatively regulating the JAK-STAT and NF-κB pathways, thereby inhibiting the expression of AMPs. In addition, SNP analysis identified three SNPs in the exons of PvPrg4 that were significantly associated with tolerance to V. parahaemolyticus. Taken together, these findings are expected to assist in the molecular marker-assisted breeding of P. vannamei associated with anti-V. parahaemolyticus traits, as well as expand our understanding of CBP functions within the immune regulatory system of crustaceans.

The Arabidopsis splicing factor PORCUPINE/SmE1 orchestrates temperature-dependent root development via auxin homeostasis maintenance.

Appropriate abiotic stress response is pivotal for plant survival and makes use of multiple signaling molecules and phytohormones to achieve specific and fast molecular adjustments. A multitude of studies has highlighted the role of alternative splicing in response to abiotic stress, including temperature, emphasizing the role of transcriptional regulation for stress response. Here we investigated the role of the core-splicing factor PORCUPINE (PCP) on temperature-dependent root development. We used marker lines and transcriptomic analyses to study the expression profiles of meristematic regulators and mitotic markers, and chemical treatments, as well as root hormone profiling to assess the effect of auxin signaling. The loss of PCP significantly alters RAM architecture in a temperature-dependent manner. Our results indicate that PCP modulates the expression of central meristematic regulators and is required to maintain appropriate levels of auxin in the RAM. We conclude that alternative pre-mRNA splicing is sensitive to moderate temperature fluctuations and contributes to root meristem maintenance, possibly through the regulation of phytohormone homeostasis and meristematic activity.

Interferon Regulatory Factors (IRF1, IRF4, IRF5, IRF7 and IRF9) in Sichuan taimen (Hucho bleekeri): Identification and Functional Characterization

Background/Objectives: Interferon regulatory factors (IRFs) are multifunctional transcription factors that play important roles in the transcriptional regulation of interferons and in the immune response to pathogens. Therefore, studying the interferon system in fish is highly relevant in the prevention and treatment of viral diseases. Methods: In this study, five IRF genes (IRF1, IRF4, IRF5, IRF7 and IRF9) were identified and characterized in Hucho bleekeri, and their expression profiles were determined after LPS and Poly(I:C) treatment. Results: These IRFs have typical DNA-binding domains and IRF-association domains. Amino acid sequence comparison revealed high homology between these IRFs and those of other vertebrates, with the highest homology being with other salmonid fish. Phylogenetic analysis revealed that these IRFs are divided into four subfamilies (IRF1, IRF3, IRF4 and IRF5), with both IRF4 and IRF9 belonging to the IRF4 subfamily. IRF genes were widely expressed in all of the tested tissues, with IRF1, IRF4 and IRF9 being highly expressed in the spleen and kidney and IRF5 and IRF7 highly expressed in the gonads. IRF1, IRF4 and IRF5 expression was induced at different time points post-LPS challenge. IRF7 and IRF9 expression in the spleen and head kidney was not significantly altered by LPS induction. Poly(I:C) treatment altered IRF expression more significantly than LPS treatment. Poly(I:C) significantly altered the spleen and head kidney expression of all five IRFs. Conclusions: These findings reveal the potential role of IRFs in the antiviral response of H. bleekeri and provide a reference for examining signal transduction pathways in the interferon system in fish.

Correlating the genetic alterations and expression profile of the TRA2B gene in HNSCC and LUSC.

Transformer (TRA2B) is a serine/arginine-rich (SR)-like protein family that regulates the alternative splicing of several genes in a concentration-dependent manner. Amplification of the TRA2B gene, which codes for TRA2B, occurs in several malignancies, including those of the lung, cervix, head and neck, ovary, stomach, and uterine.

Changes in Gene Expression Profile with Age in SAMP8: Identifying Transcripts Involved in Cognitive Decline and Sporadic Alzheimer’s Disease

Background: The senescence-accelerated mouse 8 (SAMP8) represents a model for Alzheimer’s disease (AD) research because it exhibits age-related learning and memory impairments consistent with early onset and rapid progression of senescence. To identify transcriptional changes during AD progression, in this study, we analyzed and compared the gene expression profiles involved in molecular pathways of neurodegeneration and cognitive impairment in senescence-accelerated resistant 1 (SAMR1) and SAMP8 mice. Methods: In total, 48 female SAMR1 and SAMP8 mice were randomly divided into six groups (SAMR1 and SAMP8 at 3, 7, and 9 months of age). Microarray analysis of 22,000 genes was performed, followed by functional analysis using Gene Ontology (NCBI) and examination of altered molecular pathways using the KEGG (Kyoto Encyclopedia of Genes and Genomes). Results: SAMP8 mice had 2516 dysregulated transcripts at 3 months, 2549 transcripts at 7 months, and 2453 genes at 9 months compared to SAMR1 mice of the same age. These accounted for 11.3% of the total number. This showed that with age, the gene expression of downregulated transcripts increases, and that of over-expressed transcripts decreases. Most of these genes were involved in neurodegenerative metabolic pathways associated with Alzheimer’s disease: apoptosis, inflammatory response, oxidative stress, and mitochondria. The qPCR results indicated that Ndufs4, TST/Rhodanese, Wnt3, and Sema6a expression was differentially expressed during aging. Conclusions: These results further revealed significant differences in gene expression profiles at different ages between SAMR1 and SAMP8 and showed alteration in genes involved in age-related cognitive decline and mitochondrial processes, demonstrating the relevance of the SAMP8 model as a model for sporadic AD.

Expression Profiling Identified TRPM7 and HER2 as Potential Targets for the Combined Treatment of Cancer Cells.

TRPM7 is a divalent cation-permeable channel that is highly active in cancer cells. The pharmacological inhibitors of TRPM7 have been shown to suppress the proliferation of tumor cells, highlighting TRPM7 as a new anticancer drug target. However, the potential benefit of combining TRPM7 inhibitors with conventional anticancer therapies remains unexplored. Here, we used genome-wide transcriptome profiling of human leukemia HAP1 cells to examine cellular responses caused by the application of NS8593, the potent inhibitor of the TRPM7 channel, in comparison with two independent knockout mutations in the TRPM7 gene introduced by the CRISPR/Cas9 approach. This analysis revealed that TRPM7 regulates the expression levels of several transcripts, including HER2 (ERBB2). Consequently, we examined the TRPM7/HER2 axis in several non-hematopoietic cells to show that TRPM7 affects the expression of HER2 protein in a Zn2+-dependent fashion. Moreover, we found that co-administration of pharmacological inhibitors of HER2 and TRPM7 elicited a synergistic antiproliferative effect on HER2-overexpressing SKBR3 cells but not on HER2-deficient MDA-MB-231 breast cancer cells. Hence, our study proposes a new combinatorial strategy for treating HER2-positive breast cancer cells.

Nosocomial Transmission of Necrotizing Fasciitis: A Molecular Characterization of Group A Streptococcal DNases in Clinical Virulence

Streptococcus pyogenes, or Group A Streptococcus (GAS), is responsible for over 500,000 deaths per year. Approximately 15% of these deaths are caused by necrotizing soft-tissue infections. In 2008, we isolated an M5 GAS, named the LO1 strain, responsible for the nosocomial transmission of necrotizing fasciitis between a baby and a nurse in Belgium. To understand this unusual transmission route, the LO1 strain was sequenced. A comparison of the LO1 genome and transcriptome with the reference M5 Manfredo strain was conducted. We found that the major differences were the presence of an additional DNase and a Tn916-like transposon in the LO1 and other invasive M5 genomes. RNA-seq analysis showed that genes present on the transposon were barely expressed. In contrast, the DNases presented different expression profiles depending on the tested conditions. We generated knock-out mutants in the LO1 background and characterized their virulence phenotype. We also determined their nuclease activity on different substrates. We found that DNases are dispensable for biofilm formation and adhesion to both keratinocytes and pharyngeal cells. Three of these were found to be essential for blood survival; Spd4 and Sdn are implicated in phagocytosis resistance, and Spd1 is responsible for neutrophil extracellular trap (NET) degradation.

LncRNA HAGLROS: A Vital Oncogenic Propellant in Various Human Cancers.

HAGLR Opposite Strand lncRNA (HAGLROS) is a long non-coding RNA (lncRNA) located on the long arm of human chromosome 2 at locus 2q31.1. Emerging evidence highlights HAGLROS as a pivotal player in human cancers, characterized by its significant upregulation across multiple malignancies where it functions as an oncogenic driver. Its aberrant expression is closely linked to the initiation and progression of 13 distinct cancer types, notably correlating with adverse clinical outcomes and reduced overall survival rates in 9 of these cancer types. Mechanistically, HAGLROS is under the regulatory influence of the transcription factor STAT3, exerts competitive binding to 9 miRNAs, activates 5 signaling pathways pivotal for cancer cell proliferation and metastasis, as well as intricately modulates gene expression profiles. Given its multifaceted roles, HAGLROS emerges as a promising candidate for cancer diagnostics and prognostics. Moreover, its potential as a therapeutic target holds considerable promise for novel treatment strategies in oncology. This review synthesizes current research on HAGLROS, covering its expression patterns, biological roles, and clinical significance in cancer. By shedding light on these aspects, this review aims to contribute new perspectives that advance our understanding of cancer biology, enhance diagnostic accuracy, refine prognostic assessments, and pave the way for targeted therapeutic interventions.

The Effect of Long-Term Physical Disability and Aging on Extracellular Matrix Biogenesis in Human Skeletal Muscle

Physical inactivity and aging cause significant impairments in the functionality and mechanical properties of skeletal muscles, as well as remodeling of the extracellular matrix (ECM). We aimed to study the effect of long-term inactivity and age on the biogenesis of ECM in skeletal muscle. For quantitative mass spectrometry-based proteomic analysis and RNA sequencing, biopsy samples were taken from m. vastus lateralis in 15 young healthy volunteers, 8 young and 37 elderly patients with long-term primary osteoarthritis of the knee/hip joint – which is a model for studying the effects of inactivity on muscles. We detected 1022 mRNAs and 101 ECM and associated proteins (matrisome). An increase in the expression of two dozen highly abundant matrisome proteins, specific to elderly and young patients (in relation to young healthy people), was detected; however, changes in the expression of mRNA encoding matrisome regulators (enzymatic regulators and secreted proteins) were similar. Comparison with previous proteomic and transcriptomic data showed that the changes in the matrisome that we described differed markedly from the changes caused by aerobic physical training in young healthy people, in particular, in the expression of the dominant ECM proteins and, especially, in the expression of mRNA of ECM enzymatic regulators and secreted proteins. Comparison of the changes in the expression profiles of these regulatory genes may be useful for identifying pharmacological targets for the prevention of adverse changes/activation of ECM biogenesis under various pathological conditions/physical training.

Transcriptomic and bioinformatic analysis of Histone H2A-genes in Lates calcarifer and Oreochromis niloticus upon Vibrio vulnificus challenge

Histone H2A-derived antimicrobial peptides (AMPs) have been recognized for their antimicrobial properties and role in host defense mechanisms. The present study investigated the transcriptional responses of two histone H2A-derived AMPs, Lc-Histone from Lates calcarifer and GIFT-Histone from Oreochromis niloticus, in response to Vibrio vulnificus infection. The genes encoding these peptides were amplified and sequenced from fingerling stage fishes, followed by in silico analysis and phylogenetic characterization using ClustalW. Computational methods were used to assess their functional attributes, and in vivo bacterial challenge assay was employed to evaluate the efficacy. Sequence alignment identified conserved histone motifs, supporting their evolutionary conservation. The antimicrobial peptide database predicted membrane interaction potential, suggesting antimicrobial activity, alongside biofilm-active properties and efficient expression in heterologous protein systems. Expression profiling of Histone H2A-derived AMP genes under Gram-negative bacterial stimulation revealed distinct temporal dynamics, indicative of their innate immune response involvement. Significant gene expression variations were observed between L. calcarifer and O. niloticus. These baseline findings enhance understanding of host defense mechanisms and bacterial interactions in aquaculture. The antimicrobial potential of histone H2A-derived AMPs highlights their significance as therapeutic agents and warrants further investigation into their mechanisms of action and optimal usage in aquaculture settings.

Microbe-Friendly Plants Enable Beneficial Interactions with Soil Rhizosphere Bacteria by Lowering Their Defense Responses.

The use of plant growth-promoting rhizobacteria presents a promising addition to conventional mineral fertilizer use and an alternative strategy for sustainable agricultural crop production. However, genotypic variations in the plant host may result in variability of the beneficial effects from these plant-microbe interactions. This study examined growth promotion effects of commercial vegetable crop cultivars of tomato, cucumber and broccoli following application with five rhizosphere bacteria. Biochemical assays revealed that the bacterial strains used possess several nutrient acquisition traits that benefit plants, including nitrogen fixation, phosphate solubilization, biofilm formation, and indole-3-acetic acid (IAA) production. However, different host cultivars displayed genotype-specific responses from the inoculations, resulting in significant (p < 0.05) plant growth promotion in some cultivars but insignificant (p > 0.05) or no growth promotion in others. Gene expression profiling in tomato cultivars revealed that these cultivar-specific phenotypes are reflected in differential expressions of defense and nutrient acquisition genes, suggesting that plants can be categorized into "microbe-friendly" cultivars (with little or no defense responses against beneficial microbes) and "microbe-hostile" cultivars (with strong defense responses). These results validate the notion that "microbe-friendly" (positive interaction with rhizosphere microbes) should be considered an important trait in breeding programs when developing new cultivars which could result in improved crop yields.