Search Results (8,608)

Sex-based immunological differences significantly influence the outcome of vaccination, yet the molecular mediators underpinning these differences remain largely elusive. MicroRNAs (miRNAs), key post-transcriptional regulators of gene expression, have emerged as critical modulators of innate and adaptive immune responses. In this study, we investigated the expression profile of selected circulating miRNAs as potential biomarkers of sex-specific humoral responses to the mRNA COVID-19 vaccine in a cohort of health care workers. Plasma samples were collected longitudinally at a defined time point (average 71 days) post-vaccination and analyzed using RT-qPCR to quantify a panel of immune-relevant miRNAs. Anti-spike (anti-S) IgG titers were measured by chemiluminescent immunoassays. Our results revealed sex-dependent differences in miRNA expression dynamics, with miR-221-3p and miR-148a-3p significantly overexpressed in vaccinated female HCWs and miR-155-5p overexpressed in vaccinated males. MiR-148a-3p showed a significant association with anti-S/RBD (RBD: receptor binding domain) IgG levels in a sex-specific manner. Bioinformatic analysis for miRNA targets indicated distinct regulatory networks and pathways involved in innate and adaptive immune responses, potentially underlying the differential immune activation observed between males and females. These findings support the utility of circulating miRNAs as minimally invasive biomarkers for monitoring and predicting sex-specific vaccine-induced immune responses and provide mechanistic insights that may inform tailored vaccination strategies. Full article

To minimize the deleterious effects of oxidative stress and improve oocyte competence, we assessed the impact of melatonin during in vitro pre-maturation (pre-IVM) in bovine cumulus–oocyte complexes (COCs). We compared three groups: control (conventional IVM), pre-IVM control (without melatonin), and pre-IVM + MTn (with melatonin). The analyses included levels of reactive oxygen species (ROS), mitochondrial activity, oocyte lipid content, and the expression of genes related to oxidative stress and lipid metabolism in oocytes and cumulus cells. We also examined embryo quality by evaluating kinetics of development and gene expression. The pre-IVM + MTn group exhibited an increase (p ≤ 0.05) in ROS levels and a decrease (p ≤ 0.05) in lipid content, while maintaining mitochondrial activity similar (p > 0.05) to that of the control group. Regarding gene expression, the effect of pre-IVM, independent of melatonin, was characterized by a decrease in FABP3 transcripts in cumulus cells and reductions in GSS and NFE2L2 transcripts in oocytes (p ≤ 0.05). The pre-IVM + MTn group also displayed a decrease (p ≤ 0.05) in CAT and SOD2 transcript levels. In terms of embryonic development, the pre-IVM + MTn group achieved a higher blastocyst rate on D7 (p ≤ 0.05) compared to the control group (30.8% versus 25.8%), but with similar rates (p > 0.05) to the pre-IVM control group (30.8% versus 35.9%). However, there was a decrease in the levels of the PLAC8 transcript. This study indicates that, under the conditions tested, melatonin did not significantly benefit oocyte competence. Full article

Mesenchymal stem cells (MSCs), i.e., adult stem cells with immunomodulatory and secretory properties, contribute to tissue growth and regeneration, including healing processes. Some metal nanoparticles (NPs) are known to exhibit antimicrobial activity and may further potentiate tissue healing. We studied the effect of Ag, CuO, and ZnO NPs after in vitro exposure of mouse MSCs at the transcriptional level in order to reveal the potential toxicity as well as modulation of other processes that may modify the activity of MSCs. mRNA–miRNA interactions were further investigated to explore the epigenetic regulation of gene expression. All the tested NPs mediated immunomodulatory effects on MSCs, generation of extracellular vesicles, inhibition of osteogenesis, and enhancement of adipogenesis. Ag NPs exhibited the most pronounced response; they impacted the expression of the highest number of mRNAs, including those encoding interferon-γ-stimulated genes and genes involved in drug metabolism/cytochrome P450 activity, suggesting a response to the potential toxicity of Ag NPs (oxidative stress). Highly interacting MiR-126 was upregulated by all NPs, while downregulation of MiR-92a was observed after the ZnO NP treatment only, and both effects might be associated with the improvement of MSCs’ healing potency. Overall, our results demonstrate positive effects of NPs on MSCs, although increased oxidative stress caused by Ag NPs may limit the therapeutical potential of the combined MSC+NP treatment. Full article

Transcription factors play crucial roles in regulating gene expression, and any dysregulation in their levels could be involved in cancer progression. The role of androgen receptors (AR) and zinc finger (ZNF) proteins in tumors, like prostate cancer (PC), remains poorly understood. Moreover, due to the multifaceted transcriptional behavior of ARs and ZNFs, their biological role in cancer progression may also depend on the interplay with micro-RNAs (miRNAs). Based on The Cancer Genome Atlas (TCGA) database, we analyzed the expression levels of zinc finger transcripts and ARs in PC. Specifically, exploring their involvement in cancer progression and regulation by miRNAs. The analysis relied on several tools to create a multivariate combination of the original biomarkers to improve their diagnostic efficacy. Multidimensional Scaling (MDS) identified two new dimensions that were entered into a regression analysis to determine the best predictors of overall survival (OS) and disease-free interval (DFI). A combination of both dimensions predicted almost 50% (R² = 0.46) of the original variance of OS. Kaplan–Meier survival analysis also confirmed the significance of these two dimensions regarding the clinical output. This study showed preliminary evidence that several transcription factor expression levels belonging to the zinc family and related miRNAs can effectively predict patients’ overall PC survivability. Full article

Background: Severe damage to one side of the brain often leads to adverse consequences and can also cause widespread changes throughout the brain, especially in the contralateral area. Studying molecular changes in the contralateral cerebral hemisphere, especially with regard to genetic regulation, can help discover potential treatment strategies to promote recovery after severe brain trauma on one side. Methods: In our study, the right motor cortex was surgically removed to simulate severe unilateral brain injury, and changes in glial cells and synaptic structure in the contralateral cortex were subsequently assessed through immunohistological, morphological, and Western blot analyses. We conducted transcriptomic studies to explore changes in gene expression levels associated with the inflammatory response. Results: Seven days after corticotomy, levels of reactive astrocytes and hypertrophic microglia increased significantly in the experimental group, while synapsin-1 and PSD-95 levels in the contralateral motor cortex increased. These molecular changes are associated with structural changes, including destruction of dendritic structures and the encapsulation of astrocytes by synapses. Genome-wide transcriptome analysis showed a significant increase in gene pathways involved in inflammatory responses, synaptic activity, and nerve fiber regeneration in the contralateral cortex after corticorectomy. Key transcription factors such as NF-κB1, Rela, STAT3 and Jun were identified as potential regulators of these contralateral changes. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) confirmed that the mRNA expression levels of Cacna1c, Tgfb1 and Slc2a1 genes related to STAT3, JUN, and NF-κB regulation significantly increased in the contralateral cortex of the experimental group. Conclusions: After unilateral brain damage occurs, changes in the contralateral cerebral hemisphere are closely related to processes involving inflammation and synaptic function. Full article

The rhizosphere microbiome plays an important role in carbon- and nitrogen-cycling in soil and in the stress response of plants. It also affects the function of the ammonium transporter (AmtB) that senses nitrogen levels inside and outside the cells of the associative nitrogen-fixing bacterium GXGL-4A. However, the potential mechanism of the interaction between the AmtB deletion mutant of GXGL-4A (∆amtB) and microorganisms in the rhizosphere of plants under low-nitrogen stress is still unclear. As revealed by transcriptome analyses, mutation of the amtB gene in GXGL-4A resulted in a significant up-regulation of many functional genes associated with nitrogen fixation and transportation at transcription level. The application of ∆amtB changed the nitrogen level in the rhizosphere of cucumber seedlings and reshaped the microbial community structure in the rhizosphere, enriching the relative abundance of Actinobacteriota and Gemmatimonadota. Based on bacterial functional prediction analyses, the metabolic capacities of rhizobacteria were improved after inoculation of cucumber seedlings with the original strain GXGL-4A or the ∆amtB mutant, resulting in the enhancement of amino acids, lipids, and carbohydrates in the cucumber rhizosphere, which promoted the growth of cucumber plants under a low-nitrogen stress condition. The results contribute to understanding the biological function of gene amtB, revealing the regulatory role of the strain GXGL-4A on cucumber rhizosphere nitrogen metabolism and laying a theoretical foundation for the development of efficient nitrogen-fixing bacterial agents for sustainable agricultural production. Full article

Melanoma is a highly aggressive skin cancer with limited therapeutic response. Targeting intracellular signaling pathways and promoting tumor cell differentiation are promising therapeutic strategies. Pentoxifylline (PTX) and norcantharidin (NCTD) have demonstrated antitumor properties, but their combined mechanisms of action in melanoma remain poorly understood. The effects of PTX (30 and 60 mg/kg) and NCTD (0.75 and 3 mg/kg), administered alone or in combination, in a DBA/2J murine B16-F1 melanoma model via intraperitoneal and intratumoral (IT) routes were evaluated. Tumor growth was monitored, and molecular analyses included RNA sequencing and immunofluorescence quantification of PI3K, AKT1, mTOR, ERBB2, BRAF, and MITF protein levels, and molecular docking simulations were performed. In the final stage of the experiment, combination therapy significantly reduced tumor volume compared to monotherapies, with the relative tumor volume decreasing from 18.1 ± 1.2 (SD) in the IT Control group to 0.6 ± 0.1 (SD) in the IT combination-treated group (n = 6 per group; p < 0.001). RNA-seq revealed over 3000 differentially expressed genes in intratumoral treatments, with enrichment in pathways related to oxidative stress, immune response, and translation regulation (KEGG and Reactome analyses). Minimal transcript-level changes were observed for BRAF and PI3K/AKT/mTOR genes; however, immunofluorescence showed reduced total and phosphorylated levels of PI3K, AKT1, mTOR, BRAF, and ERBB2. MITF protein levels and pigmentation increased, especially in PTX-treated groups, indicating enhanced melanocytic differentiation. Docking analyses predicted direct binding of both drugs to PI3K, AKT1, mTOR, and BRAF, with affinities ranging from −5.7 to −7.4 kcal/mol. The combination of PTX and NCTD suppresses melanoma progression through dual mechanisms: inhibition of PI3K/AKT/mTOR signaling and promotion of tumor cell differentiation. Full article

Elodea nuttallii is a significant submerged macrophyte utilized in shrimp and crab aquaculture, yet it exhibits low thermotolerance. This study investigated the physiological responses and transcriptomic characteristics of E. nuttallii under high-temperature stress (HTS). The results indicated that HTS significantly reduced the absolute growth rate (AGR) and photosynthetic efficiency of E. nuttallii while concurrently elevating antioxidant enzyme activities, malondialdehyde (MDA) content, and concentrations of osmotic adjustment compounds. Furthermore, the apical segments of E. nuttallii demonstrated greater sensitivity to HTS compared to the middle segments. Under exposure to 35 °C and 40 °C, antioxidant enzyme activities, MDA content, and osmotic adjustment compound levels were significantly higher in the apical segments than in the middle segments. Transcriptomic analysis revealed 7526 differentially expressed genes (DEGs) in the apical segments at 35 °C, a number substantially exceeding that observed in the middle segments. Enrichment analysis of DEGs revealed significant upregulation of key metabolic regulators under HTS, including carbohydrate metabolism genes (HXK, FRK) and phenylpropanoid biosynthesis enzymes (4CL, COMT). This transcriptional reprogramming demonstrates E. nuttallii’s adaptive strategy of modulating carbon allocation and phenolic compound synthesis to mitigate thermal damage. Our findings not only elucidate novel thermotolerance mechanisms in aquatic plants but also provide candidate genetic targets (HXK, 4CL) for molecular breeding of heat-resilient cultivars through transcriptomic screening. Full article

Cadmium (Cd) is a toxic environmental heavy metal that exerts harmful effects on multiple tissues, including the kidney, liver, lung, and bone, and is also associated with the development of anemia. However, the precise molecular mechanisms underlying Cd-induced toxicity remain incompletely understood. In this paper, we review the recent molecular mechanisms of Cd-induced toxicity and its modification, with a particular emphasis on our recent findings. Using a combination of DNA microarray analysis, protein–DNA binding assays, and siRNA-mediated gene silencing, we identified several transcription factors, YY1, FOXF1, ARNT, and MEF2A, as novel molecular targets of Cd. The downregulation of their downstream genes, including UBE2D2, UBE2D4, BIRC3, and SLC2A4, was directly associated with the expression of cytotoxicity. In addition, PPARδ plays a pivotal role in modulating cellular susceptibility to Cd-induced renal toxicity, potentially by regulating apoptosis-related signaling pathways. In addition to apoptosis pathways, Cd toxicity through ROS generation, ferroptosis and pyroptosis were summarized. Furthermore, it has been revealed that Cd suppresses the expression of iron transport-related genes in duodenal epithelial cells leading to impaired intestinal iron absorption as well as decreased hepatic iron levels. These findings provide a mechanistic basis for Cd-induced iron deficiency anemia, implicating disrupted iron homeostasis as a contributing factor. Full article

Furunculosis caused by Aeromonas salmonicida poses a significant challenge to the sustainable production of maraena whitefish (Coregonus maraena). This case report outlines a multi-year disease management strategy at a European whitefish facility with two production departments, each specialising in different life-cycle stages. Recurrent outbreaks of A. salmonicida necessitated the development of effective vaccination protocols. Herd-specific immersion vaccines failed to confer protection, while injectable formulations with plant-based adjuvants caused severe adverse reactions and mortality rates exceeding 30%. In contrast, the bivalent vaccine Alpha Ject 3000, containing inactivated A. salmonicida and Vibrio anguillarum with a mineral oil adjuvant, yielded high tolerability and durable protection in over one million whitefish. Post-vaccination mortality remained low (3.3%), aligning with industry benchmarks, and furunculosis-related losses were fully prevented in both departments. Transcriptomic profiling of immune-relevant tissues revealed distinct gene expression signatures depending on vaccine type and time post-vaccination. Both the herd-specific vaccine and Alpha Ject 3000 induced the expression of immunoglobulin and inflammatory markers in the spleen, contrasted by reduced immunoglobulin transcript levels in the gills and head kidney together with the downregulated expression of B-cell markers. These results demonstrate that an optimised injectable vaccination strategy can significantly improve health outcomes and disease resilience in maraena whitefish aquaculture. Full article

To elucidate the molecular mechanisms underlying anther abortion in celery male sterile lines, this study investigates the morphological differences of floral organs and differential gene expression patterns between two lines at the flowering stage. Using the male sterile line of celery ‘QCBU-001’ and the fertile line ‘Jinnan Shiqin’ as materials, anther structure was analyzed by paraffin sections, and related genes were detected using transcriptome sequencing and qRT-PCR. The results indicated that the anther locules were severely shrunken at maturity in the sterile lines. The callose deficiency led to abnormal development of microspores, preventing the formation of mature pollen grains and ultimately leading to complete anther abortion. The transcriptome results revealed that 3246 genes were differentially expressed in sterile and fertile lines, which were significantly enriched in pathways such as starch and sucrose metabolism and phenylpropanoid biosynthesis. Additionally, differential expression patterns of transcription factor families (MYB, bHLH, AP2, GRAS, and others) suggested their potential involvement in regulating anther abortion. Notably, the expression level of callose synthase gene AgGSL2 was significantly downregulated in sterile anthers, which might be an important cause of callose deficiency and pollen sterility. This study not only provides a theoretical basis for elucidating the molecular mechanism underlying male sterility in celery but also lays a foundation for the utilization and improvement of male sterile lines in vegetable hybrid breeding. Full article

Proanthocyanidins are a subclass of flavonoids formed through a poorly understood polymerization process that forms chains of 3–30 catechins and epi-catechins. Proanthocyanidins serve as UV protectants and antifeedants that accumulate in diverse plant species, including the lotus. To identify candidate genes underlying proanthocyanidin synthesis and polymerization, we generated and functionally annotated transcriptomes from seedpods and seed epicarps of two lotus cultivars, “Guoqing Hong” and “Space Lotus”, which accumulate markedly divergent proanthocyanidin levels across the immature, near-mature, and mature developmental stages. Our transcriptome analysis was based on a total of 262.29 GB of raw data. We aligned the transcriptome data with the lotus genome and obtained an alignment efficiency that ranged from 91.74% to 96.44%. Based on the alignment results, we discovered 4774 new genes and functionally annotated 3232 genes. A total of 14,994 differentially expressed genes (DEGs) were identified from two-by-two comparisons of transcript libraries. We found 61 DEGs in the same developmental stage in the same tissue of different species. Comparative transcriptome analysis of seedpods and seed epicarps from two cultivars identified 14,994 differentially expressed genes (DEGs), of which 10 were functionally associated with proanthocyanidin synthesis and 9 were possibly implicated in the polymerization reactions. We independently quantified the expression of the candidate genes using qRT-PCR. Significant differences in the expression of candidate genes in different tissues and periods of lotus species are consistent with particular genes contributing to the polymerization of catechins and epi-catechins into proanthocyanidins in lotus seedpods and seed epicarps. Full article

Microalgae, with their unparalleled capabilities for sunlight-driven growth, CO₂ fixation, and synthesis of diverse high-value compounds, represent sustainable cell factories for a circular bioeconomy. However, industrial deployment has been hindered by biological constraints and the inadequacy of conventional genetic tools. The advent of CRISPR-Cas systems initially provided precise gene editing via targeted DNA cleavage. This review argues that the true transformative potential lies in moving decisively beyond cutting to harness CRISPR as a versatile synthetic biology “Swiss Army Knife”. We synthesize the rapid evolution of CRISPR-derived tools—including transcriptional modulators (CRISPRa/i), epigenome editors, base/prime editors, multiplexed systems, and biosensor-integrated logic gates—and their revolutionary applications in microalgal engineering. These tools enable tunable gene expression, stable epigenetic reprogramming, DSB-free nucleotide-level precision editing, coordinated rewiring of complex metabolic networks, and dynamic, autonomous control in response to environmental cues. We critically evaluate their deployment to enhance photosynthesis, boost lipid/biofuel production, engineer high-value compound pathways (carotenoids, PUFAs, proteins), improve stress resilience, and optimize carbon utilization. Persistent challenges—species-specific tool optimization, delivery efficiency, genetic stability, scalability, and biosafety—are analyzed, alongside emerging solutions and future directions integrating AI, automation, and multi-omics. The strategic integration of this CRISPR toolkit unlocks the potential to engineer robust, high-productivity microalgal cell factories, finally realizing their promise as sustainable platforms for next-generation biomanufacturing. Full article

Perturbations in the tightly regulated processes of VLDL biosynthesis and secretion can directly impact both liver and cardiovascular health. Patients with metabolic disorders have an increased risk of developing hepatic steatosis, which can lead to cirrhosis. These associated metabolic risks underscore the importance of discerning the role of different cellular proteins involved in VLDL biogenesis, transport, and secretion. Small VCP-Interacting Protein (SVIP) has been identified as a component of VLDL transport vesicles and VLDL secretion. This study evaluates the cellular effects stemming from the CRISPR-Cas9-mediated depletion of SVIP in rat hepatocytes. The SVIP-knockout (KO) cells display an increased VLDL retention with elevated intracellular levels of ApoB100 and neutral lipid staining. RNA sequencing studies reveal an impaired PPARα and Nrf2 signaling in the SVIP KO cells, implying a state of metabolic reprograming, with a shift from fatty acid uptake, synthesis, and oxidation to cells favoring the activation of glucose by impaired glycogen storage and increased glucose release. Additionally, SVIP KO cells exhibit a transcriptional profile indicative of acute phase response (APR) in hepatocytes. Many inflammatory markers and genes associated with APR are upregulated in the SVIP KO hepatocytes. In accordance with an APR-like response, the cells also demonstrate an increase in mRNA expression of genes associated with protein synthesis. Together, our data demonstrate that SVIP is critical in maintaining hepatic lipid homeostasis and metabolic balance by regulating key pathways such as PPARα, Nrf2, and APR. Full article

It is believed that caspases may play a significant role in the development of cancer, and the expression levels of genes encoding these proteins may influence the prognosis and clinical course of cancer. Taking into account the information presented, we examined the expression profiles of 11 genes from the caspase family in patients diagnosed with triple-negative breast cancer (TNBC). We qualified 29 patients with TNBC. A fragment of the tumor and a fragment of normal tissue surrounding the tumor were collected from each patient. Then, RNA was isolated, and the reverse transcription process was performed. The expression levels of caspase family genes were determined using the real-time PCR method. The obtained data were correlated with clinical data and compared with data from the Cancer Genome Atlas database using the Breast Cancer Gene Expression Miner v4.8 and Ualcan. Based on the results of the conducted research, it can be assumed that the levels of expression of caspase family genes may be correlated with the clinical course of cancer in patients with TNBC, and further research may indicate that profiling the expression levels of these genes may be used in selecting personalized treatment methods. Full article