Much attention has been paid to the public health crisis that has resulted from the opioid epidemic. Given the high number of opioid users that are of childbearing age, the impact of utero exposure is a serious concern. Unfortunately, there is little knowledge regarding the consequences of opioid exposure during early development. While neurobehavioral effects of opioid exposure are well-documented, effects of exposure on embryogenesis remain largely unexplored. To address this gap in knowledge, we investigated the effects of oxycodone and fentanyl exposure on gene expression in zebrafish (Danio rerio) embryos using whole embryo RNA sequencing. Embryos were exposed to environmentally relevant (oxycodone HCl 10.6 ng/L and fentanyl citrate 0.629 ng/L) and therapeutically relevant doses (oxycodone HCl 35.14 μg/L and fentanyl citrate 3.14 μg/L) from 2 to 24 h post-fertilization (hpf), followed by another 24 h of opioid-free development. mRNA profiling at 48 hpf revealed dose- and drug-specific gene expression changes. Lower doses of oxycodone and fentanyl both induced more differentially expressed transcripts (DETs) than higher doses, potentially indicative of opioid receptor desensitization occurring at higher concentrations. In total, 892 DETs (corresponding to 866 genes) were identified across all conditions suggesting continued differential gene expression well after cessation of opioid exposure. Gene ontology analysis revealed changes in gene expression relating to extracellular matrix (ECM) organization, cell adhesion, and visual and nervous system formation. Key pathways include those involved in axon guidance, synapse formation, and ECM biosynthesis/remodeling, all of which have potential implications on neural connectivity and sensory development. These findings demonstrate that very early developmental exposure to opioids induces persistent transcriptomic changes which may have lasting implications for vertebrate cellular functions. Overall, these data provide insights into the molecular mechanisms of opioid-induced alterations during development.

It is known that nutrient deprivation following detachment can cause non-chilling peel pitting (NCPP) in citrus fruits when stored under a non-stressful environment and that this damage is reduced by pretreating the fruit with ethylene (ETH) (4 d, 10 µL L-1). The present work investigates the effect of this pretreatment on jasmonate (JA) accumulation and transcriptional regulation in mature Navelate oranges (Citrus sinensis L. Osbeck) stored under non-stressful conditions. ETH increased the expression of abundant genes participating in the synthesis of cis-(+)-12-oxo-phytodienoic acid (OPDA), jasmonic acid (JA), and methyl jasmonate (MeJA). ETH also upregulated genes involved in jasmonoyl-isoleucine (JAIle) synthesis (CsJAR1) and decrease (CsCYP94B3 and CYP94C1), and CsSTA2, related to JA sulfation. The levels of these JA metabolites increased during fruit holding in ETH and after shifting them to air, with MeJA accumulation being especially remarkable. Overall, the beneficial effect of ETH on reducing NCPP appears to be related not only to this redirection of OPDA and JA metabolism towards the formation of JA derivatives but also to the regulation of JA signalling. Indeed, the repression of the receptor CsCOI1 and upregulation of various CsJAZs repressors caused by nutrient deprivation, together with the ETH-mediated induction of CsCOI1, CsTOPLESS, and abundant CsJAZs during long-term storage, suggests the occurrence of an ETH-enhanced negative transcriptional regulatory feedback loop in JA metabolism and signalling, by which the susceptibility of detached Navelate oranges to NCPP might be reduced.

Pancreatic ductal adenocarcinoma (PDAC) accounts for 90% of all pancreatic malignancies. Despite the remarkable improvement concerning treatment, late detection and resistance to clinically used chemotherapeutic agents remain major challenges. Trichostatin A (TSA), a histone deacetylase inhibitor, has been recognized as an effective therapeutic agent against PDAC by inhibiting proliferation, inducing apoptosis, and sensitizing PDAC cells to chemotherapeutic agents such as gemcitabine. Microgravity has become a useful tool in cancer research due to its effects on various cellular processes. This paper presents a deep molecular and proteomic analysis investigating cell growth, the modulation of cytokeratins, and proteins related to apoptosis, cellular metabolism, and protein synthesis after TSA treatment in simulated microgravity (SMG)-exposed PaCa44 3D cells. Our analysis concerns the effects of TSA treatment on cell proliferation: the impairment of the cell cycle with the downregulation of proteins involved in Cdc42 signaling and G1/G2- and G2/M-phase transitions. Thus, we observed modification of survival pathways and proteins related to autophagy and apoptosis. We also observed changes in proteins involved in the regulation of transcription and the repair of damaged DNA. TSA treatment promotes the downregulation of some markers involved in the maintenance of the potency of stem cells, while it upregulates proteins involved in the induction and modulation of the differentiation process. Our data suggest that TSA treatment restores the cell phenotype prior to simulated microgravity exposure, and exerts an intriguing activity on PDAC cells by reducing proliferation and inducing cell death via multiple pathways.

Photothermal therapy combines the effects of near-infrared laser (NIR laser) and strong light-absorbing materials to combat pathogens and unwanted biofilms. Graphene derivatives have a negative effect on microorganisms, and the combination of NIR laser irradiation and carbon nanomaterials (CNMs) can enhance their antibacterial effect. This investigation is devoted to the determination of the expression level of bacterial stress response genes (soxS and rpoS) under graphene oxide (GO), reduced graphene oxide (rGO), and NIR laser irradiation (1270 nm). GO, rGO and NIR laser irradiation separately and irradiation in the presence of graphene derivatives cause an increase in the expression level of rpoS associated with the general stress response of bacteria. GO and rGO do not change the expression level of soxS associated with the cell response to oxidative stress, and decrease it in the presence of a strong oxidizing agent paraquat (PQ). The expression of soxS increases under laser irradiation, but decreases under NIR laser irradiation in combination with graphene derivatives. The effect of GO, rGO, and NIR laser irradiation on the formation and eradication of E. coli biofilms was studied. NIR laser with GO and rGO suppresses the metabolic rate and decreases the intracellular ATP content by 94 and 99.6%, respectively. CNMs are shown to reduce biofilm biomass and the content of extracellular polymeric substances (EPSs), both exopolysaccharides and protein in the biofilm matrix. Graphene derivatives in combination with NIR laser irradiation may be an effective means of combating emerging and mature biofilms of Gram-negative bacteria.

Highly differentiated tissues and organs play essential biological functions in multicellular organisms. Coordination of organ developmental process with tissue differentiation is necessary to achieve proper development of mature organs, but mechanisms for such coordination are not well understood. We used cotyledon margin cells from Arabidopsis plant as a new model system to investigate cell elongation and cell division during organ growth and found that margin cells endured a developmental phase transition from the "elongation" phase to the "elongation and division" phase at the early stage in germinating seedlings. We also discovered that the stem cell factors BARELY ANY MERISTEM 1 (BAM1) and WUSCHEL-related homeobox1 (WOX1) are involved in the regulation of margin cell developmental phase transition. Furthermore, exogenous auxin treatment (1 nanomolar,nM) promotes cell division, especially longitudinal cell division. This promotion of cell division did not occur in bam1 and wox1 mutants. Based on these findings, we hypothesized a new "moderate auxin concentration" model which emphasizes that a moderate auxin concentration is the key to triggering the developmental transition of meristematic cells.

Cannabidiol (CBD) has shown promise in treating cancers with an inflammatory microenvironment. Although it has been demonstrated that IL-1β induces epithelial-mesenchymal transition (EMT) of MCF-7 cells and CBD reverts this process, in restoring the epithelial non-invasive phenotype, there is limited understanding of how this cannabinoid regulates these processes. In this work, MCF-7 cells were induced to adopt an aggressive phenotype (6D cells), which was reversed by CBD. Then, protein expression was analyzed by mass spectrometry to compare 6D vs. MCF-7 cells and 6D+CBD vs. 6D cells proteomes. Novel proteins associated with EMT and CBD signaling were identified. Twenty-four of them were oppositely regulated by IL-1β and CBD, suggesting new points of crosstalk between the IL-1β and CBD signaling pathways. From the data, two protein networks were constructed: one related to EMT with 58 up-regulated proteins and another with 21 related to CBD signaling. The first one showed the proteins BRCA1, MSN, and CORO1A as the key axis that contributes to the establishment of a mesenchymal phenotype. In the CBD signaling, the key axis was formed by SUPT16H, SETD2, and H2BC12, which suggests epigenetic regulation by CBD in the restoration of an epithelial phenotype of breast cancer cells, providing new targets for anticancer therapy.

Cu is a chemical contaminant that is toxic to aquatic animals at certain concentrations. The present study describes the gill transcriptome, proteome, and histology of the Chinese mitten crab (Eriocheir sinensis) subjected to copper stress. Female 14-month-old E. sinensis (n = 60) crabs (79.6 ± 4.8 g, body weight) were randomly divided into two groups and subjected to copper stress at concentrations of 0 μg/L (Blank group, GBL) and 50 μg/L (Copper group, GCP) for 96 h. In total, 278 upregulated and 189 downregulated differentially expressed genes (DEGs) were identified in the GBL and GCP groups. In addition, upregulated and downregulated differentially expressed proteins (DEPs) in the GBL and GCP groups were 260 and 308, respectively. An integrated analysis demonstrated that the three DEGs overlapped between the two omics approaches. Comparative omics analysis indicated that seven GO terms were significantly (p < 0.05) enriched by overlapping DEGs in the transcriptome and proteome. Further analysis revealed that only one overlapping DEG (stumps) was enriched in two common KEGG pathways, the PI3K-Akt and B cell receptor signaling pathways. Histological analyses showed that copper-stressed gills had collapsed lamellae with enlarged marginal vessels and shortened interlamellar spaces due to the disruption of the pillar cells and cuticles. These results demonstrate the variations in copper-stressed gills and will be helpful for better understanding the mechanisms of copper toxicity in E. sinensis.

In recent years, copper pollution has gradually become one of the major problems of soil environmental pollution. Lignin plays an important role in plant resistance to biotic and abiotic stresses. CCoAOMT is a key enzyme in the lignin biosynthesis process. In this study, the CCoAOMT gene family members of Platycodon grandiflorus were identified by bioinformatics methods, and their basic characteristics and potential functions were analyzed. The results showed that five members of the PgCCoAOMT gene family were identified in P. grandiflorus, with protein lengths ranging from 246 to 635 amino acids, and were evenly distributed on four chromosomes. Phylogenetic analysis indicated that the PgCCoAOMT gene family was divided into two subclades, namely Clade1a, Clade1b, Clade1c, Clade1d, and Clade2. The cis-regulatory element analysis of the promoter revealed that the PgCCoAOMT members contained a large number of cis-regulatory elements responsive to stress, and conjecture PgCCoAOMT2, PgCCoAOMT4, and PgCCoAOMT5 were involved in the lignin synthesis. The qRT-PCR results showed that, within 5 days of copper stress treatment, except for the PgCCoAOMT4 gene, the other genes exhibited different expression levels. Furthermore, the expression levels of all five PgCCoAOMT genes increased significantly at 7 days of treatment. With the increase in the number of days of treatment, the content of lignin in the seedings of P. grandiflorus showed a trend of increasing first and then decreasing under copper stress. In general, in the copper stress treatment of 1-3 days, the transcriptional inhibition of PgCCoAOMT1 and PgCCoAOMT3 and the increase in lignin content contradicted each other, suggesting that there was post-translational activation or alternative metabolic pathways compensation. Meanwhile, in the 7-day treatment, the coordinated up-regulation of the genes was accompanied by the failure of lignin synthesis, which pointed to the core bottleneck of metabolic precursors depletion and enzyme activity inactivation caused by root damage. Research objective: This study reveals the expression level of the PgCCoAOMT gene in the seedings of P. grandiflorus under copper stress, providing a theoretical basis for elucidating the mechanism of P. grandiflorus response to copper stress and for subsequent improvement of root resistance in P. grandiflorus.

Lung adenocarcinoma (LUAD) is a leading cause of cancer-related mortality, with heme metabolism playing a critical role in tumor progression and treatment resistance. This study investigates the clinical implications of heme metabolism in LUAD, focusing on its link to ferroptosis and drug sensitivity. Using multi-omics data from TCGA-LUAD, GEO databases, and a single-cell RNA-seq cohort, we identified two molecular subtypes based on heme metabolism-related genes. We further developed a prognostic panel, termed the heme metabolism risk score (HMRS), using LASSO and multivariate Cox regression analyses. The HMRS panel effectively stratified patients into high- and low-risk groups, with high-risk patients showing enhanced tumor proliferation, suppressed ferroptosis, and resistance to chemotherapy. Single-cell analysis revealed elevated heme metabolism risk in epithelial cells correlated with tumor progression. Drug sensitivity predictions were validated in platinum-based chemotherapy cohorts, confirming HMRS as a robust prognostic tool. ABCC2 was identified as a key regulator of ferroptosis and cisplatin resistance, with in vitro experiments demonstrating that ABCC2 knockdown enhanced cisplatin-induced ferroptosis. These findings highlight HMRS as a critical tool for patient stratification and ABCC2 as a promising therapeutic target to overcome cisplatin resistance.

Colorectal cancer remains a significant global health concern. In this study, we investigated the anticancer potential of Circaea mollis Siebold & Zucc. (CS&Z), a traditional medicinal plant known for its anti-inflammatory, anti-arthritic, and antioxidant properties, in the treatment of colorectal cancer. We found that CS&Z induces apoptosis and G1/S phase cell cycle arrest in colorectal cancer cells, primarily through the suppression of the proto-oncogene c-Myc. Specifically, the depletion of RPL5, a ribosomal protein associated with c-Myc regulation, reversed the suppression of c-Myc by CS&Z. Additionally, when co-administered with the standard chemotherapeutic agents doxorubicin and 5-fluorouracil, CS&Z demonstrated synergistic effects, thereby further emphasizing its potential efficacy as a therapeutic option for the treatment of colorectal cancer. Moreover, the constituents of CS&Z, detected through liquid chromatography-mass spectrometry analysis, reportedly exhibit anticancer activities. Taken together, our findings suggest that CS&Z holds promise as a natural product capable of modulating oncogenic signaling in colorectal cancer and may serve as a complementary agent in future therapeutic strategies.

Barium (Ba) is classified as a non-essential element, meaning that it does not play a requisite role in the physiological processes of living organisms, but it poses a significant health risk to them. Plants that grow in Ba-rich soils, particularly near barite outcrops or mining waste, often accumulate high levels of Ba. Excess Ba in plant cells can lead to the overproduction of reactive oxygen species (ROS), which contributes to oxidative stress. Typically, nitric oxide (NO) can help alleviate heavy metal stress; however, under certain conditions, elevated levels of superoxide and nitric oxide may result in nitrosative and nitrative stress. This study investigated whether exposing barley plants to barium acetate (300 μM and 600 μM) triggers a nitro-oxidative response in spring barley plants. The molecular and biochemical analyses revealed fluctuations in the gene expression and activity of antioxidant enzymes and a steady rise in hydrogen peroxide (H2O2) in the leaves. Lower Ba concentrations and shorter exposures increased NO levels, while higher concentrations and more prolonged exposure reduced them, affecting nitrogen metabolism. These findings highlight the toxicological risks posed by Ba, especially for cultivated plants, and underscore the need for further research on its impact on plant physiology and the potential risks to human health.

Cervical cancer ranks as the fourth most prevalent cancer and cause of cancer-related mortality among women globally. It exhibits a recurrence/metastasis rate of approximately 30% and a dismal 5-year survival of only 17% in metastatic cases. Despite significant advancements in surgical techniques, chemoradiotherapy, and targeted therapies, effective treatment options for metastatic cervical cancer remain limited. This study explored Polyphyllin I (PPI), which is a monomeric compound derived from the Rhizoma of Paris Polyphyllin, as a potential inhibitor of cervical cancer metastasis. Mechanistically, PPI directly interacted with β-catenin at the Ser552 site, inhibiting its phosphorylation and subsequent nuclear translocation, thereby suppressing TCF/LEF transcriptional activity and downstream EMT transcription factors (ZEB1, Slug, Snail, and Twist). Notably, PPI promoted β-catenin degradation via the autophagy-lysosomal pathway, as confirmed by CHX chase assays and the detection of the p62 and LC3 proteins, without altering the mRNA levels of β-catenin. In vitro experiments demonstrated that PPI effectively suppressed the migration and invasion of HO-8910PM cells by reversing the process of EMT. Additionally, PPI effectively inhibited TCF/LEF signaling, leading to a reduction in the transcription levels of EMT-associated transcription factors (EMT-TFs), which was mediated by the TCF/LEF family downstream of β-catenin. Furthermore, PPI exhibited inhibitory effects on proliferation, migration, and invasion in both HPV-positive (SiHa) and HPV-negative (C33A) cervical cancer cells. In vivo, PPI significantly suppressed peritoneal metastasis in a luciferase-labeled HO-8910PM xenograft mouse model. These findings reveal the dual role of PPI in blocking β-catenin signaling and inducing β-catenin depletion, thereby effectively restraining metastatic progression. This study underscores the potential of PPI as a promising therapeutic candidate for targeting cervical cancer metastasis through autophagy-mediated β-catenin regulation, offering a novel strategy to address current treatment limitations.

Sex-related differences in the structure and function of the adrenal cortex in mature rats are well recognized, largely driven by the action of sex hormones on the hypothalamic-pituitary-adrenal axis (HPA). By replacing testosterone or estradiol in gonadectomized rats, we aimed to elucidate the regulation of micro RNA (miRNA) profiles by sex hormones and their role in physiological adrenal function, providing new insights into gene expression modulation in the adrenal gland. This paper focuses on the description of miRNA profiles using the microarray technique. In our study, we observed significant sex differences in miRNA and mRNA expression levels. These differences are as follows: miRNA expression profiles Male C vs. Female C-0 down, 25 up-regulated, while mRNA profiles were 43 down and 27 up-regulated. Moreover, we observed the most significant differences in miRNA profiles between orchiectomized male rats supplemented with testosterone (ORX + T) and ovariectomized female rats treated with estradiol (OVX + E). Furthermore, we described changes in target gene expression and biological processes regulated by miRNAs. The processes most differentially expressed between the ORX + T and OVX + E groups are those related to the metabolism and synthesis of sterol compounds, the positive and negative regulation of metabolic processes in cells, e.g., cholesterol metabolism, response to various external factors, e.g., hormones, regulation of processes related to cell motility. We also identified several miRNAs, such as miR-370, miR-377, and miR-503, that exhibited interesting changes in their expression after testosterone or estradiol replacement. These results contribute to a deeper understanding of adrenal physiology.

Giardiasis is a common intestinal infection caused by Giardia lamblia. The standard treatment for this parasitic infection involves the administration of nitroimidazoles, albendazoles, and nitrothiazoles. However, in recent years, Giardia lamblia strains resistant to these treatments have been reported. Additionally, the current therapies exhibit considerable side effects, highlighting the need for new compounds that specifically target this parasite. The aim of this study was to evaluate nitrothiazole analogs and assess their impact on the metabolic, redox, and structural gene expression of this parasite. First, the compounds CNZ-7, CNZ-8, FLP-2, FLP-6, and FLP-8 were tested at concentrations ranging from 0 to 50 µM to determine their IC50 in G. lamblia cultures. Subsequently, gene expression changes and structural cell damage in trophozoites were analyzed following incubation with the IC50 of each compound. The giardicidal activity of the compounds was also evaluated in a nitazoxanide-resistant strain. The results showed that FLP-2, FLP-6, and FLP-8 exhibited a stronger effect on trophozoite viability compared to nitazoxanide (NTZ) and metronidazole (MTZ). Both compounds induced an increase in the expression of phosphofructokinase (PFK), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), pyruvate kinase (PK), pyruvate phosphate dikinase (PPDK), and pyruvate:ferredoxin oxidoreductase (PFOR). Additionally, FLP-2 caused ultrastructural alterations in trophozoites. Furthermore, FLP-2, FLP-6, and FLP-8 demonstrated efficacy against drug-resistant strains. These findings suggest that FLP-2, FLP-6, and FLP-8 are promising candidates for the treatment of giardiasis, as they effectively reduce parasite viability, modify gene expression, and exhibit activity against drug-resistant G. lamblia strains.

This study aims to investigate the endogenous gibberellin levels and related genes analysis of noxious invasive weed Heracleum sosnowskyi. Genome-wide identification, phylogenetic analysis, conserved motif analysis, and gene structure characterization of GA-oxidases were performed. We analysed endogenous GAs levels and the expression of target HsGAoxs in response to GA3 within H. sosnowskyi developing ovaries. Twenty-seven HsGAoxs genes were identified, distributed across eleven chromosomes. Phylogenetic analysis classified proteins into the HsGA20ox, C19-HsGA2ox, and HsGA3ox subfamilies, facilitating functional predictions. Among the thirteen HsGA2ox protein members, there were no C20-GA2ox subfamily that distinguish H. sosnowskyi from other model plant species. The analysis of gene structure and conserved motifs confirmed the phylogenetic grouping and suggested that the evolutionary pattern was maintained within these subfamilies. The observed increase in precursor and bioactive GA levels provides evidence that they play a crucial role in promoting fruit growth. Ovary phenotypes reflected the timing of peak gibberellin levels, specifically during the cell expansion period. Exogenous GA3 treatment promoted HsGA3ox1 expression within both the central and lateral regions of the umbel ovaries. Overall, the results show that GA levels are precisely regulated by multiple HsGAox genes for stable early fruit development, and that disturbances in this stability affect fruit development. This opens up the possibility of investigating the role of GA in H. sosnowskyi fruit formation and developing measures for invasion control.

Soil heavy metal pollution by chromium (Cr) and copper (Cu) is a global environmental concern.

Cardiovascular disorders (CVDs) are the leading cause of mortality worldwide, highlighting an urgent need for innovative therapeutic strategies. Recent advancements highlight the potential of naturally derived bioproducts with epigenetic properties to offer protection against CVDs. These compounds act on key epigenetic mechanisms, DNA methylation, histone modifications, and non-coding RNA regulation to modulate gene expression essential for cardiovascular health. This review explores the effects of various bioproducts, such as polyphenols, flavonoids, and other natural extracts, on these epigenetic modifications and their potential benefits in preventing and managing CVDs. We discuss recent discoveries and clinical applications, providing insights into the epigenetic regulatory mechanisms of these compounds as potential epidrugs, naturally derived agents with promising therapeutic prospects in epigenetic therapy for CVDs.

The increasing global incidence of breast cancer calls for the identification of new therapeutic targets and the assessment of possible neem-derived inhibitors by means of computational modeling and integrated genomic research.

Hatchery fumigation is recognized as a crucial step to control microbial bloom in the environment, and formaldehyde is one of the most widely used disinfectants to ensure successful hatchability and healthy production. While many of the benefits are thought to be derived from disinfectant properties, it is possible that additional host gene and genetic pathway modulation could contribute to these outcomes. The current study aimed to capture the in ovo transcriptional response of liver tissue to formaldehyde treatment.

PEIG-1/GPRC5A (phorbol ester induced gene-1/G-protein Coupled Receptor Class C Group 5 Member A) was the first identified member of the orphan G protein-coupled receptor family GPRC5. Deregulation of its expression is associated with the development and progression of various types of tumours, particularly colon carcinoma. In this work, we study the effects of vitamin D (VD, cholecalciferol) and retinoic acid (RA) on GPRC5A mRNA expression in the colorectal cancer cell lines Caco-2 and T84. Both VD (10 µM) and all-trans retinoic acid (ATRA, atRA, RA) (10 µM) increased GPRC5A mRNA levels. Protein kinase C (PKC) inhibition with Gö6983 (10 µM) completely abolished the effects of VD and RA on GPRC5A expression. In parallel, VD and RA increased cytosolic and mitochondrial ROS levels (cROS and mtROS). However, the antioxidants NAC (10 mM) and MitoTEMPO (10 µM) raised GPRC5A gene expression levels in the presence of VD or RA, suggesting that elevated ROS may inhibit GPRC5A expression. In conclusion, both VD and RA stimulate GPRC5A expression. The mechanisms involve a common and essential PKC signalling pathway, as Gö6983 inhibited both VD- and RA-induced signalling.