Gene Expression Signaling Pathways Research Articles

Exploring CK2 transcriptional regulation and signaling pathways in cancer.

e15199 Background: CK2 genes have been implicated in oncogenic processes in different cancer types, and their expression is known to be increased in many cancers relative to their normal tissue types. However the regulation of the three CK2 alpha transcripts and beta transcript is not well understood. Studies investigating the alpha gene ( CSNK2A1) and beta gene ( CSNK2B) found NFκB, ETS1, and SP1 as likely transcription factor regulators in lymphoid and fibroblast cell lines. Our study seeks to explore correlations between CK2 gene expression and the expression of these transcription factors in cancer. Since CK2 also regulates intracellular signaling through pathways such as PI3K-Akt, Jak-Stat, NFkB, Wnt, IL-6, TGF-β, Ras and Notch, this study also seeks to explore the correlation between CK2 expression and gene expression of known downstream signaling pathways across a variety of cancers. Methods: 32 non-overlapping cancer datasets were obtained from the The Cancer Genome Atlas (TCGA) and Broad GDAC Firehose projects which were obtained via cBioPortal.org and analyzed using a combination of cBioportal and RStudio statistical analysis packages. For each cancer type, mRNA expression of each of the four CK2 genes in cancer was compared to expression of transcription factors both previously identified in the literature and predicted generated by TFBIND analysis (via the transcription factor database TRANSFAC R3.4) of the CK2 minimal promoter regions. CK2 gene expression was also compared to expression of genes in known CK2 signaling pathways. Results: Our analysis found CSNK2A1 and CSNK2A3 expression to have a significant, strong positive correlation in nearly all cancer types studied, except pancreatic adenocarcinoma. CSNK2A1 demonstrated significant positive correlation with expression of the transcription factors NFKB1 and c-Rel in lymphoma, thymoma, and other cancers. CSNK2B demonstrated a significant, strong positive correlation with the transcription factors NELFE in every cancer examined. CK2 transcripts also showed significant correlations with other transcription factors and genes involved in IL-6, TGF-β, MAPK, and several other CK2 signaling pathways in many different cancer types. Conclusions: Overall this study demonstrates significant correlations between CK2 gene expression and previously proposed transcriptional regulation mechanisms as well as known CK2 signaling pathways in cancer.

Genetic Insights into Colorectal Cancer: Evaluating PI3K/AKT Signaling Pathway Genes Expression.

The PI3K/AKT pathway plays a pivotal role in cellular processes, and its dysregulation is implicated in various cancers, including colorectal cancer. The present study correlates the expression levels of critical genes (PIK3CA, PTEN, AKT1, FOXO1, and FRAP) in 60 tumor tissues with clinicopathological and demographic characteristics. The results indicate age-related variation in FOXO1 gene expression, with higher levels observed in patients aged 68 and above. In addition, tumors originating from the rectum exhibit higher FOXO1 expression compared to colon tumors, suggesting region-specific differences in expression. The results also identify the potential correlation between PTEN, PIK3CA gene expression, and parameters such as tumor grade and neuroinvasion. The bioinformatic comparative analysis found that PTEN and FOXO1 expressions were downregulated in colorectal cancer tissue compared to normal colon tissue. Relapse-free survival analysis based on gene expression identified significant correlations, highlighting PTEN and FRAP as potential indicators of favorable outcomes. Our findings provide a deeper understanding of the role of the PI3K/AKT pathway in colorectal cancer and the importance of understanding the molecular basis of colorectal cancer development and progression.

Okra extract alleviates lipopolysaccharide-induced inflammation response through the regulation of bile acids, the receptor-mediated pathway, and gut microbiota.

Okra contains flavonoids and vitamin C as antioxidants and it contains polysaccharides as immunomodulators. Flavonoids regulate the inflammatory response in mice and may be related to gut microbiota. This study therefore aimed to investigate the impact of okra extract (OE) on inflammation in mice and to elucidate its underlying mechanism. Forty male Kunming (KM) mice were categorized into four groups: the control (CON) group, the lipopolysaccharide stimulation (LPS) group, the 5 mg mL-1 OE intervention (LPS + OE) group, and the 5 mg mL-1 OE supplementation plus mixed antibiotics (LPS + OE + ABX) group. The results showed that, compared with the OE group, the expression of inflammatory signaling pathway genes was upregulated and gut barrier genes were inhibited in the OE + ABX group. The Fxr receptor was activated and the abundance of Akkermansia was increased after OE supplementation, whereas the effect was reversed in the OE + ABX group. Meanwhile, Fxr was correlated positively with Akkermansia. The OE supplementation alleviated the inflammatory response in mice under LPS stimulation, accompanied by changes in gut microbiota and bile acid receptors, whereas the addition of antibiotics caused a disturbance to the gut microbiota in the OE group, thus reducing the effect of OE in alleviating the inflammatory response. © 2024 Society of Chemical Industry.

Abstract PO1-19-04: Dalpiciclib and tucidinostat in patients with HR+/HER2- advanced breast cancer and resistance to CDK4/6 inhibitors: A phase Ib trial

Abstract Background: Hormone receptor (HR)-positive/epidermal growth factor receptor 2 (HER2)-negative breast cancer accounts for approximately 70% of all breast cancers and is associated with a better prognosis. Estrogen plays an important role in the growth of HR-positive breast cancer, thus patients with this type of tumor are sensitive to hormone inhibitors. However, a quarter of patients will inevitably relapse. Several large clinical trials have demonstrated that the combination of CDK4/6 inhibitors and endocrine therapy (ET) as first or second-line therapy could improve the progression-free survival (PFS) and overall survival for patients with breast cancer. In China, dalpiciclib (a CDK4/6 inhibitor) in combination with fulvestrant has been approved for patients with recurrent or metastatic HR-positive/HER2-negative breast cancer who have failed ET. Moreover, the combination of dalpiciclib and aromatase inhibitors (AI) as an initial treatment for patients with locally advanced or metastatic HR-positive/HER2-negative breast cancer has also been accepted. However, the standard treatment for patients who have failed CDK4/6 inhibitors has not been established. Histone deacetylase (HDAC) inhibitors cause alterations in gene expression in many signaling pathways associated with oncogenesis, leading to the arrest of tumor cell growth and differentiation, as well as promoting tumor apoptosis. Tucidinostat (an HDAC inhibitor) plus AI has been approved for the treatment of locally advanced HR-positive/HER2-negative postmenopausal breast cancer patients who have failed ET. Theoretically, synergistic effects may occur when HDAC inhibitors are combined with CDK4/6 inhibitors. Currently, the clinical data on combination therapy with CDK4/6 inhibitors and HDAC inhibitors have not been reported. Herein, our study aims to explore the efficacy and safety of dalpiciclib and tucidinostat in patients with late-stage HR+/HER2- breast cancer who have failed CDK4/6 inhibitors. Trial Design: The present study is a single-arm, open-label, phase I, dose escalation clinical trial (NCT 05586841). Patients were assigned to four groups to receive either dalpiciclib 125mg/d and tucidinostat 25mg/BIW (group A) or dalpiciclib 125mg/d and tucidinostat 20mg/BIW (group B) or dalpiciclib 100 mg/d and tucidinostat 25mg/BIW (group C) or dalpiciclib 100 mg/d and tucidinostat 20mg/BIW (group D). The Bayesian Optimal Interval (BOIN) design was performed to determine dose-escalation and de-escalation to find the maximum tolerated dose (MTD) of dalpiciclib plus tucidinostat. Key Eligibility Criteria: The study is enrolling female patients who are older than 18 years, with HR-positive/HER2-negative locally recurrent or metastatic breast cancer (MBC), with Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 2. Before entering this trial, all patients must have received ≤1 previous line of chemotherapy for recurrent or MBC, and have failed CDK4/6 inhibitor therapy. Aims: The BOIN design is employed to explore the optimal dose combination of dalpiciclib and tucidinostat and determine recommended doses for a phase II dose expansion clinical trial, based on prespecified dose-limiting toxicity (DLT). Statistical Methods: Safety will be evaluated in the safety set including all patients who received at least one dose of study treatment and underwent at least one safety assessment. Efficacy will be assessed in the full analysis set, defined as all patients who received at least one dose of study treatment. Present and Planned Accrual: Up to 30 participants were planned to be enrolled in the present study. The first participant was enrolled on 18 January 2023. The recruitment is ongoing. Citation Format: Tao Wang, Jinmei Zhou, Xuexue Wu, Zefei Jiang. Dalpiciclib and tucidinostat in patients with HR+/HER2- advanced breast cancer and resistance to CDK4/6 inhibitors: A phase Ib trial [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-19-04.

Baicalin restore intestinal damage after early-life antibiotic therapy: the role of the MAPK signaling pathway

Antibiotic related intestinal injury in early life affects subsequent health and susceptibility. Here, we employed weaned piglets as a model to investigate the protective effects of baicalin against early-life antibiotic exposure-induced microbial dysbiosis. Piglets exposed to lincomycin showed a marked reduction in body weight (p < 0.05) and deterioration of jejunum intestinal morphology, alongside an increase in antibiotic-resistant bacteria such as Staphylococcus, Dolosicoccus, Escherichia-Shigella, and Raoultella. In contrast, baicalin treatment resulted in body weights, intestinal morphology, and microbial profiles that closely resembled those of the control group (p > 0.05), with a significant increase in norank_f_Muribaculaceae and Prevotellaceae_NK3B31_group colonization compared with lincomycin group (p < 0.05). Further analysis through fecal microbial transplantation into mice revealed that lincomycin exposure led to significant alterations in intestinal morphology and microbial composition, notably increasing harmful microbes and decreasing beneficial ones such as norank_Muribaculaceae and Akkermansia (p < 0.05). This shift was associated with an increase in harmful metabolites and disruption of the calcium signaling pathway gene expression. Conversely, baicalin supplementation not only counteracted these effects but also enhanced beneficial metabolites and regulated genes within the MAPK signaling pathway (MAP3K11, MAP4K2, MAPK7, MAPK13) and calcium channel proteins (ORA13, CACNA1S, CACNA1F and CACNG8), suggesting a mechanism through which baicalin mitigates antibiotic-induced intestinal and microbial disturbances. These findings highlight baicalin's potential as a plant extract-based intervention for preventing antibiotic-related intestinal injury and offer new targets for therapeutic strategies.

Dissolved oxygen and ammonia affect ammonia production via GDH/AMPK signaling pathway and alter flesh quality in Chinese perch (Siniperca chuatsi).

The dissolved oxygen (DO) and ammonia are crucial to the growth of Chinese perch (Siniperca chuatsi). Information on the effects of DO and total ammonia nitrogen (TAN) in regulating ammonia nitrogen excretion and flesh quality in Chinese perch is scanty. This study aimed to evaluate the effects of dissolved DO at oxygen levels of 3 mg/L and 9 mg/L, as well as the TAN concentrations of 0.3 mg/L and 0.9 mg/L on ammonia excretion and flesh quality. Results showed that the ammonia contents in plasma, muscle, and liver of the 9 mg/L DO group were significantly higher than those of the 3 mg/L DO group (P < 0.05). However, the expression of AMPK-related signaling pathway genes (gdh, lkb1, and ampd) and flesh quality indicators (gumminess, chewiness, hardness) in the 9 mg/L DO group were significantly lower than those in the 3 mg/L DO group. Under long-term exposure to 0.9 mg/L TAN, the ammonia contents in plasma and gill filaments, as well as muscle flesh quality (resilience, gumminess, chewiness, cohesiveness), were significantly lower than those in the 0.3 mg/L TAN group (P < 0.05). However, the activities of GDH and AMPD enzymes in the 0.9 mg/L TAN group were significantly higher than those in the 0.3 mg/L TAN group. In summary, when fish are exposed to 3 mg/L DO and 0.9 mg/L TAN in the environment for a long time, their amino acids are used for transamination and deamination, resulting in insufficient energy supply for Chinese perch, whereas 9 mg/L DO and 0.9 mg/L TAN caused deterioration of the flesh quality.

MicroRNA miR-285 modulates the metamorphosis in Galeruca daurica by targeting Br-C.

Galeruca daurica has become a new pest on the Inner Mongolia grasslands since an abrupt outbreak in 2009 caused serious damage. As a pupa indicator during insect metamorphosis, the early response gene of the ecdysone signaling pathway, Broad-Complex (Br-C), plays a vital role in the growth and development of insects. MicroRNAs (miRNAs) are small non-coding RNAs which mediate various biological activities, but it is unknown whether and how Br-C is regulated by miRNAs. Temporal expression profiles revealed that miR-285 and Br-C basically displayed an opposite trend during larval-adult development, and Br-C was sharply up-regulated on the last day of final-instar larvae while miR-285 was significantly down-regulated. Both dual-luciferase reporter assay and miRNA-mRNA interaction assay indicated that miR-285 interacts with the coding sequence of Br-C and represses its expression. Not only overexpression but also downexpression of miR-285 led to the failure of larval to pupal to adult metamorphosis. In addition, both overexpression of miR-285 and silence of Br-C inhibited the expression of Br-C and other ecdysone signaling pathway genes, including E74, E75, ECR, FTZ-F1, and HR3. On the contrary, suppressing miR-285 obtained opposite results. Further experiments showed that 20-hydroxyecdysone down-regulated miR-285 and up-regulated Br-C and above-mentioned genes, whereas juvenile hormone alalogue (JHA) resulted in opposite effects. Our results reveal that miR-285 is involved in mediating the metamorphosis in G. daurica by targeting Br-C in the ecdysone signaling pathway. miR-285 and its target Br-C could be as a potential target for G. daurica management. © 2024 Society of Chemical Industry.

The flame retardant triphenyl phosphate alters the epigenome of embryonic cells in an aquatic in vitro model.

Triphenyl phosphate (TPhP) is an organophosphate flame retardant and plasticizer that is added to a wide variety of consumer and industrial products. It is also a ubiquitous environmental pollutant. Exposure to TPhP has been shown to alter gene expression in metabolic and estrogenic signaling pathways in in vitro and in vivo models of a variety of species, and as such, is considered to be an endocrine disrupting chemical. Exposure to endocrine disrupting chemicals is increasingly being associated with changes to the epigenome, especially during embryonic development. The aim of this study was to evaluate whether TPhP exposure in aquatic ecosystems has the ability to alter the epigenome in two immortal cell lines derived from trout (Oncorhynchus mykiss). This study assessed whether 24 h exposure to TPhP resulted in changes to histone modification and DNA methylation profiles in steelhead trout embryonic cells and rainbow trout gill epithelial cells. Results show that several epigenetic modifications on histone H3 and DNA methylation are altered in the embryonic cells following TPhP exposure, but not in the gill epithelial cells. Specifically, histone H3 acetylation, histone H3 mono-methylation and global DNA methylation were found to be reduced. The alterations of these epigenetic modification profiles in the embryonic cells suggest that exposure to TPhP during fetal development may alter gene expression in the developing embryo, likely in metabolic and estrogenic pathways. The impacts to the epigenome determined in this study may even carry multigenerational detrimental effects on human and ecosystem health, which requires further investigation.

Peripheral Blood Mononuclear Cell Gene Expression Associated with Pulmonary Microvascular Perfusion: The Multi-Ethnic Study of Atherosclerosis Chronic Obstructive Pulmonary Disease.

Rationale: Chronic obstructive pulmonary disease (COPD) and emphysema are associated with endothelial damage and altered pulmonary microvascular perfusion. The molecular mechanisms underlying these changes are poorly understood in patients, in part because of the inaccessibility of the pulmonary vasculature. Peripheral blood mononuclear cells (PBMCs) interact with the pulmonary endothelium. Objectives: To test the association between gene expression in PBMCs and pulmonary microvascular perfusion in COPD. Methods: The Multi-Ethnic Study of Atherosclerosis (MESA) COPD Study recruited two independent samples of COPD cases and controls with ⩾10 pack-years of smoking history. In both samples, pulmonary microvascular blood flow, pulmonary microvascular blood volume, and mean transit time were assessed on contrast-enhanced magnetic resonance imaging, and PBMC gene expression was assessed by microarray. Additional replication was performed in a third sample with pulmonary microvascular blood volume measures on contrast-enhanced dual-energy computed tomography. Differential expression analyses were adjusted for age, gender, race/ethnicity, educational attainment, height, weight, smoking status, and pack-years of smoking. Results: The 79 participants in the discovery sample had a mean age of 69 ± 6 years, 44% were female, 25% were non-White, 34% were current smokers, and 66% had COPD. There were large PBMC gene expression signatures associated with pulmonary microvascular perfusion traits, with several replicated in the replication sets with magnetic resonance imaging (n = 47) or dual-energy contrast-enhanced computed tomography (n = 157) measures. Many of the identified genes are involved in inflammatory processes, including nuclear factor-κB and chemokine signaling pathways. Conclusions: PBMC gene expression in nuclear factor-κB, inflammatory, and chemokine signaling pathways was associated with pulmonary microvascular perfusion in COPD, potentially offering new targetable candidates for novel therapies.

Manganese nutrient mitigates ammonia, arsenic toxicity and high temperature stress using gene regulation via NFkB mechanism in fish

The ongoing challenges of climate change and pollution are major factors disturbing ecosystems, including aquatic systems. They also have an impact on gene regulation and biochemical changes in aquatic animals, including fish. Understanding the mechanisms of gene regulation and biochemical changes due to climate change and pollution in aquatic animals is a challenging task. However, with this backdrop, the present investigation was conducted to explore the effects of arsenic (As) and ammonia (NH3) toxicity and high-temperature (T) stress on gene regulation and biochemical profiles, mitigated by dietary manganese (Mn) in Pangasianodon hypophthalmus. The fish were exposed to different combinations of As, NH3, and T, and fed with dietary Mn at 4, 8, and 12 mg kg−1 to evaluate the gene expression of immunity, antioxidative status, cytokine, and NfKB signaling pathway genes. HSP 70, cytochrome P450 (CYP 450), metallothionein (MT), DNA damage-inducible protein (DDIP), caspase (CAS), tumor necrosis factor (TNFα), toll-like receptor (TLR), interleukin (IL), inducible nitric oxide synthase (iNOS), catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) were noticeably highly upregulated by As + NH3 + T stress, whereas Mn diet at 8 mg kg−1 downregulated these genes. Further, total immunoglobulin (Ig), myostatin (MYST), somatostatin (SMT), growth hormone (GH), growth hormone regulator 1 and β, insulin-like growth factors (IGF1X1 and IGF1X2) were significantly upregulated by Mn diets. The biochemical profiles were highly affected by stressors (As + NH3 + T). The bioaccumulation of arsenic in different tissues was also notably reduced by Mn diets. Furthermore, the infectivity of the fish was reduced, and survival against pathogenic bacteria was enhanced by Mn diet at 8 mg kg−1. The results of the present investigation revealed that dietary Mn at 8 mg kg−1 controls gene regulation against multiple stressors (As, NH3, As + NH3, NH3 + T, As + NH3 + T) in fish.

Role of toll-like receptor signaling pathway in a rat model of spinal cord injury: a transcriptomic analysis

Spinal cord injury (SCI) is a debilitating condition characterized by primary and secondary damage to the spinal cord tissue encompassing the site of injury. In this study, we analyzed transcriptomic data from Rattus norvegicus with SCI induced by aneurysm clip impact-compression at seventh thoracic vertebra to explore the main alterations in pathways expression. RNA was extracted from the specific SCI region after 2 weeks and hybridized on Affymetrix GeneChip arrays. Differential gene expression analysis identified 5213 DEGs among which 25 showing a fold change &lt; -2 or &gt; 2. Over-representation analysis was performed using the 25 DEGs above mentioned and revealed the toll-like receptor (TLR) signaling pathway signaling pathway (rno04620) as the only significantly enriched pathway (q-value &lt; 0.05). Further examination of the regulation of this pathway unveiled upregulation of MyD88, Tlr2, and Tlr4, activating NF-κB and MAPK pathways, leading to proinflammatory cytokine synthesis and cellular apoptosis. Upregulation of Cd80 and Cd86 indicated T-cell activation, while IFN-β downstream regulation showed increased expression of JAK-STAT signaling pathway genes. This transcriptomic perspective highlights the dysregulation of the TLR signaling pathway in SCI at 2 weeks and emphasizes its potential role in the pathology.

Low-Temperature Fermented Straw Compost Regulates Rice Growth and Yield by Affecting Soil Physicochemical Properties and the Expression of Important Signaling Pathway Genes

Soil physicochemical properties affect crop growth and yield. The addition of fertilizers can improve the soil quality during crop cultivation, leading to increased agricultural production. Organic fertilizers may be produced by composting straw that would otherwise be discarded as agricultural waste, with potential implications for sustainable agricultural development. However, the mechanism underlying the effects of straw compost on crop growth is unknown. In this study, a microbial agent suitable for straw decomposition in cold regions was used for a large-scale biological fermentation. Organic compost was obtained after the decomposition of straw. The straw compost was mixed with soil in different proportions and then used to cultivate Songjing 2 rice plants. The addition of straw compost significantly increased the growth and yield of the rice plants and enhanced various physiological indices. Moreover, the straw compost treatment significantly improved soil physicochemical properties (e.g., pH, enzyme activity, nutrient composition, and microbial diversity) and optimized the soil conditions for crop growth. In addition, the application of straw compost influenced the expression of genes in rice metabolic pathways as well as pathways mediating secondary metabolite synthesis and plant hormone signal transduction. The study data reflect the potential applicability of low-temperature straw fermentation technology for maximizing crop production.

High gastrointestinal digestive stability endows chondroitin sulfate-soluble undenatured type II collagen complex with high activity: Improvement of osteoarthritis in rats

Previously, we prepared a chondroitin sulfate-soluble undenatured type II collagen complex (CS-SC II) with low salt content. This paper further explored the differences between CS-SC II and SC II in terms of gastrointestinal digestive characteristics and osteoarthritis (OA) improvement. In vitro and in vivo experiments showed that the gastric digestive stability of CS-SC II was high under both pH 2.0 and pH 3.0, the α1 chain and triple helix structure of type II collagen retained >60 %. However, SC II had high gastric digestive stability only under pH 3.0. Furthermore, intestinal digestion had little effect on α1 chains of CS-SC II and SC II, and distribution experiments showed that they might exert their biological activities in the intestine. CS-SC II had obvious improvement in OA rats at 1.0 mg/kg/d, that is, the joint swelling was significantly reduced and the weight-bearing ratio of the right hind limb was increased to 49 %, which was close to that of 4.0 mg/kg/d SC II. The wear of articular cartilage, Mankin and OARSI scores of rats in CS-SC II group were significantly reduced. The effects of low-dose CS-SC II on the proportion of regulatory T cells (Treg), mRNA expression of OA key biomarkers (Il6, Ccl7, MMP-3 and MMP13) and signaling pathway genes (NF-κB, AKT or AMPKα) were comparable to those of high-dose SC II. These results showed that CS-SC II might have greater potential to improve OA at a lower dose than SC II due to its high gastrointestinal digestive stability at a wide range of pH conditions.

Red and Blue Light Induce Soybean Resistance to Soybean Mosaic Virus Infection through the Coordination of Salicylic Acid and Jasmonic Acid Defense Pathways.

Soybean mosaic virus (SMV) seriously harms soybean quality and yield. In order to understand the effect of a heterogeneous light environment on the disease resistance of intercropped soybeans, we simulated three kinds of light environments to learn the effects of white light, blue light, and far-red light on the SMV resistance of soybeans. The results showed that compared with the control, SMV-infected soybeans showed dwarfing and enhanced defense. The symptoms of leaves under red and blue light were less severe than those under white light, the virus content of infected plants was about 90% lower than under white light, the activity of antioxidant enzymes increased, and the accumulation of reactive oxygen species decreased. The oxidation damage in SMV-infected soybeans was serious under far-red light. Transcriptome data showed that the biostimulatory response, plant-pathogen interaction, and plant hormone signaling pathway gene expression of SMV-infected soybeans were significantly up-regulated under red light compared with the control. Compared with the control, the genes in the biostimulatory response, calcium ion binding, carbohydrate-binding, mitogen-activated protein kinase (MAPK) signaling, and plant-pathogen interaction pathways, were significantly up-regulated in SMV-infected soybeans under blue light. In far-red light, only 39 genes were differentially expressed in SMV-infected soybeans compared with the control, and most of the genes were down-regulated. Compared with the control, the up-regulation of the salicylic acid (SA) pathway defense gene in SMV-infected soybeans under red light was higher than under other light treatments. Compared with the control, the up-regulation of the jasmonic acid (JA) and ethylene (ET) pathway defense genes in SMV-infected soybeans under blue light was higher than under other light treatments. Compared with the control, most defense-related genes in the SA and JA pathways were inhibited in SMV-infected soybeans under far-red light, while genes in the ET pathway were significantly up-regulated. These results will advance our understanding of the disease resistance mechanism of intercropping soybeans in a heterogeneous light environment and provide new ideas for the prevention and control of viral diseases.

GL13K-modified titanium regulates osteogenic differentiation via the NF-κB pathway

The osteoimmune response plays a crucial regulatory role in the osseointegration of dental implants. Previous studies found the antimicrobial peptide coating (GL13K) could activate the immunomodulatory potential of macrophages (Raw 264.7) and promote osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). To further investigate the mechanism of interaction between immunomodulation and differentiation, a co-culture model of the representative cells (Raw 264.7 and BMSCs) was constructed to mimic the immune microenvironment. In this system, GL13K coating of titanium implant effectively inhibited the polarization of the inflammatory M1 type and promoted the polarization of the anti-inflammatory M2 type. Furthermore, the inhibited NF-κB signaling pathway and Mip-2 gene expression were found and validated by bioinformatics analysis and virus-induced gene silencing, which significantly affected the tissue repair process. It can be concluded that the GL13K coating had the potential to establish a localized immune microenvironment conducive to osteogenic differentiation through cellular interactions. Subsequent investigations would be dedicated to a thorough examination of the osseointegration effects of GL13K coating.

Длинная некодирующая РНК NEAT1_1 снижает выживаемость первичных нейронных клеток при ЭПР-стрессе

NEAT1 long non-coding RNAs play an important role in the central nervous system (CNS) and are associated with a number of pathological conditions. Increased levels of NEAT1 in the brain have been observed in neurodegenerative and psychiatric diseases — the significance of such an increase is still poorly understood. Functionally, NEAT1 is associated with cellular stress pathways in the nervous system. The aim of the current study was to evaluate the effect of increased levels of the short isoform NEAT1_1 on survival of mice primary hippocampal cultures under ER-stress induced by MG132 proteasome inhibitor. Primary cultures were obtained from transgenic animals expressing human NEAT1_1. Cellular composition and apoptosis were assessed using immunocytochemical staining. The expression of apoptosis signaling pathway genes was analyzed by quantitative PCR with reverse transcription. No differences in cellular composition and morphological characteristics of neurons were observed in primary neuronal cultures obtained from transgenic animals as compared to wild type cultures. Induction of ER-stress resulted in a more significant increase in apoptotic death of cells including neurons in NEAT1_1 expressing cultures in comparison with the wild type cultures. ER-stress signaling pathway genes Atf4 and Ddit3 were less expressed in transgenic cultures under stress. Expression of Bcl2l2 and Mcl1 anti-apoptotic genes was reduced as well. Thus, high levels of NEAT1_1 in primary neuronal cultures increased apoptotic cell death under ER-stress.

Effect of aqueous extract of Millettia speciosa Champ on intestinal health maintenance and immune enhancement of Cyprinus carpio

Millettia speciosa Champ (MSP) is a natural Chinese herb that improves gastrointestinal health and enhances animal immunity. An 8-week feeding trial with different MSP levels (0, 150, 300, and 600 mg/kg) was conducted to evaluate the promotive effects of MSP in Cyprinus carpio. Results indicate that MSP improved intestinal immunity to some extent evidenced by the immuno-antioxidant parameters and the 16S rRNA in the Illumina MiSeq platform. With the analysis of transcriptome sequencing, 4685 differentially expressed genes (DEGs) were identified, including 2149 up-regulated and 2536 down-regulated. According to the GO and KEGG enrichments, DEGs were mainly involved in the immune system. Transcriptional expression of the NOD-like signaling pathway and key genes retrieved from the transcriptome database confirmed that innate immunity was improved in response to dietary MSP administration. Therefore, MSP could be used as a feed supplement that enhances immunity. This may provide insight into Chinese herb additive application in aquaculture production.

Abstract 15521: Wnt Signaling Inhibition Prevents Postnatal Inflammation and Disease Progression in Congenital Myxomatous Valve Disease

Introduction: Myxomatous valve disease (MVD) is the most common cause of mitral regurgitation, leading to cardiac dysfunction and heart failure. MVD in a mouse model of Marfan syndrome (MFS) includes valve leaflet thickening and increased immune cell infiltration. However, the underlying mechanisms by which immune cells are recruited in MFS valves remain undefined. Hypothesis: Inhibition of Wnt signaling prevents MVD progression in MFS valves. Methods: Mice with the Fibrillin 1 variant Fbn1 C1039G/+ recapitulate histopathological features of MFS and Wnt signaling activity was detected in TCF/Lef-lacZ reporter mice. Single-cell RNA sequencing was performed from mitral valves of WT and Fbn1 C1039G/+ mice at 1 month-of-age. Inhibition of Wnt signaling was achieved by conditional induction of Wnt inhibitor Dkk1 in valve interstitial cells of Fbn1 C1039G/+ ; Periostin-Cre; tetO-Dkk1; R26-rtTA mice. Dietary doxycycline was administered for 1 month beginning with MVD initiation (1-month-old) or MVD progression (2-month-old). Histological evaluation and immunofluorescence for immune cells were performed. Results: Wnt signaling pathway gene expression is activated early in mitral valve disease progression, prior to immune cell infiltration in Fbn1 C1039G/+ mice. Single cell transcriptomics revealed similar mitral valve cell heterogeneity between WT and Fbn1 C1039G/+ mice at 1 month-of-age. Wnt ligands and responsive genes were predominantly increased in valve interstitial cells and valve endothelial cells of Fbn1 C1039G/+ mice. Inhibition of Wnt signaling by Dkk1 induction at 1 month-of-age prevented the initiation of MVD as indicated by reduced valve leaflet thickness with decreased CD45+ leukocytes and CCR2+ immune cells in Fbn1 C1039G/+ mice. However, later Wnt inhibition starting at 2 months when inflammation and myxomatous changes are occurring did not prevent the progression of MVD. Conclusions: Wnt signaling is involved in the initiation of mitral valve abnormalities and inflammation, but is not responsible for valve disease progression once it has been initiated. Thus, Wnt signaling inhibition prevents initiation of congenital MVD, which provides a promising therapeutic target for the early treatment of congenital MVD.

Physiological and molecular mechanisms of Acacia melanoxylon stem in response to boron deficiency.

Boron is an essential micronutrient for plant growth as it participates in cell wall integrity. The growth and development of Acacia melanoxylon stem can be adversely affected by a lack of boron. To explore the mechanism of boron deficiency in A. melanoxylon stem, the changes in morphological attributes, physiological, endogenous hormone levels, and the cell structure and component contents were examined. In addition, the molecular mechanism of shortened internodes resulting from boron deficiency was elucidated through transcriptome analysis. The results showed that boron deficiency resulted in decreased height, shortened internodes, and reduced root length and surface area, corresponding with decreased boron content in the roots, stems, and leaves of A. melanoxylon. In shortened internodes of stems, oxidative damage, and disordered hormone homeostasis were induced, the cell wall was thickened, hemicellulose and water-soluble pectin contents decreased, while the cellulose content increased under boron deficiency. Furthermore, plenty of genes associated with cell wall metabolism and structural components, including GAUTs, CESAs, IRXs, EXPs, TBLs, and XTHs were downregulated under boron deficiency. Alterations of gene expression in hormone signaling pathways comprising IAA, GA, CTK, ET, ABA, and JA were observed under boron deficiency. TFs, homologous to HD1s, NAC10, NAC73, MYB46s, MYB58, and ERF92s were found to interact with genes related to cell wall metabolism, and the structural components were identified. We established a regulatory mechanism network of boron deficiency-induced shortened internodes in A. melanoxylon based on the above results. This research provides a theoretical basis for understanding the response mechanism of woody plants to boron deficiency.

Antifungal mechanism of Bacillus amyloliquefaciens SC-B15 and its application in cereal mildewproof and grape preservation

Microorganisms and their metabolites play vital roles in inhibiting the growth of toxic-producing fungi. Here, Bacillus amyloliquefaciens SC-B15 showed over 64% inhibition of six mycotoxin-producing fungi and the best inhibition of A. ochraceus (81%). Meanwhile, the supernatant fraction of >10 kDa showed the best inhibition against A. ochraceus and the antifungal proteins were probably cell wall hydrolytic enzymes. Our study showed that the antifungal components lead to the destruction of mycelium and spores of A. carbonarius, while also affecting gene expression of cell wall integrity signaling pathways and secondary metabolic processes, such as leading to substantial downregulation of pks genes and affecting the synthesis of OTA precursors. The antifungal fraction could markedly reduce the spot diameter (66.19%) and Ochratoxin A (OTA) accumulation (63.56%) of grape wounds, and reduce A. carbonarius growth (64.78%) and OTA accumulation (84.41%) during cereal storage. Our research indicates that the SC-B15 strain has a promising prospect in the control of Aspergillus and OTA contamination.