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12 pages, 1193 KiB

Open AccessArticle

Establishment and Optimization of an Experiment System for Flow Cytometry in Oil-Seed Camellia

by Ying Zhang, Zhen Zhang, Xiangnan Wang, Rui Wang, Zhilong He, Gaohong Xiao, Weiguo Li and Yongzhong Chen

Horticulturae 2024, 10(7), 704; https://doi.org/10.3390/horticulturae10070704 - 3 Jul 2024

Viewed by 185

Abstract

Ploidy identification is a basic method for determining germplasm resources and for breeding new varieties of oil-seed camellia. In this study, flow cytometry and K-mer analysis were used to identify the ploidy of oil-seed camellia germplasms. To determine the best tissue organ type, lysis time, and dyeing time, evaluation indices such as the presence of a clear main peak, the ease of sampling, and the coefficient of variation were used. A technique was established, and the ploidies of different oil-seed camellia germplasms were identified. The results showed that pollen was the best material and that using a 400 mL PI lysis solution for 10 min lysis, followed by dyeing with a 1600 mL DAPI dyeing solution for 10 min, was the most suitable technique. According to the peak value of the control diploid Camellia azalea, 15 samples were estimated to be diploid, 24 samples were tetraploid, 18 samples were hexaploid, and 13 samples were octoploid. In addition, the K-mer analysis results showed that among the five samples, CK, C051, and C047 were diploid, while C037 and C043 were tetraploid, results that are consistent with the results of the flow cytometry identification. This study is therefore valuable for the polyploid selection and use of different ploidy germplasm resources for the cross breeding of oil-seed camellia. Full article

(This article belongs to the Section Genetics, Genomics, Breeding, and Biotechnology (G2B2))

15 pages, 11771 KiB

Open AccessEssay

Harmonic Self-Compensation Control for Bidirectional Grid Tied Inverter Based on Crown Porcupine Optimization Algorithm

by Ao Tian, Fenghui Zhang and Peng Xiao

Electronics 2024, 13(13), 2607; https://doi.org/10.3390/electronics13132607 - 3 Jul 2024

Viewed by 154

Abstract

A self-compensating control strategy for harmonic parameters based on the crown porcupine optimization algorithm is proposed for the single-phase rectifier and two-phase inverter operation mode of the bidirectional converter. In order to improve the response speed of the inverter voltage, the instantaneous expressions of the phase angle coefficient and amplitude coefficient of the dc-side voltage doubling fluctuation are derived, and the third harmonic is calculated based on the crown porcupine optimization algorithm according to the Proportional Integral (PI) + Quasi-Proportional Resonance (QPR) double closed-loop control method and injected into the input voltage of the inverter side to offset the influence of the bus-doubling fluctuation on the output voltage of the two-phase inverters of B and C so that the total harmonic content of the two-phase output voltages of the two-phase inverters of B and C can be reduced. The total harmonic content of the B and C inverter output voltages is reduced. The effective control of the control method for single-phase rectifier two-phase inverter mode is verified through simulation. Finally, the effectiveness of the control strategy is verified by experimenting with a 15 kW LCL-type bi-directional converter prototype. Full article

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21 pages, 5789 KiB

Open AccessArticle

Activation and Autoinhibition Mechanisms of NLR Immune Receptor Pi36 in Rice

by Yang Yang, Liu Tan, Xingzhe Xu, Qiaoyi Tang, Ji Wang, Shiyue Xing, Rui Wang, Ting Zou, Shiquan Wang, Jun Zhu, Shuangcheng Li, Yueyang Liang, Qiming Deng and Ping Li

Int. J. Mol. Sci. 2024, 25(13), 7301; https://doi.org/10.3390/ijms25137301 - 2 Jul 2024

Viewed by 461

Abstract

Nucleotide-binding and leucine-rich repeat receptors (NLRs) are the most important and largest class of immune receptors in plants. The Pi36 gene encodes a canonical CC-NBS-LRR protein that confers resistance to rice blast fungal infections. Here, we show that the CC domain of Pi36 plays a role in cell death induction. Furthermore, self-association is required for the CC domain-mediated cell death, and the self-association ability is correlated with the cell death level. In addition, the NB-ARC domain may suppress the activity of the CC domain through intramolecular interaction. The mutations D440G next to the RNBS-D motif and D503V in the MHD motif autoactivated Pi36, but the mutation K212 in the P-loop motif inhibited this autoactivation, indicating that nucleotide binding of the NB-ARC domain is essential for Pi36 activation. We also found that the LRR domain is required for D503V- and D440G-mediated Pi36 autoactivation. Interestingly, several mutations in the CC domain compromised the CC domain-mediated cell death without affecting the D440G- or D503V-mediated Pi36 autoactivation. The autoactivate Pi36 variants exhibited stronger self-associations than the inactive variants. Taken together, we speculated that the CC domain of Pi36 executes cell death activities, whereas the NB-ARC domain suppressed CC-mediated cell death via intermolecular interaction. The NB-ARC domain releases its suppression of the CC domain and strengthens the self-association of Pi36 to support the CC domain, possibly through nucleotide exchange. Full article

(This article belongs to the Section Molecular Plant Sciences)

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19 pages, 3816 KiB

Open AccessArticle

The Prognostic and Therapeutic Potential of Fragile X Mental Retardation 1 (FMR1) Gene Expression in Prostate Adenocarcinoma: Insights into Survival Outcomes and Oncogenic Pathway Modulation

by Salem Baldi, Bushra Amer, Fawze Alnadari, Maged AL-Mogahed, Yaqin Gao and Yaser Gamallat

Int. J. Mol. Sci. 2024, 25(13), 7290; https://doi.org/10.3390/ijms25137290 - 2 Jul 2024

Viewed by 294

Abstract

Prostate adenocarcinoma (PRAD) is the second most common tumor associated with death. The role and mechanisms of the fragile X mental retardation 1 (FMR1) gene in PRAD remain unknown. We conducted an analysis of FMR1 expression in PRAD to determine its prognostic importance and connection to carcinogenic pathways such as PI3K_AKT_mTOR. Survival analyses were utilized to establish a correlation between FMR1 expression and patient outcomes. We used the integration of genomic data with bioinformatic predictions to predict the regulatory factors of the FMR1 gene in PRAD. Our data revealed that individuals with higher levels of FMR1 expression experience worse survival outcomes compared to those with lower expression (hazard ratio [HR] = 5.08, 95% confidence interval [CI] = 1.07 – 24, p = 0.0412). FMR1 expression was significantly higher in patients with advanced pathological tumor stages, particularly in the pT3 and pT4 combined stages and the pN1 nodal stage. Furthermore, patients with high Gleason scores (GSs) (combined GSs 8 and 9) exhibited increased levels of FMR1 expression. Our results further identify a possible regulatory link between FMR1 and key oncogenic pathways, including PI3K_AKT_mTOR, and predict the possible mechanism by which FMR1 is regulated in PRAD. Our data suggest that the FMR1 gene could serve as a biomarker for PRAD progression. However, in-depth investigations, including those with large patient samples and in vitro studies, are needed to validate this finding and understand the mechanisms involved. Full article

(This article belongs to the Special Issue Molecular Research on Prostate Cancer)

16 pages, 5455 KiB

Open AccessArticle

Fatty Acid Amides Suppress Proliferation via Cannabinoid Receptors and Promote the Apoptosis of C6 Glioma Cells in Association with Akt Signaling Pathway Inhibition

by Nágila Monteiro da Silva, Izabella Carla Silva Lopes, Adan Jesus Galué-Parra, Irlon Maciel Ferreira, Chubert Bernardo Castro de Sena, Edilene Oliveira da Silva, Barbarella de Matos Macchi, Fábio Rodrigues de Oliveira and José Luiz Martins do Nascimento

Pharmaceuticals 2024, 17(7), 873; https://doi.org/10.3390/ph17070873 - 2 Jul 2024

Viewed by 283

Abstract

A glioma is a type of tumor that acts on the Central Nervous System (CNS) in a highly aggressive manner. Gliomas can occasionally be inaccurately diagnosed and treatments have low efficacy, meaning that patients exhibit a survival of less than one year after diagnosis. Due to factors such as intratumoral cell variability, inefficient chemotherapy drugs, adaptive resistance development to drugs and tumor recurrence after resection, the search continues for new drugs that can inhibit glioma cell growth. As such, analogues of endocannabinoids, such as fatty acid amides (FAAs), represent interesting alternatives for inhibiting tumor growth, since FAAs can modulate several metabolic pathways linked to cancer and, thus, may hold potential for managing glioblastoma. The aim of this study was to investigate the in vitro effects of two fatty ethanolamides (FAA1 and FAA2), synthetized via direct amidation from andiroba oil (Carapa guianensis Aublet), on C6 glioma cells. FAA1 and FAA2 reduced C6 cell viability, proliferation and migratory potential in a dose-dependent manner and were not toxic to normal retina glial cells. Both FAAs caused apoptotic cell death through the loss of mitochondrial integrity (ΔΨm), probably by activating cannabinoid receptors, and inhibiting the PI3K/Akt pathway. In conclusion, FAAs derived from natural products may have the potential to treat glioma-type brain cancer. Full article

(This article belongs to the Special Issue Therapeutic Agents for the Treatment of Tumors in the CNS)

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13 pages, 2330 KiB

Open AccessArticle

G-Protein Coupled Receptor 1 Is Involved in Tetrachlorobisphenol A-Induced Inflammatory Response in Jurkat Cells

by Xiaoyu Lu, Mengjie Yu, Yingxin Yang, Xiaolan Zhang, Tian Chen and Bingli Lei

Toxics 2024, 12(7), 485; https://doi.org/10.3390/toxics12070485 - 2 Jul 2024

Viewed by 269

Abstract

Estrogens can affect the immune inflammatory response through estrogen receptor alpha (ERα), but the specific role of estrogen member receptor G-protein coupled receptor 1 (GPER1) in this process remains unclear. In this study, we evaluated the effects of tetrachlorobisphenol A (TCBPA), which has estrogen activity, on immune inflammatory-related indicators of Jurkat cells, as well as investigated the role of GPER1 in these effects. The results showed that TCBPA at lower concentrations significantly promoted the viability of Jurkat cells, whereas higher concentrations decreased cell viability. TCBPA at concentrations ranging from 1 to 25 μM increased the intracellular reactive oxygen species (ROS) levels. Additionally, treatment with 10 μM TCBPA increased the protein expression of ERα and GPER1, elevated the phosphorylation of protein kinase B (p-Akt), and upregulated the mRNA levels of GPER1, Akt, and phosphoinositide 3-kinase (PI3K) genes. Treatment with 10 μM TCBPA also upregulated the protein or gene expression of pro-inflammatory cytokines, such as interleukins (IL1β, IL2, IL6, IL8, IL12α) and tumor necrosis factor alpha (TNFα) in Jurkat cells. Furthermore, pretreatment with a GPER1 inhibitor G15 significantly reduced the mRNA levels of Akt induced by 10 μM TCBPA. Moreover, the upregulation of mRNA expression of RelA (p65), TNFα, IL6, IL8, and IL12α induced by 10 μM TCBPA was also significantly attenuated after G15 pretreatment. These findings suggest that TCBPA upregulates the expression of genes related to inflammatory responses by activating the GPER1-mediated PI3K/Akt signaling pathway. This study provides new insights into the mechanism of TCBPA-induced inflammatory response. Full article

(This article belongs to the Special Issue Occurrence and Environmental Risks of Organic Pollutants in Aquatic Environment)

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15 pages, 5974 KiB

Open AccessArticle

A PNPLA3-Deficient iPSC-Derived Hepatocyte Screen Identifies Pathways to Potentially Reduce Steatosis in Metabolic Dysfunction-Associated Fatty Liver Disease

by Caren Doueiry, Christiana S. Kappler, Carla Martinez-Morant and Stephen A. Duncan

Int. J. Mol. Sci. 2024, 25(13), 7277; https://doi.org/10.3390/ijms25137277 - 2 Jul 2024

Viewed by 406

Abstract

The incidence of nonalcoholic fatty liver disease (NAFLD), or metabolic dysfunction-associated fatty liver disease (MAFLD), is increasing in adults and children. Unfortunately, effective pharmacological treatments remain unavailable. Single nucleotide polymorphisms (SNPs) in the patatin-like phospholipase domain-containing protein (PNPLA3 I148M) have the most significant genetic association with the disease at all stages of its progression. A roadblock to identifying potential treatments for PNPLA3-induced NAFLD is the lack of a human cell platform that recapitulates the PNPLA3 I148M-mediated onset of lipid accumulation. Hepatocyte-like cells were generated from PNPLA3⁻^/⁻ and PNPLA3^I148M/M-induced pluripotent stem cells (iPSCs). Lipid levels were measured by staining with BODIPY 493/503 and were found to increase in PNPLA3 variant iPSC-derived hepatocytes. A small-molecule screen identified multiple compounds that target Src/PI3K/Akt signaling and could eradicate lipid accumulation in these cells. We found that drugs currently in clinical trials for cancer treatment that target the same pathways also reduced lipid accumulation in PNPLA3 variant cells. Full article

(This article belongs to the Special Issue Recent Research in Stem Cells to Organoids)

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23 pages, 2058 KiB

Open AccessReview

Indole-3-Carbinol and Its Derivatives as Neuroprotective Modulators

by Alka Ashok Singh, Dhananjay Yadav, Fazlurrahman Khan and Minseok Song

Brain Sci. 2024, 14(7), 674; https://doi.org/10.3390/brainsci14070674 - 2 Jul 2024

Viewed by 306

Abstract

Brain-derived neurotrophic factor (BDNF) and its downstream tropomyosin receptor kinase B (TrkB) signaling pathway play pivotal roles in the resilience and action of antidepressant drugs, making them prominent targets in psychiatric research. Oxidative stress (OS) contributes to various neurological disorders, including neurodegenerative diseases, stroke, and mental illnesses, and exacerbates the aging process. The nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant responsive element (ARE) serves as the primary cellular defense mechanism against OS-induced brain damage. Thus, Nrf2 activation may confer endogenous neuroprotection against OS-related cellular damage; notably, the TrkB/phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathway, stimulated by BDNF-dependent TrkB signaling, activates Nrf2 and promotes its nuclear translocation. However, insufficient neurotrophin support often leads to the downregulation of the TrkB signaling pathway in brain diseases. Thus, targeting TrkB activation and the Nrf2-ARE system is a promising therapeutic strategy for treating neurodegenerative diseases. Phytochemicals, including indole-3-carbinol (I3C) and its metabolite, diindolylmethane (DIM), exhibit neuroprotective effects through BDNF’s mimetic activity; Akt phosphorylation is induced, and the antioxidant defense mechanism is activated by blocking the Nrf2-kelch-like ECH-associated protein 1 (Keap1) complex. This review emphasizes the therapeutic potential of I3C and its derivatives for concurrently activating neuronal defense mechanisms in the treatment of neurodegenerative diseases. Full article

(This article belongs to the Special Issue Role of Inflammation, Oxidative Stress, and Metabolic Dysfunction in Neurodegenerative Diseases: Pharmacological Targets and Therapeutic Interventions)

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22 pages, 2141 KiB

Open AccessReview

A Comprehensive View on the Impact of Chlorogenic Acids on Colorectal Cancer

by Andreea-Adriana Neamțu, Teodor Andrei Maghiar, Violeta Turcuș, Paula Bianca Maghiar, Anca-Maria Căpraru, Bianca-Andreea Lazar, Cristina-Adriana Dehelean, Ovidiu Laurean Pop, Carmen Neamțu, Bogdan Dan Totolici and Endre Mathe

Curr. Issues Mol. Biol. 2024, 46(7), 6783-6804; https://doi.org/10.3390/cimb46070405 - 2 Jul 2024

Viewed by 220

Abstract

Chlorogenic acids are plant secondary metabolites, chemically—polyphenols with similar biological activity, formed through the esterification of quinic acid and hydrocinnamic acid moieties. They are best known for their high concentration in coffee and other dietary sources and the antioxidant properties that they exhibit. Both chlorogenic acids and plant extracts containing significant amounts of the compounds show promising in vitro activity against colorectal cancer. With coffee being the most popular drink in the world, and colorectal cancer at an unfortunate peak in incidence and mortality, the mechanisms through which the anti-tumorigenic effect of chlorogenic acids could be functionalized for CRC prevention seem appealing to study. Therefore, this review aims to enable a better understanding of the modes of action of chlorogenic acids in combating carcinogenesis, with a focus on cell cycle arrest, the induction of apoptosis, and the modulation of Wnt, Pi3K/Akt, and MAPK signal transduction pathways, alongside the reduction in the number of inflammatory cytokines and chemokines and the counterintuitive beneficial elevation of oxidative stress. Full article

(This article belongs to the Special Issue Molecular Research in Bioactivity of Natural Products)

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13 pages, 3332 KiB

Open AccessArticle

Leonurine Exerts Anti-Inflammatory Effects in Lipopolysaccharide (LPS)-Induced Endometritis by Modulating Mouse JAK-STAT/PI3K-Akt/PPAR Signaling Pathways

by Yongbin Shao, Yan Luo, Yaoqiang Sun, Jingbo Jiang, Zhiyuan Li, Zhen Wang, Mengmeng Wang and Xinli Gu

Genes 2024, 15(7), 857; https://doi.org/10.3390/genes15070857 - 29 Jun 2024

Viewed by 197

Abstract

Endometritis is a common disease in postpartum cows, characterized by delayed uterine recovery due to endometrial inflammation. Although antibiotics and hormones are commonly used, they have certain limitations. One potential alternative is using motherwort extract, specifically leonurine, which exhibits anti-inflammatory properties. However, leonurine’s exact molecular mechanism of action remains unclear. In this study, 40 mice were randomly divided into four groups: a control group, endometritis model group, LPS + leonurine group (30 mg/kg), and LPS + dexamethasone group (5 mg/kg). Transcriptomic analysis revealed that leonurine modulates multiple signaling pathways, including JAK-STAT/PI3K-Akt, and influences the expression of key genes, such as Prlr, Socs2, Col1a1, and Akt1. Furthermore, leonurine effectively reduces levels of inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, and IL-1β (p < 0.01), which play a crucial role in regulating acute endometritis. Additionally, leonurine helps maintain cholesterol homeostasis and attenuates inflammation through the peroxisome proliferator-activated receptor (PPAR) signaling pathway by modulating genes such as Cyp27a1, Hmgcs1, and Scd2. These findings suggest that leonurine has a protective effect against LPS-induced endometritis and that its anti-inflammatory properties involve multiple pathways and targets, which are potentially mediated by regulating signaling pathways such as JAK-STAT/PI3K-Akt and PPAR. Full article

(This article belongs to the Section Molecular Genetics and Genomics)

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Abstract

In sub-Saharan Africa (SSA), the (sub)genotypes A1, D3, and E of the hepatitis B virus (HBV) prevail. Individuals infected with subgenotype A1 have a 4.5-fold increased risk of HCC compared to those infected with other (sub)genotypes. The effect of (sub)genotypes on protein expression and host signalling has not been studied. Mass spectrometry was used to analyse the proteome of Huh7 cells transfected with replication-competent clones. Proteomic analysis revealed significantly differentially expressed proteins between SSA (sub)genotypes. Different (sub)genotypes have the propensity to dysregulate specific host signalling pathways. Subgenotype A1 resulted in dysregulation within the Ras pathway. Ras-associated protein, RhoC, was significantly upregulated in cells transfected with subgenotype A1 compared to those transfected with other (sub)genotypes, on both a proteomic (>1.5-fold) and mRNA level (p < 0.05). Two of the main cellular signalling pathways involving RHOC, MAPK and PI3K/Akt/mTOR, regulate cell growth, motility, and survival. Downstream signalling products of these pathways have been shown to increase MMP2 and MMP9 expression. An extracellular MMP2 and MMP9 ELISA revealed a non-significant increase in MMP2 and MMP9 in the cells transfected with A1 compared to the other (sub)genotypes (p < 0.05). The upregulated Ras-associated proteins have been implicated as oncoproteins in various cancers and could contribute to the increased hepatocarcinogenic potential of A1. Full article

13 pages, 8213 KiB

Open AccessArticle

Transcriptome-Based Analysis of the Mechanism of Action of Metabolic Disorders Induced by Waterborne Copper Stress in Coilia nasus

by Dongyu Huang, Lu Zhang, Haifeng Mi, Tao Teng, Hualiang Liang and Mingchun Ren

Biology 2024, 13(7), 476; https://doi.org/10.3390/biology13070476 - 27 Jun 2024

Viewed by 237

Abstract

To reveal the effects of waterborne copper stress on gene expression changes, molecular pathways, and physiological functions in Coilia nasus, juvenile fish were equally divided into two experimental groups, and the copper levels were 1.61 ± 0.03 mg/L (copper-exposed group) and 0 mg/L (control group), respectively. After 4 h, gill tissue samples were collected for transcript sequencing analysis, and two libraries were constructed from the copper treatment group (Cu) and the control group (C) and sequenced using Illumina sequencing technology. The results showed that approximately 40.2–46.0 M clean reads were obtained from each library, and the percentage of uniquely mapped transcripts ranged from 80.57 to 84.93%. A total of 3915 differentially expressed genes (DEGs) were identified under waterborne copper stress, among which 1300 genes were up-regulated, and 2615 genes were down-regulated. Twelve DEGs were randomly selected for quantitative RT-PCR (qRT-PCR) analysis, and the results confirmed that the transcriptome analysis was reliable. Furthermore, the DEGs were subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, and the results showed that most of the DEGs were involved in metabolic pathways, including steroid biosynthesis, glutathione metabolism, and peroxisome proliferator-activated receptor (PPAR) signaling pathways. Furthermore, due to the waterborne copper levels, gsk-3β was significantly up-regulated, while other metabolism-related genes (tor, pi3k, lpl, aqp7, fabp3) were significantly down-regulated. In addition, the copper-exposed group significantly reduced the expression of some immunity genes (ifn-γ, stat1, cxcl10, and tgf-β), and enhanced the expression of il-1β and tnf-α. In summary, these results indicated that copper causes metabolic disorders and insufficient energy supply in the body, and induces oxidative stress, which results in reduced immune functions. Full article

(This article belongs to the Section Genetics and Genomics)

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