Mitogen-activated Protein Kinase Research Articles

Genome‑wide identification of circular RNAs and MAPKs reveals the regulatory networks in response to green peach aphid infestation in peach (Prunus persica)

The green peach aphid (GPA), Myzus persicae (Sulzer), is a serious agricultural pest with a worldwide distribution and a vector of over 100 plant viruses. Various pathways, such as the mitogen-activated protein kinase (MAPK) cascades, play pivotal roles in signaling plant defense against pest attack, and circular RNAs (circRNAs) regulate the expression of mRNAs in response to pest attack. However, the mechanism underlying peach (Prunus persica) response to GPA attack remains unclear. The present study initially identified and characterized 316 circRNAs and 18 PpMAPKs from healthy and GPA-infested peach leaves by whole-transcriptome sequencing and predicted the differentially expressed circRNAs (DECs) after GPA infestation. PCR and Sanger sequencing confirmed the presence of six DECs in peach samples. Besides, RNA sequencing analysis detected 13 DECs, including 5 upregulated and 8 downregulated ones, in peach in response to the GPA attack. Gene ontology (GO) enrichment analysis indicated that specific DECs play crucial roles in the MAPK signaling pathway, and qRT-PCR revealed that GPA infestation altered the expression patterns of PpMAPKs. Finally, five circRNAs, three microRNA (miRNAs), and two MAPK target genes were identified to interact as a network and perform critical roles in modulating the MAPK pathway in the peach during GPA infestation.

Helicase-assisted continuous editing for programmable mutagenesis of endogenous genomes.

Deciphering the context-specific relationship between sequence and function is a major challenge in genomics. Existing tools for inducing locus-specific hypermutation and evolution in the native genome context are limited. Here we present a programmable platform for long-range, locus-specific hypermutation called helicase-assisted continuous editing (HACE). HACE leverages CRISPR-Cas9 to target a processive helicase-deaminase fusion that incurs mutations across large (>1000-base pair) genomic intervals. We applied HACE to identify mutations in mitogen-activated protein kinase kinase 1 (MEK1) that confer kinase inhibitor resistance, to dissect the impact of individual variants in splicing factor 3B subunit 1 (SF3B1)-dependent missplicing, and to evaluate noncoding variants in a stimulation-dependent immune enhancer of CD69. HACE provides a powerful tool for investigating coding and noncoding variants, uncovering combinatorial sequence-to-function relationships, and evolving new biological functions.

Mycobacterium tuberculosis Suppresses Inflammatory Responses in Host through Its Cholesterol Metabolites.

Cholesterol is a key carbon source for Mycobacterium tuberculosis (Mtb) survival and persistence within macrophages. However, little is known about the role of cholesterol metabolism by Mtb in host-Mtb interplay. Here, we report the immune suppression mediated by Mtb's cholesterol metabolites. Conducting the cholesterol metabolic profiling and loss-of-function experiments, we show that the cholesterol oxidation products catalyzed by a thiolase FadA5 from Mtb H37Ra, 4-androstenedione (AD), and its derivant 1,4-androstenedione (ADD) inhibit the expression of pro-inflammatory cytokines and thus promote bacterial survival in bone marrow-derived macrophages (BMDMs). Our time-resolved fluorescence resonance energy transfer (TR-FRET)-based screening further identifies the nuclear receptor LXRα as the target of ADD. Activation of LXRα via ADD impedes the nuclear factor-κB (NF-κB) and mitogen-activated protein kinases (MAPK) signaling and reduces cholesterol accumulation in lipid rafts upon TLR4 simulation, thereby compromising the inflammatory responses. Our findings provide the evidence that Mtb could suppress the host immunity through its cholesterol metabolic enzyme and products, which are potential targets for screening novel anti-tuberculosis (TB) agents.

Mechanistic insights on the role of Nrf-2 signalling in Huntington's disease.

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder affecting individualsworldwide. It is characterized by progressive motor dysfunction, cognitive decline, and psychiatric disturbances.The pathogenesis of HD involves oxidative stress, neuroinflammation, and mitochondrial dysfunction.Nuclear factor erythroid 2-related factor 2 (Nrf2), a key transcription factor regulating cellular responses to redox imbalance and inflammation, has emerged as a potential target for therapeutic intervention. Through the use of a number of different search engines like Scopus, PubMed, Elsevier and Bentham, aliterature review was carried out with the keywords 'Huntington's Disease, 'Pathology of HD' and 'Nrf2 signallingpathway'.Using the keywords that were given above, this review was carried out in order to collect the most recent publications and gain an understanding of the breadth of the extensive research that has been conducted on the role of Nrf2 in HD pathogenesis. Oxidative stress and neuroinflammation significantly contribute to HD progression. Activation of Nrf2 offers neuroprotection by enhancing anti-oxidant defense mechanisms.Furthermore, several signaling pathways, play crucial roles in HD pathophysiology.Pharmacological modulation of these pathways through selective inhibitors or agonists shows promise for the development of new therapeutic strategies. The various downstream pathways such as extracellular signal-related kinase (ERK), phosphoinositide3-Kinase (PI3-K), 5'-AMP-activated protein kinase (AMPK), Sirtuins, Mitogen-activated protein kinases (MAPK) plays a role in alleviating pathophysiology of HD.Diverse reports of these studies demonstrated PI3-K/AMPK/ERK/Sirtuins activators and MAPK inhibitors as encouraging targets in alleviating HD pathophysiology.

CLAVATA3 INSENSITIVE RECEPTOR KINASEs regulate lateral root initiation and spacing in Arabidopsis.

The root system architecture is very critical for plants to adapt to ever-changing environmental stimulations and is largely affected by lateral roots (LRs). Therefore, how plants regulate LR initiation and spacing is a key point for root system development. Previous studies have shown that RECEPTOR-LIKE KINASE 7 (RLK7) and its ligand TARGET OF LBD SIXTEEN 2 (TOLS2) control the initiation and spacing of LRs. However, the molecular mechanism underlying the perception and transduction of the TOLS2 signal by RLK7 remains to be elucidated. In this study, we explored whether CLAVATA3 INSENSITIVE RECEPTOR KINASEs (CIKs) are critical signaling components during Arabidopsis (Arabidopsis thaliana) LR development by investigating phenotypes of cik mutants and examining interactions between CIKs and members of the RLK7-mediated signaling pathway. Our results showed that high-order cik mutants generated more LRs because of more LR initiation and defective LR spacing. The cik mutants showed reduced sensitivity to applied TOLS2 peptides. TOLS2 application enhanced the interactions between CIKs and RLK7 and the RLK7-dependent phosphorylation of CIKs. In addition, overexpression of transcription factor PUCHI and constitutive activation of MITOGEN-ACTIVATED PROTEIN KINASE KINASE 4 (MKK4) and MKK5 partially rescued the spacing defects of LRs in cik and rlk7-3 mutants. Moreover, we discovered that auxin maximum in pericycle cells altered subcellular localization of CIKs to determine lateral root founder cells. These findings revealed that CIKs and RLK7 function together to perceive the TOLS2 signal and regulate LR initiation and spacing through the MKK4/5-MPK3/6-PUCHI cascade.

Cellular and Molecular Mechanisms of Hypertrophy of Ligamentum Flavum.

Hypertrophy of the ligamentum flavum (HLF) is a common contributor to lumbar spinal stenosis (LSS). Fibrosis is a core pathological factor of HLF resulting in degenerative LSS and associated low back pain. Although progress has been made in HLF research, the specific molecular mechanisms that promote HLF remain to be defined. The molecular factors involved in the onset of HLF include increases in inflammatory cytokines such as transforming growth factor (TGF)-β, matrix metalloproteinases, and pro-fibrotic growth factors. In this review, we discuss the current understanding of the mechanisms involved in HLF with a particular emphasis on aging and mechanical stress. We also discuss in detail how several pathomechanisms such as fibrosis, proliferation and apoptosis, macrophage infiltration, and autophagy, in addition to several molecular pathways involving TGF-β1, mitogen-activated protein kinase (MAPKs), and nuclear factor-κB (NF-κB) signaling, PI3K/AKT signaling, Wnt signaling, micro-RNAs, extracellular matrix proteins, reactive oxygen species (ROS), etc. are involved in fibrosis leading to HLF. We also present a summary of the current advancements in preclinical animal models for HLF research. In addition, we update the current and potential therapeutic targets/agents against HLF. An improved understanding of the molecular processes behind HLF and a novel animal model are key to developing effective LSS prevention and treatment strategies.

Exploring the Phytochemistry, Signaling Pathways, and Mechanisms of Action of Tanacetum parthenium (L.) Sch.Bip.: A Comprehensive Literature Review.

The traditional use of Tanacetum parthenium (L.) Sch.Bip., commonly known as feverfew, extends across various medical conditions, notably those associated with pain and inflammation. In alignment with the growing trend towards developing medications that target specific signaling pathways for enhanced efficacy and reduced side effects, extensive research has been conducted to investigate and validate the pharmacological effects of feverfew. Among its bioactive compounds, parthenolide stands out as the most potent, categorized as a germacranolide-type sesquiterpene lactone, and has been extensively studied in multiple investigations. Significantly, the anti-inflammatory properties of feverfew have been primarily attributed to its capacity to inhibit nuclear factor-kappa B (NF-κB), resulting in a reduction in pro-inflammatory cytokines like tumor necrosis factor-alpha (TNF-α). Furthermore, the anticancer properties of feverfew have been associated with the modulation of Mitogen-Activated Protein Kinase (MAPK) and NF-κB signaling pathways. This study further delves into the neuroprotective potential of feverfew, specifically in the management of conditions such as migraine headaches, epilepsy, and neuropathic pain through various mechanisms. The core objective of this study is to elucidate the phytochemical composition of feverfew, with a particular emphasis on understanding the molecular mechanisms and examining the signaling pathways that contribute to its pharmacological and therapeutic effects. Additionally, the safety, toxicity, and potential adverse effects of feverfew are comprehensively evaluated, with an overarching goal of providing valuable insights into the plant's potential for targeted and effective treatments.

TRIM21 induces selective autophagic degradation of c-Myc and sensitizes regorafenib therapy in colorectal cancer

Kirsten rat sarcoma virus (KRAS) mutation is associated with malignant tumor transformation and drug resistance. However, the development of clinically effective targeted therapies for KRAS-mutant cancer has proven to be a formidable challenge. Here, we report that tripartite motif-containing protein 21 (TRIM21) functions as a target of extracellular signal-regulated kinase 2 (ERK2) in KRAS-mutant colorectal cancer (CRC), contributing to regorafenib therapy resistance. Mechanistically, TRIM21 directly interacts with and ubiquitinates v-myc avian myelocytomatosis viral oncogene homolog (c-Myc) at lysine 148 (K148) via K63-linkage, enabling c-Myc to be targeted to the autophagy machinery for degradation, ultimately resulting in the downregulation of enolase 2 expression and inhibition of glycolysis. However, mutant KRAS (KRAS/MT)-driven mitogen-activated protein kinase (MAPK) signaling leads to the phosphorylation of TRIM21 (p-TRIM21) at Threonine 396 (T396) by ERK2, disrupting the interaction between TRIM21 and c-Myc and thereby preventing c-Myc from targeting autophagy for degradation. This enhances glycolysis and contributes to regorafenib resistance. Clinically, high p-TRIM21 (T396) is associated with an unfavorable prognosis. Targeting TRIM21 to disrupt KRAS/MT-driven phosphorylation using the antidepressant vilazodone shows potential for enhancing the efficacy of regorafenib in treating KRAS-mutant CRC in preclinical models. These findings are instrumental for KRAS-mutant CRC treatment aiming at activating TRIM21-mediated selective autophagic degradation of c-Myc.

Comparative Efficacy of Current and Emerging Therapies for Cutaneous and Visceral Leishmaniasis: A Global Perspective

Leishmaniasis treatment has faced challenges with pentavalent antimonials, historically used but now showing resistance and high failure rates. The World Health Organization (WHO) recommended higher doses, but resistance in Nepal and misuse persist. Antimonials are no longer the preferred treatment for visceral leishmaniasis (VL) in the Indian subcontinent but are still used for cutaneous leishmaniasis (CL). Amphotericin B, especially liposomal amphotericin B (L-AmB), has become the preferred treatment for VL in the Indian subcontinent, with high efficacy and shorter treatment courses. Genetic insights into leishmaniasis reveal that parasite species and host immune responses are key factors in disease variation. Genetic analysis of atypical parasite isolates shows that genetic variations can lead to different disease patterns. Whole genome sequencing and proteomic analyses offer fresh insights into how parasite genes and proteins impact drug resistance, post-kala-azar dermal leishmaniasis (PKDL), and unusual disease presentations. Variations in hereditary unit copy numbers and single nucleotide polymorphisms contribute to genetic diversity and distinct tissue distribution, leading to distinct disease patterns. Genomic markers for drug resistance in Leishmania parasites include ATP-binding cassette (ABC) transporters, amino acid permease 3 (AAP3), and proteins like phosphoglycerate kinase (PGK) and mitogen-activated protein kinase (MAPK). These markers are associated with efflux of thiols and metals, antimony resistance, and protection against oxidative stress. Additionally, key proteins and enzymes in antioxidant defense mechanisms, such as iron superoxide dismutase-A (FeSOD-A), folate transporter 1 (FT1), and heat shock protein 83 (HSP83), play roles in drug resistance and parasite survival.

Combined MEK1/2 and ATR inhibition promotes myeloma cell death through a STAT3-dependent mechanism invitro and invivo.

Mechanisms underlying potentiation of the anti-myeloma (MM) activity of ataxia telangiectasia Rad3 (ATR) antagonists by MAPK (Mitogen-activated protein kinases)-related extracellular kinase 1/2 (MEK1/2) inhibitors were investigated. Co-administration of the ATR inhibitor (ATRi) BAY1895344 (BAY) and MEK1/2 inhibitors, for example, cobimetinib, synergistically increased cell death in diverse MM cell lines. Mechanistically, BAY and cobimetinib blocked STAT3 Tyr705 and Ser727 phosphorylation, respectively, and dual dephosphorylation triggered marked STAT3 inactivation and downregulation of STAT3 (Signal transducer and activator of transcription 3) downstream targets (c-Myc and BCL-XL). Similar events occurred in highly bortezomib-resistant (PS-R) cells, in the presence of patient-derived conditioned medium, and with alternative ATR (e.g. M1774) and MEK1/2 (trametinib) inhibitors. Notably, constitutively active STAT3 c-MYC or BCL-XL ectopic expression significantly protected cells from BAY/cobimetinib. In contrast, transfection of cells with a dominant-negative form of STAT3 (Y705F) sensitized cells to cobimetinib, as did ATR shRNA knockdown. Conversely, MEK1/2 knockdown markedly increased ATRi sensitivity. The BAY/cobimetinib regimen was also active against primary CD138+ MM cells, but not normal CD34+ cells. Finally, the ATR inhibitor/cobimetinib regimen significantly improved survival in MM xenografts, including bortezomib-resistant models, with minimal toxicity. Collectively, these findings suggest that combined ATR/MEK1/2 inhibition triggers dual STAT3 Tyr705 and Ser727 dephosphorylation, pronounced downregulation of cytoprotective targets and MM cell death, warranting attention as a novel therapeutic strategy in MM.

The syntaxin-binding protein STXBP5 regulates progerin expression.

Hutchinson-Gilfor progeria syndrome (HGPS) is caused by a mutation in Lamin A resulting in the production of a protein called progerin. The accumulation of progerin induces inflammation, cellular senescence and activation of the P53 pathway. In this study, through public dataset analysis, we identified Syntaxin Binding Protein 5 (STXBP5) as an influencing factor of progerin expression. STXBP5 overexpression accelerated the onset of senescence, while STXBP5 deletion suppressed progerin expression, delayed senility, and decreased the expression of senescence-related factors. STXBP5 and progerin have synergistic effects and a protein-protein interaction. Through bioinformatics analysis, we found that STXBP5 affects ageing-related signalling pathways such as the mitogen-activated protein kinase (MAPK) pathway, the hippo pathway and the interleukin 17 (IL17) signalling pathway in progerin-expressing cells. In addition, STXBP5 overexpression induced changes in transposable elements (TEs), such as the human endogenous retrovirus H internal coding sequence (HERVH-int) changes. Our protein coimmunoprecipitation (Co-IP) results indicated that STXBP5 bound directly to progerin. Therefore, decreasing STXBP5 expression is a potential new therapeutic strategy for treating ageing-related phenotypes in patients with HGPS.

Biochemical Defence of Plants against Parasitic Nematodes.

Plant parasitic nematodes (PPNs), such as Meloidogyne spp., Heterodera spp. and Pratylenchus spp., are obligate parasites on a wide range of crops, causing significant agricultural production losses worldwide. These PPNs mainly feed on and within roots, impairing both the below-ground and the above-ground parts, resulting in reduced plant performance. Plants have developed a multi-component defence mechanism against diverse pathogens, including PPNs. Several natural molecules, ranging from cell wall components to secondary metabolites, have been found to protect plants from PPN attack by conferring nematode-specific resistance. Recent advances in omics analytical tools have encouraged researchers to shed light on nematode detection and the biochemical defence mechanisms of plants during nematode infection. Here, we discuss the recent progress on revealing the nematode-associated molecular patterns (NAMPs) and their receptors in plants. The biochemical defence responses of plants, comprising cell wall reinforcement; reactive oxygen species burst; receptor-like cytoplasmic kinases; mitogen-activated protein kinases; antioxidant activities; phytohormone biosynthesis and signalling; transcription factor activation; and the production of anti-PPN phytochemicals are also described. Finally, we also examine the role of epigenetics in regulating the transcriptional response to nematode attack. Understanding the plant defence mechanism against PPN attack is of paramount importance in developing new, effective and sustainable control strategies.

Hyperthermia-mediated cell death via deregulation of extracellular signal-regulated kinase and c-Jun NH2-terminal kinase signaling

Hyperthermia is a promising anticancer treatment that induces heat stress, thereby stimulating various signal transduction pathways to maintain cellular homeostasis. Mitogen-activated protein kinases (MAPKs) associate various extracellular stimuli with cytoplasmic and nuclear mediators through a three-tiered cascade of kinases, including MAPKs, MAP2Ks, and MAP3Ks. In mammals, three major groups of MAPKs have been characterized: extracellular signal-regulated protein kinases (ERK1/2), p38 MAPKs (α, β, γ, and δ), and c-Jun NH2-terminal kinases (JNK1/2/3). Each group of MAPKs is activated by heat and exhibits distinct biological functions. Recent studies have indicated that in hyperthermia, MAPK signaling pathways regulate cell survival and death in unique ways. This review offers a concise overview of the MAPK signaling pathway, specifically ERK and JNK, focusing on their relevance in cancer, interplay with heat shock proteins or phosphatases, and current understanding of the MAPK signaling pathway in hyperthermia.

Conserved perception of host and non-host signals via the a-pheromone receptor Ste3 in Colletotrichum graminicola.

Understanding the interactions between fungal plant pathogens and host roots is crucial for developing effective disease management strategies. This study investigates the molecular mechanisms underpinning the chemotropic responses of the maize anthracnose fungus Colletotrichum graminicola to maize root exudates. Combining the generation of a deletion mutant with monitoring of disease symptom development and detailed analysis of chemotropic growth using a 3D-printed device, we identify the 7-transmembrane G-protein coupled receptor (GPCR) CgSte3 as a key player in sensing both plant-derived class III peroxidases and diterpenoids. Activation of CgSte3 initiates signaling through CgSo, a homolog to the Cell Wall Integrity Mitogen-Activated Protein Kinase (CWI MAPK) pathway scaffold protein identified in other filamentous fungi, facilitating the pathogen's growth towards plant defense molecules. The NADPH oxidase CgNox2 is crucial for peroxidase sensing but not for diterpenoid detection. These findings reveal that CgSte3 and CWI MAPK pathways are central to C. graminicola's ability to hijack plant defense signals, highlighting potential targets for controlling maize anthracnose.

TaCDPK1-5A positively regulates drought response through modulating osmotic stress responsive-associated processes in wheat (Triticum aestivum).

Wheat TaCDPK1-5A plays critical roles in mediating drought tolerance through regulating osmotic stress-associated physiological processes. Calcium (Ca2+) acts as an essential second messenger in plant signaling pathways and impacts plant abiotic stress responses. This study reported the function of TaCDPK1-5A, a calcium-dependent protein kinase (CDPK) gene in T. aestivum, in mediating drought tolerance. TaCDPK1-5A sensitively responded to drought and exogenous abscisic acid (ABA) signaling, displaying induced transcripts in plants under drought and ABA treatments. Yeast two-hybrid and co-immunoprecipitation assays revealed that TaCDPK1-5A interacts with the mitogen-activated protein kinase TaMAPK4-7D whereas the latter with ABF transcription factor TaABF1-3A, suggesting that TaCDPK1-5A constitutes a signaling module with above partners to transduce signals initiated by drought/ABA stressors. Overexpression of TaCDPK1-5A, TaMAPK4-7D and TaABF1-3A enhanced plant drought adaptation by modulating the osmotic stress-related physiological indices, including increased osmolyte contents, enlarged root morphology, and promoted stomata closure. Yeast one-hybrid assays indicated the binding ability of TaABF1-3A with promoters of TaP5CS1-1B, TaPIN3-5A, and TaSLAC1-3-2A, the genes encoding P5CS enzyme, PIN-FORMED protein, and slow anion channel, respectively. ChIP-PCR and transcriptional activation assays confirmed that TaABF1-3A regulates these genes at transcriptional level. Moreover, transgene analysis indicated that these stress-responsive genes positively regulated proline biosynthesis (TaP5CS1-1B), root morphology (TaPIN3-5A), and stomata closing (TaSLAC1-3-2A) upon drought signaling. Positive correlations were observed between yield and the transcripts of TaCDPK1-5A signaling partners in wheat cultivars under drought condition, with haplotype TaCDPK1-5A-Hap1 contributing to improved drought tolerance. Our study concluded that TaCDPK1-5A positively regulates drought adaptation and is a valuable target for molecular breeding the drought-tolerant cultivars in T. aestivum.

Mps1-Targeted Molecular Design of Melatonin for Broad-Spectrum Antifungal Agent Discovery.

Melatonin, a multifunctional class of natural products, has demonstrated antifungal activity, making it a promising candidate for developing antifungal agents. The mitogen-activated protein kinase (Mps1) within fungal pathogens has a target inhibitory effect of melatonin in fungi. We use a virtual screening strategy to design melatonin derivatives based on the melatonin-Mps1 targeting model. Of these, a multiflorane-substitution compound M-12 emerges as a potent antifungal agent, exhibiting broad-spectrum efficacy against eight phytopathogenic fungal species, and effectively reduces the severity of tomato gray mold, Fusarium head blight in wheat, Sclerotinia stem rot in rape, and peach brown rot. M-12 half-maximal effective concentration values (5.50 μM against Botrytis cinerea, 5.21 μM against Fusarium graminearum, 10.6 μM against Rhizoctonia solani, and 9.02 μM against Sclerotinia sclerotiorum) are better than those of commercial broad-spectrum fungicide azoxystrobin (55.0, 23.2, 46.5, and 17.7 μM, respectively). Antifungal activity of enantiomer (S)-M-12 (5.02 μM) is significantly greater than its (R)-enantiomer (23.6 μM) against B. cinerea. Molecular docking and transcriptome analysis reveal that M-12 achieves its antifungal effects by inhibiting Mps1 kinase, thereby suppressing fungal growth and virulence.

Schisandrin A Alleviates Inflammation and Oxidative Stress in Aβ25-35-Induced Alzheimer's Disease in Vitro Model.

Schisandra extract has therapeutic and preventive effects on Alzheimer's disease (AD). Therefore, this study evaluated the anti-AD potential of Schisandrin A (SCH A) using an in vitro cell model. SH-SY5Y and SK-N-SH cells were treated with 20 µM amyloid β-protein (Aβ)25-35. The Aβ25-35-induced cells were then exposed to different concentrations of SCH A (1, 5, 10, 15 µg/mL). Moreover, to further explore the role of the extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK) pathway in the anti-AD effects of SHC A, SH-SY5Y cells were treated with SCH A following incubation with ERK activator LM22B-10. The impact of SCH A on cell viability and apoptosis was evaluated using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and flow cytometry. Furthermore, the oxidative stress markers and inflammatory cytokine levels were also assessed. The reactive oxygen species (ROS) levels were examined using 2',7'-Dichlorodihydrofluorescein Diacetate (DCFH-DA) method. Finally, Western blot analysis was employed to evaluate the phospho-ERK1/2 (p-ERK1/2) and ERK1/2. We observed that SCH A treatment (5, 10, 15 µg/mL) substantially increased the cell viability (p < 0.05), and reduced the apoptosis rate (10 and 15 µg/mL) in SH-SY5Y and SK-N-SH cells (p < 0.05). SCH A significantly ameliorated oxidative stress and reduced inflammatory cytokine levels in Aβ25-35-induced cells (p < 0.05). Furthermore, SCH A up-regulated the p-ERK1/2 to ERK1/2 ratio in Aβ25-35-induced cells. However, LM22B-10 treatment was found to exacerbate this effect of SCH A (p < 0.05). SCH A reduces the Aβ25-35-induced inflammatory response and oxidative stress in SH-SY5Y and SK-N-SH cells, and the activation of the ERK/MAPK signaling pathway was related to its potential mechanism.

Butin Protects Keratinocytes From Particulate Matter 2.5 and Ultraviolet B-Mediated Damages.

Butin is a naturally occurring compound with a wide range of medicinal properties, including anti-inflammatory, anti-arthritic, and antioxidant properties. Particulate matter 2.5 (PM2.5) and ultraviolet B (UVB) radiation contribute to skin cell damage via the induction of oxidative stress. This study sought to assess the protective effects of butin against damage triggered by PM2.5 and UVB in human HaCaT keratinocytes. Assessments were performed to evaluate cell viability, apoptosis, and cellular component damage. Butin exhibited its protective ability via the inhibition of PM2.5-induced reactive oxygen species generation, lipid peroxidation, DNA damage, protein carbonylation, and mitochondrial damage. Butin reduced the PM2.5-induced c-Fos and phospho-c-Jun protein levels as well as mitogen-activated protein kinase. Furthermore, butin mitigated PM2.5- and UVB-induced apoptosis. Butin had the potential as a pharmaceutical candidate for treating skin damage caused by PM2.5 and UVB exposure.

Marine Staurosporine Analogues: Activity and Target Identification in Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer with high mortality and drug resistance and no targeted drug available at present. Compound 4, a staurosporine alkaloid derived from Streptomyces sp. NBU3142 in a marine sponge, exhibits potent anti-TNBC activity. This research investigated its impact on MDA-MB-231 cells and their drug-resistant variants. The findings highlighted that compound 4 inhibits breast cancer cell migration, induces apoptosis, arrests the cell cycle, and promotes cellular senescence in both regular and paclitaxel-resistant MDA-MB-231 cells. Additionally, this study identified mitogen-activated protein kinase kinase kinase 11 (MAP3K11) as a target of compound 4, implicating its role in breast tumorigenesis by affecting cell proliferation, migration, and cell cycle progression.

Identification of growth-related genes based on BSA in Pacific white shrimp Litopenaeus vannamei

The development of SNP genotyping techniques has facilitated the application of genome-wide association studies (GWAS) and genomic selection (GS) in plants and animals. However, the cost of high-throughput SNP genotyping is particularly high in the case of aquaculture animals which can produce a large number of offspring. Consequently, a cost effective method for trait-associated SNP identification and application was urgently needed in aquaculture breeding. In this study, a Bulk Segregation Analysis sequencing (BSA-seq) method was employed to identify growth-related single nucleotide polymorphisms (SNPs) and genes in the Pacific white shrimp Litopenaeus vannamei. Two independent families were used for this analysis to reduce the false positive. The DNA of individuals with the highest and lowest body weights was pooled separately. Two methods including the ED (Euclidean distance) method and the chi-square test were applied to calculate the allele differences between high and low growth rate individuals. A total of 24,325,437 SNPs were identified and consequently 1,299 SNPs and 163 genes were identified to be associated with growth traits. KEGG enrichment analysis showed that these genes were significantly enriched in phosphatidylinositol signaling system and phospholipase D signaling pathway. The diacylglycerol kinase genes, phosphatidylinositol 3-kinase genes, inositol polyphosphate 5-phosphatase genes, mitogen-activated protein kinase genes, myotubularin-related protein genes and epidermal growth factor receptor genes in these pathways were considered as candidate growth genes. This study demonstrated that the BSA-seq based on whole genome resequencing is cost-effective and useful in aquaculture. The results not only provide useful information for understanding the genetic basis of growth traits, but also offer a source of SNPs for marker-assisted selection (MAS) and genomic selection (GS) in shrimp.