Molecular Biology Reports最新文献

Background: The treatment of metastatic castration-resistant prostate cancer (mCRPC) is still challenging clinically. Due to the refractor and highly metastatic phenotype of mCRPC, novel therapy strategies need to be investigated. Luteolin, a promising anticancer agent with various biological targets in many cancer types, also has a pro-oxidant effect that selectively triggers ROS and apoptosis. In recent years, among its ROS-mediated mechanisms, the inhibitory effect of luteolin on the nuclear factor-E2-related factor 2 (Nrf2), the main ROS scavenger protein in cancer cells, has been reported. However, no evidence exists that luteolin potentially regulates the Nrf2 or its regulator signaling pathway, Nrf2-Keap1-Cul3 axis, concerning its pro-oxidant effects associated with ROS-triggered apoptosis in any PCa cells or tumor model.

Methods and results: In the present study, we investigated for the first time whether the anticancer effect of luteolin is associated with pro-oxidant activity via the regulation of the Nrf2-Keap1-Cul3 redox signaling in PC3 and DU145 mCRPC cells. The results showed that luteolin significantly caused more cytotoxic, apoptotic, and pro-oxidant effects in a dose-dependent manner in mCRPC cells than in WPMY-1 normal prostate fibroblast cells for 72 h. Moreover, significant inhibition of Nrf2-Keap1-Cul3 redox signaling has occurred in response to increasing doses of luteolin in mCRPC cells.

Conclusions: The current study put forth the potential pro-oxidant inhibitory effect of luteolin on the Nrf2-Keap1-Cul3 axis in mCRPC cells for the first time. Thus, luteolin might be an attractive therapy strategy with an inhibitory effect on the cytoprotective Nrf2-Keap1-Cul3 redox signaling for treating mCRPC.

Background: Analysis of the content of the gut of fish helps in the understanding of their inter- and intra-specific interactions, fish behaviour, condition and energy intake. The stomach contents of the commercially important neritic tuna species of Sri Lanka, kawakawa (Euthynnus affinis), frigate tuna (Auxis thazard) and bullet tuna (Auxis rochei) were analysed to determine their feeding habits and to identify prey species.

Methods and results: The weighed stomachs of fish were dissected to reveal the types of prey found within. The prey was categorised into prey categories and each prey species was identified morphologically. Prey items which were partially digested were identified using DNA barcoding. The main prey category was small fish, followed by crustaceans and cephalopods. While the highest occurring prey category for E. affinis and A. rochei was fish, crustaceans dominated the A. thazard diet. DNA barcoding identified 11 prey items that were partially digested, which could not be identified to species-level morphologically. Of the prey items identified by DNA barcoding, four species of fish, three species of cephalopod and four species of crustaceans were identified. These prey item identifications confirmed that E. affinis, A. thazard and A. rochei are all nonspecific feeders.

Conclusions: This exhibits the value of molecular tools in the identification of species which have lost their distinguishable features due to digestion. Further, it illustrates the predator-prey relationships between these species, aiding in the management of prey and predator populations, ensuring that both populations remain stable, helping in the maintenance of the balance of the ecosystem.

Background: The progression of leukemia is substantially associated with the interactions of leukemic cells with surrounding cells within the bone marrow microenvironment (BMM), and these interactions were facilitated using exosomes as vital mediators. The current study aimed to examine the proliferative effects of exosomes derived from the HL-60 cell line, a representative of acute myeloblastic leukemia (AML), on the cell cycle progression of human bone marrow mesenchymal stromal cells (hBM-MSCs), a key element of the BMM.

Methods and results: hBM-MSCs were treated with different concentrations of AML-derived exosomes from the HL-60 cell line. The results were obtained from MTT, cell proliferation, cell cycle, and RT-qPCR evaluations. In the current study, we found that the proliferation effects of AML-derived exosomes relied on the dose and the time, and the optimal effects of exosomes were seen in 50 μg/ml, 48 h treatment. Flow cytometry analysis revealed a significant increase in the G1 phase, showing a 1.6-fold change compared to the control group (p value < 0.0001). RT-qPCR results demonstrated a significant upregulation of CCND1 (3.3-fold, p value < 0.0001), CDK4 (3.7-fold, p value < 0.0001), CDK6 (3.3-fold, p value < 0.0001), RAS (3.2-fold, p value < 0.0001), and Erk (3.4-fold, p value < 0.0001) expression levels, along with increased Ki-67 (2.6-fold, p value < 0.0001) levels. Moreover, treatment with 50 μg/ml, 48 h of AML-derived exosomes resulted in a notable reduction in BM-MSC apoptosis both in early (p value < 0.0001) and late (p value < 0.0001) apoptosis rate compared to control group.

Conclusions: The findings will be of interest to AML-derived exosomes, which were able to potentiate the activation of the signaling pathways involved in the survival and proliferation of hBM-MSCs. Our findings suggest their specific targeting as a potential therapeutic strategy against cancer progression and metastasis.

Fibromyalgia (FM) is a complex, chronic pain syndrome characterized by widespread musculoskeletal pain, fatigue, and cognitive disturbances. Despite its prevalence, the pathophysiology of FM remains poorly understood, with current treatments often providing limited relief. Recent studies have suggested that metformin, a widely used antidiabetic drug, may have potential therapeutic benefits for chronic pain conditions, including FM. This review aims to provide current insights into the role of metformin in FM pathophysiology, focusing on its neurotransmitter-modulating and anti-inflammatory effects. Metformin has been shown to mitigate neuroinflammation, protect neural tissues, and modulate key neurotransmitters involved in pain and mood regulation. These effects are particularly evident in animal models, where metformin has been observed to reduce pain sensitivity, improve mood-related behaviors, and decrease levels of pro-inflammatory cytokines like interleukin 1-beta (IL-1β). Additionally, the ability of metformin to influence serotonin, norepinephrine, and glutamate levels suggests a potential mechanism for its analgesic and mood-stabilizing effects. However, the current evidence is largely preclinical, and further research is needed to confirm these findings in human studies. This review aims to encourage researchers to explore the association between metformin and FM more deeply, with the hope of uncovering new therapeutic strategies that could offer relief to FM patients.

Background: Tomato (Solanum lycopersicum L.) is a widely cultivated crop in tropical regions, but its production is often hampered by significant losses attributed to diseases like tomato leaf curl virus (ToLCV), fusarium wilt and root-knot nematode.

Methods and results: This study employed an integrated approach utilizing both co-dominant and dominant SCAR markers, selected for specific resistance genes (ToLCV-Ty-1, Ty-2, Ty-2, Fusarium wilt (Race-2)-I-2, and Root-knot nematode-Mi-1. These markers with their specific gene of interest were used to screen the ten fresh market breeding lines of tomato. The P625 marker played a pivotal role in the identification process of Ty-3 alleles and effectively distinguishing between Ty-3a and Ty-3. I-2/5 (Fusarium wilt I-2), and Mi-23 (Root-knot nematode Mi-1) effectively identified and discriminated between heterozygous and homozygous states of specific genes. All resistant lines and a susceptible line for ToLCV (Ty-1, Ty-2, Ty-3), Fusarium wilt ((Race-2)- I-2) and Root-knot nematode underwent sequencing using specific primer pairs through the Sanger dideoxy technique. The resulting nucleotide sequences were aligned utilizing MEGA7 bioinformatic software and subjected to nucleotide BLAST in the NCBI database to determine sequence per cent identity and query cover, facilitating comparison with other submitted sequences.

Conclusion: The determination of genomic positions for these nucleotide sequences may enable researchers to cartographically pinpoint the locations of genetic variations within the genome.

Background: The genetic and epigenetic alterations observed in acute myeloid leukemia (AML) contribute to its heterogeneity, influencing disease progression response to therapy, and patient outcomes. The use of antisense oligonucleotides (ASOs) technology allows for the design of oligonucleotide inhibitors based on gene sequence information alone, enabling precise targeting of key molecular pathways or specific genes implicated in AML.

Methods and results: Midostaurin, a FLT3 specific inhibitor and ASOs targeting particular genes, exons, or mutations was conducted using AML models. This ASOs treatment was designed to bind to exon 7 of the MBNL1 (muscleblind-like) gene. Another target was the FLT3 gene, focusing on two aspects: (a) FLT3-ITD (internal tandem duplication), to inhibit the expression of this aberrant gene form, and (b) the FLT3 in general. Treated and untreated cells were analyzed using quantitative PCR (qPCR), dot blot, and Raman spectroscopy. This study contrasts midostaurin with ASOs that inhibit FLT3 protein production or its isoforms via mRNA degradation. A trend of increased FLT3 expression was observed in midostaurin-treated cells, while ASO-treated cells showed decreased expression, though these changes were not statistically significant.

Conclusions: In AML, exon 7 of MBNL1 is involved in several cellular processes and in this study, exon 7 of MBNL1 was targeted for method optimization, with the highest block of the exon 7 gene variant observed 48 h post-transfection. Midostaurin, a multitargeted kinase inhibitor, acts against the receptor tyrosine kinase FLT3, a critical molecule in AML pathogenesis. While midostaurin blocks FLT3 signaling pathways, it paradoxically increases FLT3 expression.

Background: The phytohormone salicylic acid (SA) serves as a crucial signaling molecule within the realm of plant immunity, playing an indispensable role in both local and systemic acquired resistance (SAR). N-hydroxypipecolic acid (NHP), a derivative of L-lysine, is integral to the induction of SAR. Recent investigations have illuminated the intricate manner in which NHP orchestrates the establishment of SAR in conjunction with the immune signal SA.

Methods and results: To further explore the mechanisms governing the synergistic regulation of SAR by SA and NHP, we conducted an extensive phosphoproteomic analysis aimed at identifying the phosphoproteins modulated either commonly or uniquely by SA and NHP, employing a phosphoproteomics platform built upon high-resolution mass spectrometry. Our study revealed a total of 133 phosphopeptides, derived from 115 distinct proteins, exhibiting exclusive responsiveness to NHP treatment. In contrast, 229 phosphopeptides sourced from 204 proteins demonstrated exclusive sensitivity to SA treatment. Additionally, the phosphorylation status of 215 proteins, including numerous kinases, phosphatases, transcription factors, and proteins implicated in membrane trafficking, was commonly modulated by both SA and NHP.

Conclusion: This investigation offers detailed insights into the key phosphoproteins influenced either collectively or specifically by SA and NHP, thereby enabling further exploration of the mechanisms underlying the synergistic regulation of immune responses orchestrated by these two potent molecules.

Nano bio-encapsulation of phyto-vaccines for cancer has marked a cutting-edge strategy that brings together nanotechnology with plant-derived vaccines to enhance cancer therapy. Phyto-vaccines, isolated from bioactive compounds found in plants called protein bodies, have been shown to potentially stimulate the immune system to recognise and destroy cancer cells. However, challenges such as poor stability, rapid degradation, and limited bioavailability in the body have hindered their clinical application. Nano bio-encapsulation offers a solution by packaging these phyto-vaccines into nanoscale carriers such as lectins have provided ways to overcome these limitations. They protect the protein bodies from degradation by proteolytic enzymes, enhance targeted delivery to cancer cells, and enable controlled release. This approach not only improves the bio-distribution and potency of the vaccines but also minimizes side effects, making it a highly promising, sustainable, and efficient method for cancer immunotherapy. As research progresses, this technology has the potential to revolutionize cancer treatment by providing safer and more precise therapeutic options. This review focuses on the concept of nano bio-encapsulation of phyto-vaccines for cancer treatment. It explores how nanotechnology can enhance the stability, bioavailability, and targeted delivery of plant-derived vaccines, addressing the limitations of traditional vaccines. The review delves into the potential of this innovative strategy to advance cancer immunotherapy, providing a comprehensive overview of current research and future directions.

Background: Frankliniella schultzei (Trybom) is a serious pest and a carrier of tospoviruses in major agricultural crops. This species is a historical and unresolved species complex that contains genetically different cryptic species across the globe.

Methods and results: DNA barcodes were generated from freshly collected specimens of F. schultzei from India and Australia using the sanger sequencing. Seventy-five COI sequences were generated from India and Australia. Moreover, 318 sequences were downloaded (India, Australia, Pakistan, and Africa) from the NCBI GenBank to explore the genetic diversity and phylogeny. The minimum and maximum mean interspecific distance between 393 sequences was found to be 7.97% and 21.50%, respectively. Bayesian and Neighbour joining clustering indicated the presence of five putative species within F. schultzei that had sympatry and allopatry. Moreover, 20 haplotypes and 140 polymorphic sites were identified. The African clade is unique; it does not share haplotypes with any other countries, suggesting it may represent the true F. schultzei. Haplotype network analysis showed shallow gene flow and deep genetic variation between the populations. Signatures of recent population history events were measured using Fu's Fs test and Tajima's D test. Morphometric analysis based on seven characters is also carried out.

Conclusion: Phylogeny and genetic distance revealed the presence of five putative species within F. schultzei. On the contrary, morphology does not unequivocally corroborate the phylogenetic results, as morphometric analysis showed overlap among these clades. To resolve F. schultzei species complex, whole genome-based sequencing data are very much necessitated.

From soil to plant, the water and ions, enter the root system through the symplast and apoplast pathways. The latter gains significance under salt stress and becomes a major port of entry of the dissolved salts particularly the sodium ions into the root vasculature. The casparian strip (CS), a lignified barrier circumambulating the root endodermal cells' radial and transverse walls regulates the movement of water and solutes in and out of the stele. The development of CS begins with the synthesis of a protein scaffold made of CASPARIAN STRIP MEMBRANE DOMAIN PROTEINs (CASPs), followed by lignin deposition involving the enzymatic machinery viz., ENHANCED SUBERIN 1 (ESB1), RESPIRATORY BURST OXIDASE HOMOLOG F (RBOHF), and PEROXIDASE 64 (PER64), etc. Towards maintaining the integrity of the CS, the CASPARIAN STRIP INTEGRITY FACTOR 1/2-SCHENGEN 3-SCHENGEN 1 (CIF1/2-SGN3-SGN1) signaling pathway has been found to play a significant role as a barrier surveillance system, the resultant is compensatory lignification of the radial and stele-facing transversal walls of endodermis. This leads to the formation of 'U' shaped lignified structures that enable an effective apoplastic barrier mechanism to prevent the influx of sodium ions into the stele. Rice, the major staple crop is generally classified as salt-susceptible, however, root cross-sectional anatomy of selected salt-tolerant genotypes exhibits an early and enhanced lignification of the endodermis. For instance, in the salt-tolerant landrace Mundan, the development of CS is accompanied by the formation of continuous 'U' shaped lignified structures along the endodermal walls under salt stress.