Expression Of Relevant Genes Research Articles

Cataloging the Genetic Response: Unveiling Drought-Responsive Gene Expression in Oil Tea Camellia (Camellia oleifera Abel.) through Transcriptomics.

Drought stress is a critical environmental factor that significantly impacts plant growth and productivity. However, the transcriptome analysis of differentially expressed genes in response to drought stress in Camellia oleifera Abel. is still unclear. This study analyzed the transcriptome sequencing data of C. oleifera under drought treatments. A total of 20,674 differentially expressed genes (DEGs) were identified under drought stress, with the number of DEGs increasing with the duration of drought. Specifically, 11,793 and 18,046 DEGs were detected after 8 and 15 days of drought treatment, respectively, including numerous upregulated and downregulated genes. Gene Ontology (GO) enrichment analysis showed that the DEGs were primarily involved in various biological processes. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed that carbon metabolism, glyoxylate and dicarboxylate metabolism, proteasome, glycine, serine, and threonine metabolism were the main affected pathways. Among the DEGs, 376 protein kinases, 42 proteases, 168 transcription factor (TF) genes, and 152 other potential functional genes were identified, which may play significant roles in the drought response of C. oleifera. The expression of relevant functional genes was further validated using quantitative real-time PCR (qRT-PCR). These findings contribute to the comprehension of drought tolerance mechanisms in C. oleifera and bolster the identification of drought-resistant genes for molecular breeding purposes.

Long Noncoding RNA NKX2-1-AS1 Accelerates Non-Small Cell Lung Cancer Progression through the miR-589-5p/NME1 Axis.

Non-small cell lung cancer (NSCLC) is the most common malignancy worldwide, with a high death rate. Long noncoding RNA (LncRNA) NKX2-1 antisense RNA 1 (NKX2-1-AS1) has been reported to be an oncogene in lung tumorigenesis. However, the precise mechanism of NKX2-1-AS1 underlying NSCLC progression is blurry. The intention of our research was to probe the potential mechanism of NKX2-1-AS1 underlying NSCLC. NKX2-1-AS1 expression and relevant downstream gene expression were measured using RT-qPCR. Cell proliferation and apoptosis were determined by MTT assay, EdU assay along with flow cytometry analysis. Cell migratory and invasive abilities were inspected by transwell assay. Western blot and immunofluorescence staining were utilized to assess the levels of epithelial-mesenchymal transition (EMT)-related proteins. RNA pull-down together with luciferase reporter assays were performed to verify the interaction between NKX2-1-AS1 and its downstream RNAs. Xenograft tumor-bearing mouse models were built to analyze tumor growth in vivo. The results suggested that NKX2-1-AS1 was upregulated in NSCLC patient tissues and cell lines. NKX2-1-AS1 deficiency suppressed cell proliferation, migration, invasion and EMT while elevated apoptosis. NKX2-1-AS1 bound to miR-589-5p, and NME/NM23 nucleoside diphosphate kinase 1 (NME1) was targeted by miR-589-5p in NSCLC cells. Additionally, NKX2-1-AS1 accelerated the progression of NSCLC by regulating miR-589-5p/NME1 axis. NKX2-1-AS1 knockdown repressed tumor growth in vivo. In conclusion, NKX2-1-AS1 accelerated the NSCLC progression through interacting with miR-589-5p for NME1 upregulation, which may provide clues for NSCLC targeting therapy.

Development of a highly sensitive platform for protein–protein interaction detection and regulation of T cell function

We developed a highly sensitive assay for detecting protein-protein interaction using chimeric receptors comprising two molecules of interest in the extracellular domain and interferon alpha and beta receptor subunit 1 or 2 (IFNAR1/2) in the intracellular domain. This intracellular IFNAR1/2 reconstitution system (IFNARRS) proved markedly more sensitive than the NanoBiT system, currently considered one of the best detection systems for protein interaction. Employing chimeric receptors with extracellular domains from the IFNγ or IL-2 receptor and the intracellular domains of IFNAR1/2, the IFNARRS system effectively identifies low IFNγ or IL-2 levels. Cells stably expressing these chimeric receptors responded to IFNγ secreted by activated T cells following various stimuli, including a specific peptide-antigen. The activation signals were further enhanced by the expression of relevant genes, such as costimulators, via IFN-stimulated response elements in the promoters. Besides IFNγ or IL-2, the IFNARRS system demonstrated the capability to detect other cytokines by using the corresponding extracellular domains from these target cytokine receptors.

Effect of electrical muscle stimulation on the improvement of deltoid muscle atrophy in a rat shoulder immobilization model.

Immobilization following trauma or surgery induces skeletal muscle atrophy, and improvement in the muscle atrophy is critical for successful clinical outcomes. The purpose of this study is to evaluate the effect of electrical muscle stimulation (EMS) on muscle atrophy. The study design is a controlled laboratory study. Eighty rats (56 to establish the deltoid muscle atrophy [DMA] model and 24 to evaluate the effect of EMS on the model) were used. DMA was induced by completely immobilizing the right shoulder of each rat by placing sutures between the scapula and humeral shaft, with the left shoulder as a control. After establishing the DMA model, rats were randomly assigned into three groups: low-frequency EMS (L-EMS, 10 Hz frequency), medium-frequency EMS (M-EMS, 50 Hz frequency), and control (eight rats per group). After 3 weeks, the deltoid muscles of each rat were harvested, alterations in gene expression and muscle cell size were evaluated, and immunohistochemical analysis was performed. DMA was most prominent 3 weeks after shoulder immobilization. Murf1 and Atrogin were significantly induced at the initial phase and gradually decreased at approximately 3 weeks; however, MyoD expressed an inverse relationship with Murf1 and Atrogin. IL6 expression was prominent at 1 week. The time point for the EMS effect evaluation was selected at 3 weeks, when the DMA was the most prominent with a change in relevant gene expression. The M-EMS group cell size was significantly larger than that of L-EMS and control group in both the immobilized and intact shoulders (all p < 0.05), without significant differences between the L-EMS and control groups. The M-EMS group showed significantly lower mRNA expressions of Murf1 and Atrogin and higher expressions of MyoD and Col1A1 than that of the control group (all p < 0.05). In immunohistochemical analysis, similar results were observed with lower Atrogin staining and higher MyoD and Col1A1 staining in the M-EMS group. DMA model was established by complete shoulder immobilization, with the most prominent muscle atrophy observed at 3 weeks. M-EMS improved DMA with changes in the expression of relevant genes. M-EMS might be a solution for strengthening atrophied skeletal muscles and facilitating rehabilitation after trauma or surgery.

Modulation of naïve mesenchymal stromal cells by extracellular vesicles derived from insulin-producing cells: an in vitro study

This study was to determine whether extracellular vesicles (EVs) derived from insulin-producing cells (IPCs) can modulate naïve mesenchymal stromal cells (MSCs) to become insulin-secreting. MSCs were isolated from human adipose tissue. The cells were then differentiated to generate IPCs by achemical-based induction protocol. EVs were retrieved from the conditioned media of undifferentiated (naïve) MSCs (uneducated EVs) and from that of MSC-derived IPCs (educated EVs) by sequential ultracentrifugation. The obtained EVs were co-cultured with naïve MSCs.The cocultured cells were evaluated by immunofluorescence, flow cytometry, C-peptide nanogold silver-enhanced immunostaining, relative gene expression and their response to a glucose challenge.Immunostaining for naïve MSCs cocultured with educated EVs was positive for insulin, C-peptide, and GAD65. By flow cytometry, the median percentages of insulin-andC-peptide-positive cells were 16.1% and 14.2% respectively. C-peptide nanogoldimmunostaining providedevidence for the intrinsic synthesis of C-peptide. These cells released increasing amounts of insulin and C-peptide in response to increasing glucose concentrations. Gene expression of relevant pancreatic endocrine genes, except for insulin, was modest. In contrast, the results of naïve MSCs co-cultured with uneducated exosomes were negative for insulin, C-peptide, and GAD65. These findings suggest that this approach may overcome the limitations of cell therapy.

Linc01116 Silencing Inhibits the Proliferation and Invasion, Promotes Apoptosis of Chordoma Cells via Regulating the Expression of Mir-9-5p/PKG1.

Long intergenic non-protein coding RNA 1116 (LINC01116) plays a carcinogenic role in a variety of cancers. The study aims to investigate the roles of LINC01116 and hsa-miR-9-5p (miR-9-5p) and fathom their interaction in chordoma. The predicted binding sites between miR-9-5p with LINC01116 and phosphoglycerate kinase 1 (PGK1) by starBase were confirmed through dual-luciferase reporter assay. The behaviors of chordoma cells undergoing transfection with siLINC01116 or miR-9-5p inhibitor were determined by Cell Counting Kit-8 (CCK-8), colony formation, Transwell, and flow cytometry assays. The glucose consumption, lactate production, and adenosine triphosphate (ATP) production of chordoma cells were examined with specific kits. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were performed to determine relevant gene expressions in chordoma cells. Silencing of LINC01116 facilitated the apoptosis and expressions of Bcl-2- associated X (Bax), cleaved caspase-3 (C caspase-3) and miR-9-5p while repressing the cell cycle, viability, proliferation, invasion, glucose consumption, lactate production, ATP production, and expressions of PGK1 and Bcl-2. Meanwhile, LINC01116 sponged miR-9-5p, which could target PGK1. Moreover, the miR-9-5p inhibitor acted contrarily and reversed the role of siLINC01116 in chordoma cells. Besides, LINC01116 downregulation facilitated apoptosis and attenuated the proliferation and invasion of chordoma cells as well as PGK1 expression by upregulating miR-9-5p expression. LINC01116/miR-9-5p plays a regulatory role in the progression of chordoma cells and is a potential biomarker for chordoma.

Effects of gestational hypothyroidism on mouse brain development: Gabaergic systems and oxidative stress

Hormonal imbalance during pregnancy is a risk factor for neuropsychiatric impairment in the offspring. It has been suggested that hypothyroidism leads to dysfunction of cortical GABAergic interneurons and inhibitory system development that in turn underlies impairment of the central nervous system. Here we investigated how gestational hypothyroidism affected offspring GABAergic system development as well as redox regulation parameters, because of previous links identified between the two. Experimental Gestational Hypothyroidism (EGH) was induced in CD-1 mice with 0.02% methimazole (MMI) in drinking water from embryonic day 9 (E9) until tissue collection at embryonic day 14 (E14) or E18. We examined GABAergic cell distribution and inhibitory system development gene expression as well as redox relevant gene expression and direct measures across all embryos regardless of sex. Intrauterine restriction of maternal thyroid hormones significantly impacted both of these outcomes in brain, as well as altering redox regulation in the placenta. GAD67+ neuronal migration was reduced, accompanied by a disruption in gene expression influencing GABAergic cell migration and cortical inhibitory neural system development. EGH also altered embryonic brain gene expression of Gpx1, Nfe2l2, Cat levels in the dorsal E14 brains. Additionally, EGH resulted in elevated TBARS, Gpx1 and Nfe2l2 in the ventral E18 brains. Furthermore, EGH downregulated placental Gpx1 gene expression at E14 and increased protein oxidation at E18. These findings support the hypothesis that sufficient maternal thyroid hormone supply to the fetus influences central nervous system development, including processes of GABAergic system development and redox equilibrium.

Multiple Exposures to Sevoflurane General Anesthesia During Pregnancy Inhibit CaMKII/CREB Axis by Downregulating HCN2 to Induce an Autism-Like Phenotype in Offspring Mice.

The objective of this investigation was to examine the impact of multiple exposures to general anesthesia (GA) with sevoflurane on the offspring of pregnant mice, as well as to elucidate the underlying mechanism. Neurodevelopmental assessments, including various reflexes and behavioral tests, were conducted on the offspring in the GA group to evaluate neuronal cell development. Furthermore, neonatal mouse neuronal cells were isolated and transfected with a high-expression CREB vector (pcDNA3.1-CREB), followed by treatment with sevoflurane (0.72mol/L), ZD7288 (50μmol/L), and KN-62 (10μmol/L), or a combination of these compounds. The expression of relevant genes was then analyzed using qRT-PCR and western blot techniques. In comparison to the sham group, neonatal mice in the GA group exhibited significantly prolonged latencies in surface righting reflex, geotaxis test, and air righting reflex. Furthermore, there was a notable deceleration in the development of body weight and tail in the GA group. These mice also displayed impairments in social ability, reduced reciprocal social interaction behaviors, diminished learning capacity, and heightened levels of anxious behaviors. Additionally, synaptic trigger malfunction was observed, along with decreased production of c-Fos and neurotrophic factors. Sevoflurane was found to notably decrease cellular c-Fos and neurotrophic factor production, as well as the expression of HCN2 and CaMKII/CREB-related proteins. The inhibitory effects of sevoflurane on HCN2 or CaMKII channels were similar to those observed with ZD7288 or KN-62 inhibition. However, overexpression of CREB mitigated the impact of sevoflurane on neuronal cells. Repetitive exposure to sevoflurane general anesthesia while pregnant suppresses the CaMKII/CREB pathway, leading to the development of autism-like characteristics in offspring mice through the reduction of HCN2 expression.

DNA methylation profiles of cancer-related fatigue associated with markers of inflammation and immunometabolism.

Cancer patients are commonly affected by fatigue. Herein, we sought to examine epigenetic modifications (i.e., DNA methylation) related to fatigue in peripheral blood among patients during and after treatment for head and neck cancer (HNC). Further, we determined whether these modifications were associated with gene expression and inflammatory protein markers, which we have previously linked to fatigue in HNC. This prospective, longitudinal study enrolled eligible patients with data collected at pre-radiotherapy, end of radiotherapy, and six months and one-year post-radiotherapy. Fatigue data were reported by patients using the Multidimensional Fatigue Inventory (MFI)-20. DNA methylation (Illumina MethylationEPIC) and gene expression (Applied Biosystems Clariom S) arrays and assays for seven inflammatory markers (R&D Systems multiplex) were performed. Mixed models and enrichment analyses were applied to establish the associations. A total of 386 methylation loci were associated with fatigue among 145 patients (False Discovery Rate [FDR] < 0.05). Enrichment analyses showed the involvement of genes related to immune and inflammatory responses, insulin and lipid metabolism, neuropsychological disorders, and tumors. We further identified 16 methylation-gene expression pairs (FDR < 0.05), which were linked to immune and inflammatory responses and lipid metabolism. Ninety-one percent (351) of the 386 methylation loci were also significantly associated with inflammatory markers (e.g., interleukin 6, c-reactive protein; FDR < 0.05), which further mediated the association between methylation and fatigue (FDR < 0.05). These data suggest that epigenetic modifications associated with inflammation and immunometabolism, in conjunction with relevant gene expression and protein markers, are potential targets for treating fatigue in HNC patients. The findings also merit future prospective studies in other cancer populations as well as interventional investigations.

MyC Factor Analogue CO5 Promotes the Growth of Lotus japonicus and Enhances Stress Resistance by Activating the Expression of Relevant Genes.

The symbiotic relationship between arbuscular mycorrhizal fungi (AMF) and plants is well known for its benefits in enhancing plant growth and stress resistance. Research on whether key components of the AMF colonization process, such as MyC factors, can be directly utilized to activate plant symbiotic pathways and key functional gene expression is still lacking. In this paper, we found that, using a hydroponics system with Lotus japonicus, MyC factor analogue chitin oligomer 5 (CO5) had a more pronounced growth-promoting effect compared to symbiosis with AMF at the optimal concentration. Additionally, CO5 significantly enhanced the resistance of Lotus japonicus to various environmental stresses. The addition of CO5 activated symbiosis, nutrient absorption, and stress-related signaling pathways, like AMF symbiosis, and CO5 also activated a higher and more extensive gene expression profile compared to AMF colonization. Overall, the study demonstrated that the addition of MyC factor analogue CO5, by activating relevant pathways, had a superior effect on promoting plant growth and enhancing stress resistance compared to colonization by AMF. These findings suggest that utilizing MyC factor analogues like CO5 could be a promising alternative to traditional AMF colonization methods in enhancing plant growth and stress tolerance in agriculture.

Comprehensive bioinformatics analysis of integrator complex subunits: expression patterns, immune infiltration, and prognostic signature, validated through experimental approaches in hepatocellular carcinoma

BackgroundHepatocellular carcinoma (HCC) is a common gastrointestinal malignancy with a high incidence and poor prognosis. The subunits of the integrator complex (INTS1-14) play a crucial role in regulating genes dependent on RNA Polymerase II, which may be associated with cancer. However, the role of INTSs in HCC remains unclear. This study aims to comprehensively analyze the clinical value and potential role of INTS family genes in HCC through systematic bioinformatics analysis.MethodsWe employed various public databases, including UALCAN, HPA, Kaplan–Meier Plotter, GEPIA2, TNMplot, STRING, TIMER, and TISIDB, to investigate the expression levels, clinicopathological correlations, diagnostic and prognostic value, genetic alterations, co-expression network, molecular targets, and immune infiltration of INTSs in HCC. Additionally, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were utilized to investigate the biological functions of genes associated with INTSs. Furthermore, Western blot, real-time fluorescence quantitative reverse transcription polymerase chain reaction (RT-qPCR), and immunohistochemistry techniques were employed to assess the expression of relevant proteins and genes. The proliferation of HCC cells was evaluated using the CCK8 assay.ResultsWe found that in HCC, there was a significant upregulation of INTSs at the transcriptional level, particularly INTS1, INTS4, INTS7, and INTS8. Additionally, the protein levels of INTS1 and INTS8 were notably elevated. The overexpression of these INTSs was strongly correlated with tumor stages in HCC patients. INTS1, INTS4, INTS7, and INTS8 exhibited significant diagnostic and prognostic value in HCC. Moreover, their expression was associated with immune infiltrations and activated status, including B cells, CD8 + T cells, CD4 + T cells, NK cells, macrophages, and dendritic cells. Functional predictions indicated that INTS1, INTS4, INTS7, and INTS8 were involved in various cancer-related signaling pathways, such as TRAIL, IFN-gamma, mTOR, CDC42, Apoptosis, and the p53 pathway. Furthermore, we observed a significant upregulation of INTS1, INTS4, INTS7, and INTS8 expression in HCC cell lines compared to normal liver cell lines. The level of INTS1 protein was higher in cancerous tissues compared to adjacent non-cancerous tissues (n = 16), and the suppression of INTS1 resulted in a significant decrease in the proliferation of Huh7 cells.ConclusionThese findings indicate the potential of INTS family genes as diagnostic biomarkers and therapeutic targets in HCC. Further research is needed to understand the underlying mechanisms and explore clinical applications.

Computational identification of novel potential genetic pathogenesis and otherwise biomarkers in acute liver allograft rejection

Acute cellular rejection (ACR) is a prevalent postoperative complication following liver transplantation (LT), exhibiting an increasing incidence of morbidity and mortality. However, the molecular mechanisms of ACR following LT remain unclear. To explore the genetic pathogenesis and identify biomarkers of ACR following LT, three relevant Gene Expression Omnibus (GEO) datasets consisting of data on ACR or non-ACR patients after LT were comprehensively investigated by computational analysis. A total of 349 upregulated and 260 downregulated differentially expressed genes (DEGs) and eight hub genes (ISG15, HELZ2, HNRNPK, TIAL1, SKIV2L2, PABPC1, SIRT1, and PPARA) were identified. Notably, HNRNPK, TIAL1, and PABPC1 exhibited the highest predictive potential for ACR with AUCs of 0.706, 0.798, and 0.801, respectively. KEGG analysis of hub genes revealed that ACR following LT was predominately associated with ferroptosis, protein processing in the endoplasmic reticulum, complement and coagulation pathways, and RIG-I/NOD/Toll-like receptor signaling pathway. According to the immune cell infiltration analysis, γδT cells, NK cells, Tregs, and M1/M2-like macrophages had the highest levels of infiltration. Compared to SIRT1, ISG15 was positively correlated with γδT cells and M1-like macrophages but negatively correlated with NK cells, CD4+ memory T cells, and Tregs. In conclusion, this study identified eight hub genes and their potential pathways, as well as the immune cells involved in ACR following LT with the greatest levels of infiltration. These findings provide a new direction for future research on the underlying mechanism of ACR following LT.

Elucidating the role of rice straw biochar in modulating Helianthus annuus L. antioxidants, secondary metabolites and soil post-harvest characteristics in different types of microplastics

The emergence of microplastics (MPs) as pollutants in agricultural soils is increasingly alarming, presenting significant threats to soil ecosystems. Given the widespread contamination of ecosystems by various types of MPs, including polystyrene (PS), polyvinyl chloride (PVC), and polyethylene (PE), it is crucial to understand their effects on agricultural productivity. The present study was conducted to investigate the effects of different types of MPs (PS, PVC, and PE) on various aspects of sunflower (Helianthus annuus L.) growth with the addition of rice straw biochar (RSB). This study aimed to examine plant growth and biomass, photosynthetic pigments and gas exchange characteristics, oxidative stress indicators, and the response of various antioxidants (enzymatic and non-enzymatic) and their specific gene expression, proline metabolism, the AsA–GSH cycle, cellular fractionation in the plants and post-harvest soil properties. The research outcomes indicated that elevated levels of different types of MPs in the soil notably reduced plant growth and biomass, photosynthetic pigments, and gas exchange attributes. Different types of MPs also induced oxidative stress, which caused an increase in various enzymatic and non-enzymatic antioxidant compounds, gene expression and sugar content; notably, a significant increase in proline metabolism, AsA–GSH cycle, and pigmentation of cellular components was also observed. Favorably, the addition of RSB significantly increased plant growth and biomass, gas exchange characteristics, enzymatic and non-enzymatic compounds, and relevant gene expression while decreasing oxidative stress. In addition, RSB amendment decreased proline metabolism and AsA-GSH cycle in H. annuus plants, thereby enhancing cellular fractionation and improving post-harvest soil properties. These results open new avenues for sustainable agriculture practices and show great potential for resolving the urgent issues caused by microplastic contamination in agricultural soils.

A bi-adjuvant nanovaccine amplifying STING activation for cancer immunotherapy

The insufficient immune activation and immunosuppressive microenvironment restrict the therapeutic efficacy of cancer vaccines. Herein, we exploited a bi-adjuvant nanovaccine to amplify the activation of the stimulator of interferon genes (STING) for potent and durable anti-tumor immunity. STING agonist (MnO2 nanoparticles), toll-like receptor 9 agonist (CpG), and antigenic proteins or peptides were strategically formulated into nanovaccines (MnC NVs) by a one-step biomineralization method. The nanovaccine efficiently targeted dendritic cells of draining lymph nodes, in which CpG-mediated the stimulation of nuclear factor-kappa B pathway augmented STING signaling. RNA sequencing analysis validated the enhanced expression of relevant genes of type-I interferon signaling pathways. The priming of antigen-specific CD8+ T cells and humoral immune responses led to potent tumor growth inhibition and prolonged survival time in melanoma and human papilloma virus-derived tumor models. MnC NVs were able to synergize with immune checkpoint blockade therapy, with 80 % survival over 40 days in TC-1 tumor model. Moreover, rechallenging of tumor-free mice with homotypic cells resulted in complete tumor growth inhibition, suggesting the generation of a long-term memory effect. The simplified nanovaccine platform provides a safe and robust strategy to boost STING-mediated anti-tumor immunity for personalized cancer immunotherapy, showing significant potential for clinical translation.

Application of therapeutic nucleic acids and RNA interference to create products for personalised medicine

INTRODUCTION. Small interfering RNAs (siRNAs) are among the most promising types of therapeutic nucleic acids aiming at the inhibition of pathogenetically relevant gene expression through the RNA interference mechanism. However, the limited bioavailability and immunogenicity of siRNAs and imperfect delivery systems hinder the clinical potential and applicability of siRNA medicinal products.AIM. This study aimed to summarise recent advances in the development of siRNA medicinal products and the corresponding delivery systems, review clinical trial results, and outline future development prospects for these medicinal products.DISCUSSION. This article covers the molecular mechanisms underlying RNA interference, the considerations for siRNA development, and the techniques for effective siRNA delivery. The article dwells upon various systems for nucleic acid delivery to targeted cells. The most promising delivery systems are non-viral systems, including liposomes, exosomes, nanoparticles, polymers, cell-penetrating peptides, and GalNAc ligands. Their main advantages include their ease of complexation with nucleic acids, modification and functionalization potential, favourable safety profile, ability to cross biological barriers, and tropism to target tissues. The article summarises the information that has accumulated over the past few years in clinical trials of siRNA medicinal products for a range of conditions, including metabolic disorders, infections, and cancers, as well as hereditary, ophthalmic, renal, and hepatic diseases. Special attention is paid to siRNA medicinal products undergoing clinical trials (over 10 products) and approved for clinical use (6 products, including MIR 19, the first authorised Russian siRNA medicinal product).CONCLUSION. Ultimately, siRNA medicinal products are a promising tool for personalised medicine, exhibiting therapeutic potential for a wide range of pathological conditions. Further studies of siRNA medicinal products should aim at improving siRNA production technology to increase their bioavailability and half-life period. In addition, these studies should aim at enhancing delivery systems for these products to mitigate toxicity risks and maximise efficacy.

Ficus carica Linn leaves extract induces cucumber resistance to Podosphaera xanthii by inhibiting conidia and regulating enzyme activity

Cucumbers (Cucumis sativus L.) are highly susceptible to infection by powdery mildew (PM), resulting in a deterioration of cucumber quality. The utilization of chemical control measures can effectively control cucumber PM; however, it may potentially give rise to issues such as environmental pollution, compromised safety, and drug resistance. The urgent need for a green, secure, and efficient strategy to manage cucumber PM necessitates attention. The predominant fungal pathogen causing PM in cucumbers is Podosphaera xanthii (P. xanthii) in this study. The preventive and control efficacy of Ficus carica Linn leaf extract (FLE) against P. xanthii was investigated for the first time. The preventive experiments entail pre-infection spraying of FLE prior to the occurrence of P. xanthii, while the curative experiments involve post-outbreak spraying of FLE. After comprehensive consideration, the optimal approach was determined to be spraying the front of cucumber leaves with a concentration of 0.04 mg/mL FLE in order to effectively control P. xanthii in leaf disc bioassay. The lowest superposition rate from FLE and trisodium phosphate dodecahydrate was 12.86 %, indicating that the impact of FLE on the respiratory metabolism of P. xanthii conidia primarily operates through the hexose monophosphate pathway (HMP). The growth of P. xanthii conidia and mycelium can be inhibited or delayed by FLE. The application of FLE can effectively mitigated chlorophyll loss, suppressed the activities of peroxidase (POD) and polyphenol oxidase (PPO), as well as enhanced the activities of phenylalanine ammonia lyase (PAL), chitinase, and β- 1,3-glucanase. Furthermore, three representative enzyme genes, PAL, POD, and chitinase, were chosen for the purpose of validation. The results suggested that FLE has the ability to modulate the expression of relevant enzyme genes, with peak effects observed after 3–4 days of treatment. The findings offer theoretical support for the advancement of novel botanical pesticides aimed at controlling crop diseases.

Enhancing the Biological Performance of Titanium Alloy through In Situ Modulation of the Surface Nanostructure: Near-Infrared-Responsive Antibacterial Function and Osteoinductivity.

The poor clinical performance of titanium and its alloy implants is mainly attributed to their lack of antibacterial ability and poor osseointegration. The key and challenge lie in how to enhance their osteoinductivity while imparting antibacterial capability. In this study, a titanium oxide metasurface with light-responsive behavior was constructed on the surface of titanium alloy using an alkaline-acid bidirectional hydrothermal method. The effects of the acid type, acid concentration, hydrothermal time, hydrothermal temperature, and subsequent heat treatments on the optical behavior of the metasurface were systematically investigated with a focus on exploring the influence of the metasurface and photodynamic reaction on the osteogenic activity of osteoblasts. Results show that the type of acid and heat treatment significantly affect the light absorption of the titanium alloy surface, with HCl and post-heat-treatment favoring redshift in the light absorption. Under 808 nm near-infrared (NIR) irradiation for 10 min, in vitro antibacterial experiments demonstrate that the antibacterial rate of the metasurface titanium alloy against Staphylococcus aureus and Escherichia coli were 96.87% and 99.27%, respectively. In vitro cell experiments demonstrate that the nanostructure facilitates cell adhesion, proliferation, differentiation, and expression of osteogenic-related genes. Surprisingly, the nanostructure promoted the expression of relevant osteogenic genes of MC3T3-E1 under 808 nm NIR irradiation. This study provides a method for the surface modification of titanium alloy implants.

Synergy under the Sun? Nanoplastics Enhance Estrogenicity of Common UV-Blocker.

Human cells and zebrafish coexposed to nanoplastics and the sunscreen ingredient homosalate showed more plastics in tissues, estrogenic activity, and relevant gene expression changes than they showed after either exposure alone.

Transcriptomics-based Exploration of the Mechanism of Kaempferol in the Treatment of Osteoporosis in Ovariectomized Rats

Objective: We explore the pharmacodynamic targets of kaempferol in treating osteoporosis using transcriptomics and animal experiment. Methods: Firstly, we constructed an ovariectomized rat model (OVX). The anti-osteoporosis effect of kaempferol was evaluated by bone mineral density (BMD) and hematoxylin-eosin staining comprehensively. Moreover, differential genes between groups were screened by RNA sequencing technology (RNA-seq) for transcriptomics and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways enrichment analysis were performed. Finally, partial results of transcriptomics were verified to detect the expression of the relevant gene expression by immunohistochemistry. Results: The pharmacodynamic findings indicated that the administration of kaempferol resulted in an elevation in BMD ( P &lt; .01) and a notable enhancement in tibia microstructural indices in the experimental rats ( P &lt; .01). The transcriptomic analysis revealed that NTN1, LTBP4, GSN, and EBF1 were identified as the principal targets for therapeutic intervention in osteoporosis. The results of animal experiments showed that kaempferol promoted osteogenesis and inhibited bone resorption by downregulating the protein expression of NTN1, LTBP4, GSN, and EBF1 ( P &lt; .01). Conclusion: Kaempferol enhances BMD levels, retards tibial bone loss with structural deterioration in OVX model rats, and promotes bone formation while curbing bone resorption through NTN1, LTBP4, GSN, and EBF1 protein down-regulation.

Gene signatures of endoplasmic reticulum stress and mitophagy for prognostic risk prediction in lung adenocarcinoma.

Genes associated with endoplasmic reticulum stress (ERS) and mitophagy can be conducive to predicting solid tumour prognosis. The authors aimed to develop a prognosis prediction model for these genes in lung adenocarcinoma (LUAD). Relevant gene expression and clinical information were collected from public databases including Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA). A total of 265 differentially expressed genes was finally selected (71 up-regulated and 194 downregulated) in the LUAD dataset. Among these, 15 candidate ERS and mitophagy genes (ATG12, CSNK2A1, MAP1LC3A, MAP1LC3B, MFN2, PGAM5, PINK1, RPS27A, SQSTM1, SRC, UBA52, UBB, UBC, ULK1, and VDAC1) might be critical to LUAD based on the expression analysis after crossing with the ERS and mitochondrial autophagy genes. The prediction model demonstrated the ability to effectively predict the 5-, 3-, and 1-year prognoses of LUAD patients in both GEO and TCGA databases. Moreover, high VDAC1 expression was associated with poor overall survival in LUAD (p<0.001), suggesting it might be a critical gene for LUAD prognosis prediction. Overall, the prognosis model based on ERS and mitophagy genes in LUAD can be useful for evaluating the prognosis of patients with LUAD, and VDAC1 may serve as a promising biomarker for LUAD prognosis.