Molecular Mechanism Of Action Research Articles

UCHL5 promotes hepatocellular carcinoma progression by promoting glycolysis through activating Wnt/β-catenin pathway

Abstract Background Hepatocellular carcinoma (HCC) is highly malignant with a dismal prognosis, although the available therapies are insufficient. No efficient ubiquitinase has been identified as a therapeutic target for HCC despite the complicating role that of proteins ubiquitination plays in the malignant development of HCC. Methods The expression of ubiquitin carboxyl terminal hydrolase L5 (UCHL5) in HCC tumor tissue and adjacent normal tissue was determined using the cancer genome atlas (TCGA) database and was validated using real-time quantitative polymerase chain reaction (RT-qRCR), Western blot and immunohistochemistry (IHC), and the relation of UCHL5 with patient clinical prognosis was explored. The expression of UCHL5 was knocked down and validated, and the effect of UCHL5 on the biological course of HCC was explored using cellular assays. To clarify the molecular mechanism of action of UCHL5 affecting HCC, expression studies of Adenosine triphosphate adenosine triphosphate (ATP), extracellular acidification (ECAR), and glycolysis-related enzymes were performed. The effects of UCHL5 on β-catenin ubiquitination and Wnt signaling pathways were explored in depth and validated using cellular functionalities. Validation was also performed in vivo. Results In the course of this investigation, we discovered that UCHL5 was strongly expressed in HCC at both cellular and tissue levels. The prognosis of patients with high UCHL5 expression is considerably worse than that of those with low UCHL5 expression. UCHL5 has been shown to increase the degree of glycolysis in HCC cells with the impact of stimulating the proliferation and metastasis of HCC cells in both in vivo and in vitro. UCHL5 downregulates its degree of ubiquitination by binding to β-catenin, which activates the Wnt/β-catenin pathway and accelerates HCC cell glycolysis. Thereby promoting the growth of the HCC. Conclusions In summary, we have demonstrated for the first time that UCHL5 is a target of HCC and promotes the progression of hepatocellular carcinoma by promoting glycolysis through the activation of the Wnt/β-catenin pathway. UCHL5 may thus serve as a novel prognostic marker and therapeutic target for the treatment of HCC.

DOX-DNA Interactions on the Nanoscale: In Situ Studies Using Tip-Enhanced Raman Scattering.

Chemotherapeutic anthracyclines, like doxorubicin (DOX), are drugs endowed with cytostatic activity and are widely used in antitumor therapy. Their molecular mechanism of action involves the formation of a stable anthracycline-DNA complex, which prevents cell division and results in cell death. It is known that elevated DOX concentrations induce DNA chain loops and overlaps. Here, for the first time, tip-enhanced Raman scattering was used to identify and localize intercalated DOX in isolated double-stranded calf thymus DNA, and the correlated near-field spectroscopic and morphologic experiments locate the DOX molecules in the DNA and provide further information regarding specific DOX-nucleobase interactions. Thus, the study provides a tool specifically for identifying intercalation markers and generally analyzing drug-DNA interactions. The structure of such complexes down to the molecular level provides mechanistic information about cytotoxicity and the development of potential anticancer drugs.

Insights into Nimbolide molecular crosstalk and its anticancer properties.

Nimbolide, one of the main ingredients constituent of Azadirachta indica (neem) leaf extract, has garnered attention for its potential as an anticancer agent. Its efficacy against various cancers and chemopreventive action has been demonstrated through numerous in vivo and in vitro studies. This updated review aims to comprehensively explore the chemopreventive and anticancer properties of nimbolide, emphasizing its molecular mechanisms of action and potential therapeutic applications in oncology. The review synthesizes evidence from various studies that examine nimbolide's roles in apoptosis induction, anti-proliferation, cell death, metastasis inhibition, angiogenesis suppression, and modulation of carcinogen-metabolizing enzymes. Nimbolide exhibits multifaceted anticancer activities, including the modulation of multiple cell signaling pathways related to inflammation, invasion, survival, growth, metastasis, and angiogenesis. However, its pharmacological development is still in the early stages, mainly due to limited pharmacokinetic and comprehensive long-term toxicological studies. Nimbolide shows promising anticancer and chemopreventive properties, but there is need for systematic preclinical pharmacokinetic and toxicological research. Such studies are essential for establishing safe dosage ranges for first-in-human clinical trials and further advancing nimbolide's development as a therapeutic agent against various cancers. The review highlights the potential of nimbolide in cancer treatment and underscores the importance of rigorous preclinical evaluation to realize its full therapeutic potential.

Recent Advances in Studies of Genomic DNA Methylation and its Involvement in Regulating Drought Stress Response in Crops

As global arid conditions worsen and groundwater resources diminish, drought stress has emerged as a critical impediment to plant growth and development globally, notably causing declines in crop yields and even the extinction of certain cultivated species. Numerous studies on drought resistance have demonstrated that DNA methylation dynamically interacts with plant responses to drought stress by modulating gene expression and developmental processes. However, the precise mechanisms underlying these interactions remain elusive. This article consolidates the latest research on the role of DNA methylation in plant responses to drought stress across various species, focusing on methods of methylation detection, mechanisms of methylation pattern alteration (including DNA de novo methylation, DNA maintenance methylation, and DNA demethylation), and overall responses to drought conditions. While many studies have observed significant shifts in genome-wide or gene promoter methylation levels in drought-stressed plants, the identification of specific genes and pathways involved remains limited. This review aims to furnish a reference for detailed research into plant responses to drought stress through epigenetic approaches, striving to identify drought resistance genes regulated by DNA methylation, specific signaling pathways, and their molecular mechanisms of action.

The mysterious association between adiponectin and endometriosis

Adiponectin is a pleiotropic cytokine predominantly derived from adipose tissue. In addition to its role in regulating energy metabolism, adiponectin may also be related to estrogen-dependent diseases, and many studies have confirmed its involvement in mediating diverse biological processes, including apoptosis, autophagy, inflammation, angiogenesis, and fibrosis, all of which are related to the pathogenesis of endometriosis. Although many researchers have reported low levels of adiponectin in patients with endometriosis and suggested that it may serve as a protective factor against the development of the disease. Therefore, the purpose of this review was to provide an up-to-date summary of the roles of adiponectin and its downstream cytokines and signaling pathways in the aforementioned biological processes. Further systematic studies on the molecular and cellular mechanisms of action of adiponectin may provide novel insights into the pathophysiology of endometriosis as well as potential therapeutic targets.

Anticancer Effects of the Novel Pyrazolyl-Urea GeGe-3

In a screen of over 200 novel pyrazole compounds, ethyl 1-(2-hydroxypentyl)-5-(3-(3-(trifluoromethyl) phenyl)ureido)-1H-pyrazole-4-carboxylate (named GeGe-3) has emerged as a potential anticancer compound. GeGe-3 displays potent anti-angiogenic properties through the presumptive targeting of the protein kinase DMPK1 and the Ca2+-binding protein calreticulin. We further explored the anticancer potential of GeGe-3 on a range of established cancer cell lines, including PC3 (prostate adenocarcinoma), SKMEL-28 (cutaneous melanoma), SKOV-3 (ovarian adenocarcinoma), Hep-G2 (hepatocellular carcinoma), MDA-MB231, SKBR3, MCF7 (breast adenocarcinoma), A549 (lung carcinoma), and HeLa (cervix epithelioid carcinoma). At concentrations in the range of 10 μM, GeGe-3 significantly restricted cell proliferation and metabolism. GeGe-3 also reduced PC3 cell migration in a standard wound closure and trans-well assay. Together, these results confirm the anticancer potential of GeGe-3 and underline the need for more detailed pre-clinical investigations into its molecular targets and mechanisms of action.

Lignan 7-hydroxymatairesinol in the context of post-genomic pharmacology

Objective: to determine the molecular mechanisms of action of 7-hydroxymatairesinol (7(OH)MR), the main lignan of spruce extracts, characterized by oncoprotective and anti-inflammatory properties.Material and methods. The analysis of 7(OH)MR was carried out by chemoinformatic approach using the combinatorial theory of solvability and the topological theory of recognition. The postgenomic approach makes it possible to assess the effect of drugs on genome transcription (transcriptome) and on the proteome as a whole.Results. 7(OH)MP has anti-inflammatory (inhibition of 5-lipoxygenase, matrix metalloproteinase 2, mitogen-activated kinase p38-alpha, leukotriene В4 receptor, prostacyclin receptor), and oncoprotective (antioxidant effect due to inhibition of heme oxygenase-2, inhibition of cyclin-dependent kinases 3 and 4, epidermal growth factor, mTOR protein) pharmacological effects.Conclusion. By reducing the expression of proliferative genes and genes involved in chronic inflammation, the 7(OH)MP molecule inhibits the proliferation of tumor cells. Pharmacoinformatic modeling showed that the anti-inflammatory effects of 7(OH)MR may contribute to increased lifespan in animal models.

Anticancer Therapy with Proteolysis-targeting Chimeras [PROTACs] Targeting Towards the Tumor-microenvironment: Development, Current State and Prospects

Abstract: Targeted protein degradation is a rapidly expanding area that offers hope for novel approaches to combat drug resistance. The creation of heterobifunctional proteolysis-targeting chimeras [PROTACs], a new group of pharmaceutical compounds, has made TPD a useful method for completely getting rid of harmful proteins using regular small-molecule inhibitors. A big plus is that PROTACs can target multi-domain proteins that cannot be broken down. This is the case, particularly for proteins lacking a conserved interaction surface for small-molecule ligands [SMIs] and featuring smooth surfaces. Poor oral bioavailability and pharmacokinetic [PK] and ADMET [absorption, distribution, metabolism, excretion, and toxicity] characteristics are among the long-term issues with traditional PROTACs. Their larger size and more complex structure set them apart from other smallmolecule inhibitors, which is why they are so effective. Clinical studies have been conducted on a plethora of PROTAC compounds in the past 20 years, all with the goal of inducing the degradation of targets relevant to cancer. In this article, we closely examine the major developments and recent advancements in PROTAC technology. We seek to summarize and fully assess PROTAC-based targeted protein degradation studies on "undruggable" targets. Discussing their molecular structure, action mechanism, design concepts, development benefits, and obstacles will help to illustrate the significance of developing highly successful PROTAC-based techniques in treating many illnesses, including cancer treatment resistance.

Intramuscular Botulinum Neurotoxin Serotypes E and A Elicit Distinct Effects on SNAP25 Protein Fragments, Muscular Histology, Spread and Neuronal Transport: An Integrated Histology-Based Study in the Rat

Botulinum neurotoxins E (BoNT/E) and A (BoNT/A) act by cleaving Synaptosome-Associated Protein 25 (SNAP25) at two different C-terminal sites, but they display very distinct durations of action, BoNT/E being short acting and BoNT/A long acting. We investigated the duration of action, spread and neuronal transport of BoNT/E (6.5 ng/kg) and BoNT/A (125 pg/kg) after single intramuscular administrations of high equivalent efficacious doses, in rats, over a 30- or 75-day periods, respectively. To achieve this, we used (i) digit abduction score assay, (ii) immunohistochemistry for SNAP25 (N-ter part; SNAP25N-ter and C-ter part; SNAP25C-ter) and its cleavage sites (cleaved SNAP25; c-SNAP25E and c-SNAP25A) and (iii) muscular changes in histopathology evaluation. Combined in vivo observation and immunohistochemistry analysis revealed that, compared to BoNT/A, BoNT/E induces minimal muscular changes, possesses a lower duration of action, a reduced ability to spread and a decreased capacity to be transported to the lumbar spinal cord. Interestingly, SNAP25C-ter completely disappeared for both toxins during the peak of efficacy, suggesting that the persistence of toxin effects is driven by the persistence of proteases in tissues. These data unveil some new molecular mechanisms of action of the short-acting BoNT/E and long-acting BoNT/A, and reinforce their overall safety profiles.

Analysis and Validation of the Network Pharmacology of the Mechanism of Glycyrrhetinic Acid for the Treatment of High-Altitude Pulmonary Hypertension

Glycyrrhetinic acid (GA) is a pentacyclic triterpene component in Glycyrrhize glabra L, it has demonstrated an inhibitive effect on high-altitude pulmonary hypertension (HAPH), but the molecular action is still not known. We aimed to explore the mechanism of GA for the treatment of HAPH based on network pharmacology and molecular docking method. Cell experiment validation was also conducted. The targets for GA were screened using the Swiss Target Prediction and Batman databases. The HAPH-related targets were obtained using the GeneCards and OMIM databases. The common targets for diseases and drugs were obtained using a Venn diagram. The core targets were screened using the String database. Then, a component-target-disease diagram and protein–protein interaction (PPI) network mutual assistance diagram were developed using Cytoscape3.9.1 software. GO functional and KEGG pathway enrichment analyses were conducted using the Metascape database. Finally, molecular docking of the target and its corresponding active components were performed using Autodock software. A total of 68 common targets for glycyrrhetinic acid high-altitude pulmonary hypertension were screened out. The core targets include PTGS1, MMP1, SERPINA6, and nitric oxide synthase (NOS2), involving PPAR signal pathway, human cytomegalovirus infection, IL-17 signal pathway, proteoglycans in cancer, and other pathways. The molecular docking affinity was −8.4 kcal·mol−1 in average, indicating that GA has a good binding stability with key target proteins. In the PDGF-BB-induced PASMC proliferation model, PASMC proliferation and the p-p38, p38, p-ERK1/2, and ERK1/2 protein expression were inhibited. The pharmacological mechanism of GA for the treatment of HAPH was characterized by multi-target and multi pathway. GA may serve as a promising therapeutic candidate for HAPH but still needs further in vivo/in vitro experiment.

Allosteric Regulation and Inhibition of Coronavirus 3CLpro Revealed by HDX-MS.

Coronavirus (CoV) infections have caused contagious and fatal respiratory diseases in humans worldwide. CoV 3-chymotrypsin-like proteases (3CLpro or Mpro) play an important role in viral maturation, and maintenance of their dimeric conformation is crucial for viral activity. Therefore, allosterically regulated dimerization of 3CLpro can be employed as a drug development target. Here, we investigated the allosteric regulatory mechanism of 3CLpro dimerization by using hydrogen/deuterium exchange coupled with mass spectrometry (HDX-MS) technology. We found that the FLAG tag directly coupled to the N-finger of 3CLpro significantly increased HDX kinetics at the dimer interface, and 3CLpro transformed from a dimer to a monomer. The 3CLpro mutants of SARS-CoV-2, which are monomeric, also exhibited increased deuterium exchange. Binding of the allosteric inhibitor Gastrodenol to most betacoronavirus 3CLpros led to increased allosteric deuterium exchange, resulting in the monomeric conformation of the CoV 3CLpro upon binding. Molecular dynamics (MD) simulation analysis further indicated the molecular mechanism of action of Gastrodenol on CoV 3CLpro: binding of Gastrodenol to SARS-CoV-2 3CLpro destroyed the hydrogen bond in the dimer interface. These results suggest that Gastrodenol may be a potential broad-spectrum anti-betacoronavirus drug.

Ca2+-Dependent Cl− Channels in Vascular Tone Regulation during Aging

Identifying alterations caused by aging could be an important tool for improving the diagnosis of cardiovascular diseases. Changes in vascular tone regulation involve various mechanisms, like NO synthase activity, activity of the sympathetic nervous system, production of prostaglandin, endothelium-dependent relaxing, and contracting factors, etc. Surprisingly, Ca2+-dependent Cl− channels (CaCCs) are involved in all alterations of the vascular tone regulation mentioned above. Furthermore, we discuss these mechanisms in the context of ontogenetic development and aging. The molecular and electrophysiological mechanisms of CaCCs activation on the cell membrane of the vascular smooth muscle cells (VSMC) and endothelium are explained, as well as the age-dependent changes that imply the activation or inhibition of CaCCs. In conclusion, due to the diverse intracellular concentration of chloride in VSMC and endothelial cells, the activation of CaCCs depends, in part, on intracellular Ca2+ concentration, and, in part, on voltage, leading to fine adjustments of vascular tone. The activation of CaCCs declines during ontogenetic development and aging. This decline in the activation of CaCCs involves a decrease in protein level, the impairment of Ca2+ influx, and probably other alterations in vascular tone regulation.

Unraveling the Mechanisms Involved in the Beneficial Effects of Magnesium Treatment on Skin Wound Healing.

The skin wound healing process consists of hemostatic, inflammatory, proliferative, and maturation phases, with a complex cellular response by multiple cell types in the epidermis, dermis, and immune system. Magnesium is a mineral essential for life, and although magnesium treatment promotes cutaneous wound healing, the molecular mechanism and timing of action of the healing process are unknown. This study, using human epidermal-derived HaCaT cells and human normal epidermal keratinocyte cells, was performed to investigate the mechanism involved in the effect of magnesium on wound healing. The expression levels of epidermal differentiation-promoting factors were reduced by MgCl2, suggesting an inhibitory effect on epidermal differentiation in the remodeling stage of the late wound healing process. On the other hand, MgCl2 treatment increased the expression of matrix metalloproteinase-7 (MMP7), a cell migration-promoting factor, and enhanced cell migration via the MEK/ERK pathway activation. The enhancement of cell migration by MgCl2 was inhibited by MMP7 knockdown, suggesting that MgCl2 enhances cell migration which is mediated by increased MMP7 expression. Our results revealed that MgCl2 inhibits epidermal differentiation but promotes cell migration, suggesting that applying magnesium to the early wound healing process could be beneficial.

The role of exosome derived miRNAs in inter-cell crosstalk among insulin-related organs in type 2 diabetes mellitus.

Exosomes are small extracellular vesicles secreted by almost all cell types, and carry diverse cargo including RNA, and other substances. Recent studies have focused exosomal microRNAs (miRNAs) on various human diseases, including type 2 diabetes mellitus (T2DM) and metabolic syndrome (METS) which accompany the occurrence of insulin resistance. The regulation of insulin signaling has connected with some miRNA expression which play a significant regulatory character in insulin targeted cells or organs, such as fat, muscle, and liver. The miRNAs carried by exosomes, through the circulation in the body fluids, mediate all kinds of physiological and pathological process involved in the human body. Studies have found that exosome derived miRNAs are abnormally expressed and cross-talked with insulin targeted cells or organs to affect insulin pathways. Further investigations of the mechanisms of exosomal miRNAs in T2DM will be valuable for the diagnostic biomarkers and therapeutic targets of T2DM. This review will summarize the molecular mechanism of action of the miRNAs carried by exosomes which are secreted from insulin signaling related cells, and elucidate the pathogenesis of insulin resistance to provide a new strategy for the potential diagnostic biomarkers and therapeutic targets for the type 2 diabetes.

Pharmacoinformational, gerontoinformational and chemoreactomic analysis of the molecule of citrulline malate, carnitine, sulbutiamine and meldonium to identify the molecular mechanisms of antiasthenic action

The pathophysiology of asthenia is very complex and is associated with chronic kidney disease, heart failure, chronic obstructive pulmonary disease, sarcopenia, bacterial and viral pathogens, micronutrient nutritional imbalances, hypothyroidism, etc. Asthenia can occur with excessive (for a given patient) physical, mental or mental stress and adaptation disorders or be iatrogenic in nature (in particular, due to taking medications that contribute to increased loss of vitamins and microelements), incl. due to unwanted drug interactions. The complex nature of the pathophysiology of asthenia necessitates the use of a differentiated approach aimed at eliminating the main cause of asthenia in a given patient. If asthenia is associated primarily with disorders of energy metabolism, then the pathophysiological treatment is the use of nutrients that support intracellular synthesis - such as citrulline, citrulline malate, the main mechanisms of action of which are supporting the urea cycle, increasing the excretion of ammonium ions, reducing the concentration lactate in the blood. The paper presents the results of a comparative pharmacoinformatic and chemoreactomic analysis of citrulline, citrulline malate (CM), carnitine, sulbutiamine and meldonium. The profile of pharmacological effects of citrulline/CM was significantly different from the profiles of other molecules. For citrulline/CM, cholinergic, antidepressant, and lipid-modifying effects have been identified and an antiasthenic effect has been suggested when used in the treatment of Duchenne muscular dystrophy and for disorders of carbohydrate metabolism. Unlike other molecules, CM and carnitine do not contribute to the loss of vitamins and minerals. Inhibition of the CM serotonin 5HT3A receptor may improve vestibulation because blockers of 5-HT3 receptors concentrated in neurons of the vestibular apparatus, improves tests of balance and walking in an experiment in mice. A positive dose-dependent effect of citrulline and CM on the lifespan of a number of model organisms has been shown. Chemoreactomic analysis of molecular receptor proteins indicated new molecular mechanisms of the antiasthenic action of CM: inhibition of serotonin receptors, calcium sensor protein receptors, chemokine receptors, lipopolysaccharides (toll receptors), nociceptin, glutamate, orexin, purines and prostanoids, biosynthesis of NF-kB and TNFα.

Approaches to nutritional research using organoids; Fructose treatment induces epigenetic changes in liver organoids

Nutritional researches have successfully used animal models to gain new insights into nutrient action. However, comprehensive descriptions of their molecular mechanisms of action remain elusive as appropriate in vitro evaluation systems are lacking. Organoid models can mimic physiological structures and reproduce in vivo functions, making them increasingly utilized in biomedical research for a better understand physiological and pathological phenomena. Therefore, organoid modeling can be a powerful approach for to understand the molecular mechanisms of nutrient action. The present study aims to demonstrate the utility of organoids in nutritional research by further investigating the molecular mechanisms responsible for the negative effects of fructose intake using liver organoids. Here, we treated liver organoids with fructose and analyzed their gene expression profiles and DNA methylation levels. Microarray analysis demonstrated that fructose-treated organoids exhibited increased selenoprotein p (Sepp1) gene expression, whereas pyrosequencing assays revealed reduced DNA methylation levels in the Sepp1 region. These results were consistent with observations using hepatic tissues from fructose-fed rats. Conversely, no differences in Sepp1 mRNA and DNA methylation levels were observed in two-dimensional cells. These results suggest that organoids serve as an ideal in vitro model to recapitulate in vivo tissue responses and help to validate the molecular mechanisms of nutrient action compared to conventional cellular models.

Molecular Dynamic Simulation To Reveal the Mechanism Underlying MGL-3196 Resistance to Thyroxine Receptor Beta.

Thyroxine receptor beta (TRβ) is a ligand-dependent nuclear receptor that participates in regulating multiple biological processes, particularly playing an important role in lipid metabolism regulation. TRβ is currently a popular therapeutic target for nonalcoholic steatohepatitis (NASH), while no drugs have been approved to treat this disease. MGL-3196 (Resmetirom) is the first TRβ agonist that has succeeded in phase III clinical trials for the treatment of NASH; therefore, studying its molecular mechanism of action is of great significance. In this study, we employed molecular dynamic simulation to investigate the interaction mode between MGL-3196 and TRβ at the all-atom level. More importantly, by comparing the binding patterns of MGL-3196 in several prevalent TRβ mutants, it was identified that the mutations R243Q and H435R located, respectively, around and within the ligand-binding pocket of TRβ cause TRβ to be insensitive to MGL-3196. This indicates that patients with NASH carrying these two mutations may exhibit resistance to the medication of MGL-3196, thereby highlighting the potential impact of TRβ mutations on TRβ-targeted treatment of NASH and beyond.

Andrographis paniculata: A potential supplementary therapy for cardiovascular diseases - A systematic review of its effects and molecular actions

Andrographis paniculata: A potential supplementary therapy for cardiovascular diseases - A systematic review of its effects and molecular actions

Antioxidant Effects and Potential Molecular Mechanism of Action of Diplocyclos palmatus (L.) C. Jeffrey Fruits Based on Systematic Network Pharmacology with Experimental Validation

Oxidative stress arises from an imbalance between the production of reactive oxygen species (ROS) and the ability of biological systems to detoxify these reactive intermediates or repair the resulting damage. Diplocyclos palmatus (D. palmatus) is a medicinal plant, whose fruits has been reported to have antioxidant activity due to its potent bioactive compounds, and holds promise for mitigating oxidative stress and its associated diseases. Therefore, this study aims to elucidate the bioactive compounds present in D. palmatus via Gas Chromatography-Mass Spectrometry (GC-MS) analysis and evaluate their antioxidant activity via different in-vitro antioxidant assays such as, DPPH free radical scavenging assay, ABTS radical scavenging assay, ferric reducing antioxidant power assay, hydroxyl free radical scavenging assay and reactive nitrogen oxide scavenging assay. Furthermore, systematic network pharmacology, molecular docking and molecular dynamics were utilized to identify major bioactive compounds and their interactions with key proteins implicated in oxidative stress to understand the molecular mechanism of action of D. palmatus fruits. The obtained results indicated that the fruit extract had highest antioxidant activity against hydroxyl free radicals (IC50 = 476.76 µg/mL) followed by nitric oxide radicals (IC50 = 509.06 µg/mL), DPPH• (IC50 = 601.88 µg/mL), ABTS•+ (IC50 = 709.37 µg/mL) and FRAP (IC50 = 1141.76 µg/mL). In network pharmacology analysis, bioactive compounds of D. palmatus fruits were found to target numerous major cellular proteins (AKT1, GAPDH, ALB, CASP3, PTGS2, PPARG, STAT3, EGFR, ESR1 and MMP9), with a notable impact on the estrogen signaling pathway. Molecular docking and dynamics analysis further validated the antioxidant potential of D. palmatus fruits. Overall, this integrative study sheds light on the antioxidant potential of D. palmatus fruits and elucidates the molecular mechanisms underpinning their antioxidative actions. These findings not only deepen the understanding of D. palmatus phytochemistry but also highlight its therapeutic potential as a natural antioxidant agent for combating oxidative stress-related disorders.

Roles of lncRNA-MALAT1 in the Progression and Prognosis of Gliomas.

Long noncoding RNAs (lncRNAs) represent a large subgroup of RNA transcripts that lack the function of coding proteins and may be essential universal genes involved in carcinogenesis and metastasis. LncRNA metastasis-associated lung adenocarcinoma transcript 1 (lncRNAMALAT1) is overexpressed in various human tumors, including gliomas. However, the biological function and molecular mechanism of action of lncRNA-MALAT1 in gliomas have not yet been systematically elucidated. Accumulating evidence suggests that the abnormal expression of lncRNA-MALAT1 in gliomas is associated with various physical properties of the glioma, such as tumor growth, metastasis, apoptosis, drug resistance, and prognosis. Furthermore, lncRNAs, as tumor progression and prognostic markers in gliomas, may affect tumorigenesis, proliferation of glioma stem cells, and drug resistance. In this review, we summarize the knowledge on the biological functions and prognostic value of lncRNA-MALAT1 in gliomas. This mini-review aims to deepen the understanding of lncRNA-MALAT1 as a novel potential therapeutic target for the individualized precision treatment of gliomas.