RESUMEN
BACKGROUND: Several WRKY transcription factors (TFs), including CaWRKY6, CaWRKY22, CaWRKY27, and CaWRKY40 are known to govern the resistance of pepper (Capsicum annuum L.) plants to Ralstonia solanacearum infestation (RSI) and other abiotic stresses. However, the molecular mechanisms underlying these processes remain elusive. METHODS: This study functionally described CaWRKY3 for its role in pepper immunity against RSI. The roles of phytohormones in mediating the expression levels of CaWRKY3 were investigated by subjecting pepper plants to 1 mM salicylic acid (SA), 100 µM methyl jasmonate (MeJA), and 100 µM ethylene (ETH) at 4-leaf stage. A virus-induced gene silencing (VIGS) approach based on the Tobacco Rattle Virus (TRV) was used to silence CaWRKY3 in pepper, and transiently over-expressed to infer its role against RSI. RESULTS: Phytohormones and RSI increased CaWRKY3 transcription. The transcriptions of defense-associated marker genes, including CaNPR1, CaPR1, CaDEF1, and CaHIR1 were decreased in VIGS experiment, which made pepper less resistant to RSI. Significant hypersensitive (HR)-like cell death, H2O2 buildup, and transcriptional up-regulation of immunological marker genes were noticed in pepper when CaWRKY3 was transiently overexpressed. Transcriptional activity of CaWRKY3 was increased with overexpression of CaWRKY6, CaWRKY22, CaWRKY27, and CaWRKY40, and vice versa. In contrast, Pseudomonas syringae pv tomato DC3000 (Pst DC3000) was easily repelled by the innate immune system of transgenic Arabidopsis thaliana that overexpressed CaWRKY3. The transcriptions of defense-related marker genes like AtPR1, AtPR2, and AtNPR1 were increased in CaWRKY3-overexpressing transgenic A. thaliana plants. CONCLUSION: It is concluded that CaWRKY3 favorably regulates phytohormone-mediated synergistic signaling, which controls cell death in plant and immunity of pepper plant against bacterial infections.
Asunto(s)
Capsicum , Regulación de la Expresión Génica de las Plantas , Enfermedades de las Plantas , Reguladores del Crecimiento de las Plantas , Inmunidad de la Planta , Proteínas de Plantas , Ralstonia solanacearum , Factores de Transcripción , Ralstonia solanacearum/fisiología , Capsicum/genética , Capsicum/inmunología , Capsicum/microbiología , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Enfermedades de las Plantas/microbiología , Enfermedades de las Plantas/inmunología , Enfermedades de las Plantas/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Reguladores del Crecimiento de las Plantas/metabolismo , Ciclopentanos/metabolismo , Resistencia a la Enfermedad/genética , Oxilipinas/metabolismo , Ácido Salicílico/metabolismo , Etilenos/metabolismo , Silenciador del Gen , Acetatos/farmacologíaRESUMEN
Type 2 diabetes mellitus is characterized by hyperglycemia and insulin resistance. It is spreading around the globe like a pandemic. Major factors behind the development of diabetes can be genetics, environmental factors, dietary choices and obesity. Many medicinal plants have anti-diabetic potential. This study has investigated the anti-diabetic effect of curry leaves extract. This study also investigated the chemical characterization of curry leaves. Phytochemicals including saponins, tannins, alkaloids, flavonoids, phenols and glycosides were also investigated. Encapsulated 5mg per kg of the body weight and 10mg per kg of the body weight were given to treatment groups I and II. Random blood sugar, fasting blood sugar and HbA1c of 45 diabetic female adults were measured on the 0-day and 45th days. All results were analyzed using the two-sample t-test in IBM SPSS Statistics 20. Curry leaves contained moisture (24.1±1.78)%, ash (17.82±2.13)%, nitrogen free extract (36.12±3.52)%, crude protein (8.32±0.83)%, crude fiber (6.98±2.31)% and crude fat (6.87±0.21)%. Mineral analysis showed that magnesium and calcium were major minerals present in curry leaves. Curry leaves extract contained saponins 2.71±0.23, flavonoids 7.84±0.42, tannins 0.91±0.09, glycosides 0.17±0.01, phenols 3.89±0.12, alkaloids 2.01±0.87. These phytochemicals were expressed in mg/100 g of the sample. Curry leaf extract showed a significant (p<0.05) reduction in fasting blood sugar, random blood sugar and glycated hemoglobin in both treatment groups.
Asunto(s)
Alcaloides , Diabetes Mellitus Tipo 2 , Murraya , Saponinas , Adulto , Humanos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Glucemia/metabolismo , Murraya/química , Taninos/análisis , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Extractos Vegetales/análisis , Alcaloides/análisis , Fitoquímicos/uso terapéutico , Fitoquímicos/análisis , Flavonoides/uso terapéutico , Flavonoides/análisis , Fenoles/análisis , Suplementos Dietéticos/análisis , Glicósidos , Saponinas/uso terapéutico , Saponinas/análisis , Peso Corporal , Hojas de la Planta/químicaRESUMEN
Hyperglycemia is a condition often observed in diabetics, dyslipidemia and obese. It is a major factor behind the development of diabetes and the reasons can be genetics, environmental factors, dietary choices and obesity. Many medicinal plants have anti-diabetic potential. This study investigated the anti-hyperglycemic effect of apple peel extract. This study also investigated the chemical characterization of apple peel. Phytochemicals including total phenolics and flavonoids were determined. Encapsulated 350mg/day was given to treatment groups. Random blood sugar, fasting blood sugar and HbA1c of 45 diabetic female adults was measured on the 0-day and 45th day. Results showed that apple peel contained moisture (14.71±3.57)%, ash (17.82±2.13)%, nitrogen free extract (32.12±3.52)%, crude protein (6.89±0.83)%, crude fiber (19.17±0.21)% and crude fat (9.91±2.31)%. Findings showed that apple peel contains magnesium (6.61±1.088), calcium (8.17±0.32), zinc (14.08±1.21) and potassium (67.21±1.86). These findings were shown in mg in kg. Apple peel extract contained total phenolic content (TPC) of 8.14±1.07 and total phenolic content (TFC) of 4.89±1.81. Apple peel extract showed a significant reduction in all blood parameters of hyperglycemia. All results were significant at p<0.05.
Asunto(s)
Hiperglucemia , Malus , Humanos , Malus/química , Frutas/química , Antioxidantes/química , Glucemia/análisis , Fenoles/análisis , Suplementos Dietéticos , Hiperglucemia/tratamiento farmacológicoRESUMEN
Hypercholesterolemia is a condition with elevated cholesterol and lipid profile. It is the leading reason behind myocardial infarction and coronary heart disease. It is observed in young people as well due to a sedentary lifestyle. Triphala powder has a hypolipidemic and anti-hypercholesterolemia effect. This study was designed to investigate the effect of triphala powder against hypercholesterolemia. This study also examined Triphala powder's chemical composition. Total phenolic and flavonoid content were examined. Encapsulated 400 mg and 600 mg Triphala powder were given to treatment groups I and II. Lipid profile parameters were measured and compared at 0 weeks and 10th weeks in all groups. All results were analyzed using ANOVA in IBM SPSS Statistics 20. Results of proximate analyses have shown that Okra pod powder contains moisture 12.27%, ash 11.25%, nitrogen-free extract 45.93%, crude protein 13.37%, crude fat 2.95% and crude fiber 14.23%. Mineral analysis showed that iron and manganese are major minerals in triphala powder. Triphala powder showed a significant reduction in lipid profile parameters in hypercholesterolemia. All results are taken significantly at p<0.05.
Asunto(s)
Hipercolesterolemia , Hiperlipidemias , Humanos , Masculino , Adolescente , Hipercolesterolemia/tratamiento farmacológico , Polvos , Extractos Vegetales/uso terapéutico , LípidosRESUMEN
Citrus sinensis is an important member of the genus Citrus which contains phenolic compounds and bioflavonoids which have antihyperlipidemic and antiatherogenic effects. It also has the potential to reduce oxidative stress. To investigate the antihyperlipidemic effect of orange peel powder was encapsulated and analyzed in hyperlipidemic patients. Results showed that it contains moisture (12.2%), ash content (7.9%), crude fat (0.78%), crude protein (12.37%) and crude fiber (13.2%). Total phenolic content and total flavonoid content were observed as 163.17 mg and 17.23mg in quercetin equivalent per gram a dry weight basis. Furthermore, the Orange peel powder was given in the form of medicinal capsules to hyperlipidemia male subjects. The experimental groups (G1 and G2) were given orange peel powder in capsules 400mg/d to the G1 group and 800mg/d to the G2 group for the time of 45 days. The serum lipid profile of patients was measured before and after the experimental trial. The result showed that G1 and G2 showed a decrease in plasma lipid parameters and increased high-density lipoprotein content in blood substantially as compared to G0. Thus, it was concluded from the results that orange peel powder depicts a significant impact on treating hyperlipidemia.
Asunto(s)
Citrus sinensis , Citrus , Hiperlipidemias , Humanos , Masculino , Cápsulas , Citrus/química , Citrus sinensis/química , Flavonoides , Hiperlipidemias/tratamiento farmacológico , Hipolipemiantes/farmacología , Hipolipemiantes/uso terapéutico , Lípidos , Fenoles , PolvosRESUMEN
Hepatocellular carcinoma (HCC) is a common type of liver cancer and is a leading cause of death worldwide. Signal transducer and activator of transcription 3 (STAT3) is involved in HCC progression, migration, and suppression of apoptosis. This study investigates the apoptotic effect of the dietary antioxidant (n-3 PUFAs) on HepG2 cells and analyzes the underlying molecular mechanisms of this effect both in vivo and in vitro. In vivo study: Seventy-five adult male albino rats were divided into three groups (n = 25): Group I (control): 0.9% normal saline, intraperitoneal. Group II: N-Nitrosodiethylamine (200 mg/kg b.wt) intraperitoneal, followed by phenobarbital 0.05% in drinking water. Group III: as group II followed by n-3 PUFAs intubation (400 mg/kg/day). In vivo study: liver specimens for biochemical, histopathological, and immunohistochemical examination. In vitro study: MTT assay, cell morphology, PCR, Western blot, and immunohistochemical analysis. n-3 PUFAs significantly improved the histopathologic features of HCC and decreased the expression of anti-apoptotic proteins. Further, HepG2 cells proliferation was suppressed through inhibition of the STAT3 signaling pathway, cyclin D1, and Bcl-2 activity. Here we report that n-3 PUFAs may be an ideal cancer chemo-preventive candidate by targeting STAT3 signaling, which is involved in cell proliferation and apoptosis.
Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Masculino , Apoptosis , Carcinoma Hepatocelular/metabolismo , Línea Celular Tumoral , Proliferación Celular , Neoplasias Hepáticas/patología , Transducción de Señal , Factor de Transcripción STAT3/metabolismo , Animales , RatasRESUMEN
The Moroccan flora abounds and is an important reserve of medicinal plants. Nigella sativa and Lepidium sativum are plants that are widely used in traditional medicine for their multiple therapeutic properties. The current study aims to highlight the biological activities that can justify and valorize the use of these plants. Flavonoids, total phenols, condensed tannins, and sugars were determined. The biological activities tested were antioxidant by determining the IC50 (defined as the concentration of an antioxidant required to decrease the initial concentration by 50%; inversely related to the antioxidant capacity), hemagglutination, and hemolytic activities. Phytochemical quantification of the seed extracts indicated that the total phenol content was largely similar for both plants and in the order of 10 mg GAE (Gallic acid equivalent)/g. On the other hand, L. sativum seeds registered a higher content of flavonoids (3.09 ± 0.04 mg QE (quercetin equivalent)/g) as compared to Nigella saliva (0.258 ± 0.058). Concerning condensed tannins, N. saliva seeds present a higher amount with a value of 7.2 ± 0.025 mg/g as compared to L. sativum (1.4 ± 0.22 mg/g). Concerning the total sugar content, L. sativum shows a higher content (67.86 ± 0.87 mg/g) as compared to N. sativa (58.17 ± 0.42 mg/g); it is also richer in mucilage with a content of 240 mg as compared to 8.2 mg for N. saliva. Examination of the antioxidant activity using a DPPH (2.2-diphenyl 1-pycrilhydrazyl) test revealed that the EButOH (n-butanol extract) and EAE (ethyl acetate extract) extracts were the most active, with IC50 values of 48.7 and 50.65 µg/mL for the N. sativa extracts and 15.7 and 52.64 µg/mL for the L. sativum extracts, respectively. The results of the hemagglutination activity of the different extracts of the two plants prepared in the PBS (phosphate-buffered saline) medium showed significant agglutination for the L. sativum extract (1/50) compared to the N. sativa extract (1/20). An evaluation of the hemolytic effect of the crude extract of the studied seeds on erythrocytes isolated from rat blood incubated in PBS buffer compared to the total hemolysis induced by distilled water showed a hemolysis rate of 54% for Nigella sativa and 34% for L. sativum. In conclusion, the two plants studied in the current work exhibited high antioxidant potential, which could explain their beneficial properties.
Asunto(s)
Nigella sativa , Proantocianidinas , Ranunculaceae , 1-Butanol , Adyuvantes Inmunológicos , Animales , Antioxidantes/química , Flavonoides/química , Ácido Gálico/análisis , Hemólisis , Lepidium sativum , Nigella sativa/química , Fenol/análisis , Fenoles/química , Fosfatos/análisis , Fitoquímicos/análisis , Fitoquímicos/farmacología , Extractos Vegetales/química , Proantocianidinas/análisis , Quercetina/análisis , Ratas , Semillas/química , Azúcares/análisis , Agua/análisisRESUMEN
Upon inflammation, natural killer (NK) cells undergo metabolic changes to support their high energy demand for effector function and proliferation. The metabolic changes are usually accompanied by an increase in the expression of nutrient transporters, leading to increased nutrient uptake. Among various cytokines inducing NK cell proliferation, the mechanisms underlying the effect of interleukin (IL)-18 in promoting NK cell proliferation are not completely understood. Here, we demonstrate that IL-18 is a potent cytokine that can enhance the expression of the nutrient transporter CD98/LAT1 for amino acids independently of the mTORC1 pathway and thereby induce a dramatic metabolic change associated with increased proliferation of NK cells. Notably, treatment of IL-18-stimulated NK cells with leucine activates the metabolic sensor mTORC1, indicating that the high expression of amino acid transporters induces amino acid-driven mTORC1 activation. Inhibition of the amino acid transporter CD98/LAT1 abrogated the leucine-driven mTORC1 activation and reduced NK cell effector function. Taken together, our study identified a novel role of IL-18 in up-regulating nutrient transporters on NK cells and thereby inducing metabolic changes, including the mTORC1 activation by amino acids.
Asunto(s)
Aminoácidos/metabolismo , Proteína-1 Reguladora de Fusión/metabolismo , Interleucina-18/fisiología , Células Asesinas Naturales/metabolismo , Diana Mecanicista del Complejo 1 de la Rapamicina/metabolismo , Regulación hacia Arriba/fisiología , Animales , Proliferación Celular , Células Cultivadas , Ratones , Ratones Endogámicos C57BLRESUMEN
New 2-thioxopyrimidinone derivatives (A1-A10) were synthesized in 87-96% yields via a simple three-component condensation reaction. These compounds were screened extensively through in vitro assays for antioxidant and antibacterial investigations. The DPPH assays resulted in the excellent potency of A6-A10 as antioxidants with IC50 values of 0.83 ± 0.125, 0.90 ± 0.77, 0.36 ± 0.063, 1.4 ± 0.07, and 1.18 ± 0.06 mg/mL, which were much better than 1.79 ± 0.045 mg/mL for the reference ascorbic acid. These compounds exhibited better antibacterial potency against Klebsiella with IC50 values of 2 ± 7, 1.32 ± 8.9, 1.19 ± 11, 1.1 ± 12, and 1.16 ± 11 mg/mL for A6-A10. High-throughput screenings (HTS) of these motifs were carried out including investigation of drug-like behaviors, physiochemical property evaluation, and structure-related studies involving DFT and metabolic transformation trends. The radical scavenging ability of the synthesized motifs was validated through molecular docking studies through ligand-protein binding against human inducible nitric oxide synthase (HINOS) PDB ID: 4NOS, and the results were promising. Furthermore, the antiviral capability of the compounds was examined by in silico studies using two viral proteins PDB ID: 6Y84 and PDB ID: 6LU7. Binding poses of ligands were discussed, and amino acids in the protein binding pockets were investigated, where the tested compounds showed much better binding affinities than the standard inhibitors, proving to be suitable leads for antiviral drug discovery. The stabilities of the molecular docked complexes in real systems were validated by molecular dynamics simulations.
RESUMEN
This study focused on developing novel pyridine-3-carboxamide analogs to treat bacterial wilt in tomatoes caused by Ralstonia solanacearum. The analogs were synthesized through a multistep process and their structures confirmed using spectroscopy. Molecular docking studies identified the most potent analog from the series. A specific analog, compound 4a, was found to significantly enhance disease resistance in tomato plants infected with R. solanacearum. The structure-activity relationship analysis showed the positions and types of substituents on the aromatic rings of compounds 4a-i strongly influenced their biological activity. Compound 4a, with a chloro group at the para position on ring C and hydroxyl group at the ortho position on ring A, was exceptionally effective against R. solanacearum. When used to treat seeds, the analogs displayed remarkable efficacy, especially compound 4a which had specific activity against bacterial wilt pathogens. Compound 4a also promoted vegetative and reproductive growth of tomato plants, increasing seed germination and seedling vigor. In plants mechanically infected with bacteria, compound 4a substantially reduced the percentage of infection, pathogen quantity in young tissue, and disease progression. The analogs were highly potent due to their amide linkage. Molecular docking identified the best compounds with strong binding affinities. Overall, the strategic design and synthesis of these pyridine-3-carboxamide analogs offers an effective approach to targeting and controlling R. solanacearum and bacterial wilt in tomatoes.
Asunto(s)
Simulación del Acoplamiento Molecular , Enfermedades de las Plantas , Piridinas , Ralstonia solanacearum , Solanum lycopersicum , Solanum lycopersicum/microbiología , Solanum lycopersicum/efectos de los fármacos , Ralstonia solanacearum/efectos de los fármacos , Enfermedades de las Plantas/microbiología , Piridinas/farmacología , Piridinas/química , Relación Estructura-Actividad , Antibacterianos/farmacología , Antibacterianos/síntesis química , Antibacterianos/química , Resistencia a la EnfermedadRESUMEN
Masitinib is an orally acceptable tyrosine kinase inhibitor that is currently investigated under clinical trials against cancer, asthma, Alzheimer's disease, multiple sclerosis and amyotrophic lateral sclerosis. A recent study confirmed the anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) activity of masitinib through inhibition of the main protease (Mpro) enzyme, an important pharmacological drug target to block the replication of the coronavirus. However, due to the adverse effects and lower potency of the drug, there are opportunities to design better analogues of masitinib. Herein, we substituted the N-methylpiperazine group of Masitinib with different chemical moieties and evaluated their drug-likeness and toxicities. The filtered analogues were subjected to molecular docking studies which revealed that the analogues with substituents methylamine in M10 (CID10409602), morpholine in M23 (CID59789397) and 4-methylmorpholine in M32 (CID143003625) have a stronger affinity to the drug receptor compared to masitinib. The molecular dynamics (MD) simulation analysis reveals that the identified analogues alter the mobility, structural compactness, accessibility to solvent molecules, and the number of hydrogen bonds in the native target enzyme. These structural alterations can help explain the inhibitory mechanisms of these analogues against the target enzyme. Thus, our studies provide avenues for the design of new masitinib analogues as the SARS-CoV-2 Mpro inhibitors.
RESUMEN
Background: Monkeypox Virus (MPV) is the cause of zoonotic disease characterized by skin-eruption with pus cell formation and lymphadenopathy. This virus belongs to the Orthopoxvirus genus with DNA as its genetic material. Previously, this infection was reported from Africa and occasionally from USA and UK. However, recently there is a sudden surge of infection in non-epidemic countries and a new strain of MPVhas been discovered. Therefore it is important to revisit the phylogeny of MPV with the addition of new strains. Recently WHO also stressed the need of developing vaccines for new strains. In this scenario we have two objectives for this study -first, to reveal the exact phylogenetic position of the 2022 strain and second, to identify specific peptides which may be used for vaccine development in the future. Methods: The phylogenetic analysis was done with the help of Bayesian phylogeny. The dN/dS calculation was performed based on DNA polymerase genes of selected MPV strains. The peptidyl-epitope was searched in MPV2022/2 SLO strain with the help of several algorithms implemented in Allergen FP v.1.0, NetMHCII 2.3, MHCpred and Toxin Pred. The structure prediction of the proteins and peptides was performed through Hpepdock. The quality of the structures was validated through the Ramachandran plot. The molecular dynamics and simulation were performed through Gromacs software. The interaction between peptide and protein was assessed through Ligplot software. Results: The phylogenetic analysis revealed that the considered 2022 MPVstrains were close to the USA strains. The evolutionary analysis showed the volatile nature of the genome. Moreover, 9-mer peptide sequence was identified as an epitope for vaccine development. Conclusions: The emergence of more virulent strains in near future may not be ruled out. Immunocompromised patients are more susceptible to this virus hence sub-unit vaccine is a better choice than a recombinant or attenuated vaccine against monkeypox. We have identified a small stretch of specific peptide which may be used for developing a subunit vaccine against this virus.
RESUMEN
Rising soil salinity is a major concern for agricultural production worldwide, particularly in arid and semi-arid regions. To improve salt tolerance and the productivity of economic crop plants in the face of future climatic changes, plant-based solutions are required to feed the continuously increasing world population. In the present study, we aimed to ascertain the impact of Glutamic-acid-functionalized iron nanoparticles (Glu-FeNPs) on two varieties (NM-92 and AZRI-2006) of mung beans with different concentrations (0, 40 mM, 60 mM, and 80 mM) of osmotic stress. The result of the study showed that vegetative growth parameters such as root and shoot length, fresh and dry biomass, moisture contents, leaf area, and the number of pods per plant were significantly decreased with osmotic stress. Similarly, biochemicals such as protein, chlorophylls, and carotenes contents also significantly declined under induced osmotic stress. The application of Glu-FeNPs significantly (p ≤ 0.05) restored both the vegetative growth parameters and biochemical contents of plants under osmotic stress. The pre-sowing treatment of seeds with Glu-FeNPs significantly ameliorated the tolerance level of Vigna radiata to osmotic stress by optimizing the level of antioxidant enzymes and osmolytes such as superoxide dismutase (SOD), peroxidase (POD), and proline contents. Our finding indicates that Glu-FeNPs significantly restore the growth of plants under osmotic stress via enhancing photosynthetic activity and triggering the antioxidation system of both varieties.
RESUMEN
Head and neck squamous cell carcinoma (HNSC) is one of the most lethal malignancies around the globe. Due to its complex nature, the diagnostic and prognostic signatures of HNSC remain poorly understood. This study was launched to identify signature genes and their signaling pathways related to the development of HNSC. In the current study, we retrieved the GSE53819 dataset from the Gene Expression Omnibus (GEO) database to determine the differentially expressed genes (DEGs) using the "Limma" R package. Adjusted P values P < 0.05 and |logFC| ≥ 1 were selected as the filtering conditions. To identify hub genes, the protein-protein interaction (PPI) network construction of the DEGs was performed using STRING. We further used UALCAN, GEPIA, OncoDB, GENT2, MEXPRESS, and HPA databases for the expression, validation, survival, and methylation analyses of the hub genes. The cBioPortal tool was used to investigate the genetic alterations in hub genes. CancerSEA, TIMER, DAVID, ENCORI, and DrugBank were also used to explore a few more hub gene-associated parameters. Lastly, HOK, FaDu, and SCC25 cell lines were used to validate hub gene expression via RNA sequencing (RNA-seq) technique. A total of top 250 DEGs were selected for detailed analysis in this study. From these DEGs, prognostic and diagnostic associated four hub genes, which could serve as potential molecular biomarkers and therapeutic targets in HNSC patients were identified. Four hub genes, including down-regulated DNAH1 and DNALI1, while up-regulated DNAH9 and CCDC151 were strongly implicated in HNSC. We also validated the same expression pattern of the hub genes using RNA-seq analysis in HNSC and normal cell lines. Moreover, this study also revealed some novel links between DNAH1, DNALI1, DNAH9, and CCDC151 expression and genetic alterations, promoter methylation status, immune cell infiltration, miRNAs, gene enrichment terms, and various chemotherapeutic drugs. In conclusion, we indicated four hub genes (DNAH1, DNALI1, DNAH9, and CCDC151) and their associated signaling pathways, which may improve our understanding of HNSC and could be used as new therapeutic targets.
RESUMEN
BACKGROUND: Previously reported breast invasive carcinoma (BRIC) biomarkers have compromised utility because of their heterogeneity-specific behaviors. The goal of this study was to find BRIC biomarkers that could be used in spite of the heterogeneity barrier. METHODS: Previously reported BRIC-linked hub genes were obtained from the literature via a search technique. A protein-protein interaction (PPI) network of the extracted hub genes was constructed, visualized, and analyzed to explore the top six real hub genes. Following this, real hub genes' expression profiling was carried out using various TCGA data sources and RNA sequencing (RNA-seq) of BT 20 and HMEC cell lines to uncover the tumor-driver roles of the real hub genes. RESULTS: In total, 124 BRIC-linked hub genes were collected from the literature via the search technique. From these collected hub genes, a total of 6 genes, including Centrosomal protein of 55 kDa (CEP55), Kinesin Family Member 2C (KIF2C), kinesin family member 20A (KIF20A), Ribonucleotide Reductase Regulatory Subunit M2 (RRM2), Aurora A Kinase (AURKA), and Protein Regulator of cytokinesis 1 (PRC1) were determined to be the real hub genes. Via expression profiling and validation analyses, we documented the overexpression of CEP55, KIF2C, KIF20A, RRM2, AURKA, and PRC1 real hub genes in BRIC patients with different clinical variables. Further correlational analyses showed diverse associations among real hub genes' expression and other important parameters, including promoter methylation status, genetic alteration, overall survival (OS), relapse-free survival (RFS), tumor purity, CD8+ T, CD4+ T immune cell infiltration, and different mutant genes across BRIC samples. Finally, in this work, we investigated several transcription factors (TFS), microRNAs, and therapeutic medicines related to the real hub genes that have great therapeutic potential. CONCLUSION: In conclusion, we discovered six real hub genes, which may be employed as novel potential biomarkers for BRIC patients with different clinical parameters.
RESUMEN
BACKGROUND: Although evidence regarding pituitary tumor-transforming 3, pseudogene (PTTG3P) involvement in human cancers has been acquired via human and animal model-based molecular studies, there is a lack of pan-cancer analysis of this gene in human tumors. METHODS: Tumor-causing effects of PTTG3P in 24 human tumors were explored using The Cancer Genome Atlas (TCGA) datasets from different bioinformatics databases and applying in silico tools such as The University of ALabama at Birmingham CANcer (UALCAN), Human Protein Atlas (HPA), Kaplan Meier (KM) plotter, cBioPortal, Search Tool for the Retrieval of Interacting Genes/Proteins (STRING), Cytoscape, Database for Annotation, Visualization, and Integrated Discovery (DAVID), Tumor IMmune Estimation Resource (TIMER), and Comparative Toxicogenomics Database (CTD). Then, via in vitro experiments, including RNA sequencing (RNA-seq) and targeted bisulfite sequencing (bisulfite-seq), expression and promoter methylation levels of PTTG3P were verified in cell lines. RESULTS: The PTTG3P expression was overexpressed across 23 malignancies and its overexpression was further found significantly effecting the overall survival (OS) durations of the esophageal carcinoma (ESCA) and head and neck cancer (HNSC) patients. This important information helps us to understand that PTTG3P plays a significant role in the development and progression of ESCA and HNSC. As for PTTG3P functional mechanisms, this gene along with its other binding partners was significantly concentrated in "Oocyte meiosis", "Cell cycle", "Ubiquitin mediated proteolysis", and "Progesterone-mediated oocyte maturation". Moreover, ESCA and HNSC tissues having the higher expression of PTTG3P were found to have lower promoter methylation levels of PTTG3P and higher CD8+ T immune cells level. Additionally, PTTG3P expression-regulatory drugs were also explored in the current manuscript for designing appropriate treatment strategies for ESCA and HNSC with respect to PTTG3P expression. CONCLUSION: Our pan-cancer based findings provided a comprehensive account of the oncogenic role and utilization of PTTG3P as a novel molecular biomarker of ESCA and HNSC.
RESUMEN
OBJECTIVES: Prominin 2 (PROM2) gene has been reported as a molecular biomarker of human cancers; however, its role is still controversial. This study was therefore arranged to seek the role of PROM2 in different cancers with Bioinformatics and in vitro analyses. METHODS: A combination of bioinformatics and molecular experiments. RESULTS: Through the utilization of Bioinformatics analysis, it was observed that in 19 out of the 24 human cancers studied, there was a significant increase in the expression of PROM2 compared to the respective control samples. Additionally, the overexpression of PROM2 was linked specifically to a decrease in overall survival (OS) among breast cancer (BRCA), lung adenocarcinoma (LUAD), and uterine corpus endometrial carcinoma (UCEC) patients. Furthermore, advanced molecular investigations were conducted, encompassing RNA sequencing (RNA-seq) as well as targeted bisulfite sequencing (bisulfite-seq) assessments of PROM2. These analyses were performed across an array of lung cancer cell lines (A549, ABC-1, EBC-1, and LK-2) and a normal control lung cell line (MRC-9). Results of these analysis revealed overexpression and reduced methylation of PROM2 within lung cancer cell lines, relative to the corresponding control cell line. This suggests that PROM2 assumes a substantial function in the advancement and course of BRCA, LUAD, and UCEC cancers. Subsequent pathway analysis revealed that genes enriched by PROM2 are actively engaged in four pivotal pathways. Additionally, intriguing associations were observed between PROM2 expression, tumor purity, infiltration of CD8+ T immune cells, and genetic modifications. Moreover, we also predicted a few MicroRNAs (miRNAs), transcription factors (TFs), and potential drugs that could help to understand and better manage these cancers via designing appropriate therapies targeting PROM2. CONCLUSION: Via this study, we effectively revealed PROM2 overexpression as a potential diagnostic and prognostic biomarker of survival in BRCA, LUAD, and UCEC.
RESUMEN
One of the most prevalent chronic conditions affecting older men is benign prostatic hyperplasia (BPH), causing severe annoyance and embarrassment to patients. The pathogenesis of BPH has been connected to epithelial proliferation, inflammation, deranged redox balance, and apoptosis. Diacerein (DIA), the anthraquinone derivative, is a non-steroidal anti-inflammatory drug. This study intended to investigate the ameliorative effect of DIA on the prostatic histology in testosterone-induced BPH in rats. BPH was experimentally induced by daily subcutaneous injection of testosterone propionate for four weeks. The treated group received DIA daily for a further two weeks after induction of BPH. Rats' body and prostate weights, serum-free testosterone, dihydrotestosterone, and PSA were evaluated. Prostatic tissue was processed for measuring redox balance and histopathological examination. The BPH group had increased body and prostate weights, serum testosterone, dihydrotestosterone, PSA, and oxidative stress. Histologically, there were marked acinar epithelial and stromal hyperplasia, inflammatory infiltrates, and increased collagen deposition. An immunohistochemical study showed an increase in the inflammatory TNF-α and the proliferative PCNA markers. Treatment with DIA markedly decreased the prostate weight and plasma hormones, improved tissue redox balance, repaired the histological changes, and increased the proapoptotic caspase 3 expression besides the substantial reduction in TNF-α and PCNA expression. In conclusion, our study underscored DIA's potential to alleviate the prostatic hyperplastic and inflammatory changes in BPH through its antioxidant, anti-inflammatory, antiproliferative, and apoptosis-inducing effects, rendering it an effective, innovative treatment for BPH.
Asunto(s)
Hiperplasia Prostática , Testosterona , Animales , Masculino , Ratas , Antiinflamatorios/farmacología , Apoptosis , Dihidrotestosterona , Oxidación-Reducción , Extractos Vegetales/farmacología , Antígeno Nuclear de Célula en Proliferación/metabolismo , Antígeno Prostático Específico , Hiperplasia Prostática/inducido químicamente , Hiperplasia Prostática/tratamiento farmacológico , Ratas Sprague-Dawley , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
BACKGROUND: Oncogenic processes in cancer are often characterized by dysregulation of critical genes. Our study focused on the minichromosome maintenance 10 replication initiation factor (MCM10) gene's expression and its potential diagnostic and prognostic implications in pan-cancer. METHOD: Leveraging large-scale genomic datasets, and experimental validation we embarked on a comprehensive analysis to shed light on the diagnostic and prognostic role of MCM10. RESULTS: Our findings underscore the wide-ranging up-regulation of MCM10 across 24 major cancer types, positioning it as a ubiquitous player in tumorigenesis. Significantly, MCM10 up-regulation was strongly associated with poorer overall survival in Kidney Renal Papillary Cell Carcinoma (KIRP), Liver Hepatocellular Carcinoma (LIHC), and Lung Adenocarcinoma (LUAD), emphasizing its potential as a valuable prognostic marker in these cancers. While genetic mutations often drive oncogenic processes, our mutational analysis revealed the relative stability of MCM10 in KIRP, LIHC, and LUAD. This suggests that epigenetic (hypomethylation) and non-mutational regulatory mechanisms predominantly govern MCM10 expression in these cancer types. Further analyses demonstrated positive correlations between MCM10 expression and immune cell infiltration, particularly CD8+ T cells and CD4+ T cells, offering insights into the gene's influence on the tumor immune microenvironment. Additionally, pathway enrichment analysis highlighted MCM10-associated genes' involvement in crucial signaling pathways, such as the cell cycle, DNA replication, and repair. Exploring the therapeutic potential, we examined important drugs capable of regulating MCM10 expression, opening doors to personalized treatment strategies. CONCLUSION: Our study elucidates the multifaceted roles of MCM10 in KIRP, LIHC, and LUAD. Its pervasive up-regulation, prognostic significance, epigenetic regulation, and influence on the immune microenvironment provide valuable insights into these cancers. This research contributes to the growing body of evidence surrounding MCM10 and invites further investigation, validation, and potential translational efforts to harness its clinical relevance.
RESUMEN
Natural killer (NK) cells are predominant innate lymphocytes that initiate the early immune response during infection. NK cells undergo a metabolic switch to fuel augmented proliferation and activation following infection. Tumor necrosis factor-alpha (TNFα) is a well-known inflammatory cytokine that enhances NK cell function; however, the mechanism underlying NK cell proliferation in response to TNFα is not well established. Here, we demonstrated that upon infection/inflammation, NK cells upregulate the expression of TNF receptor 2 (TNFR2), which is associated with increased proliferation, metabolic activity, and effector function. Notably, IL-18 can induce TNFR2 expression in NK cells, augmenting their sensitivity toward TNFα. Mechanistically, TNFα-TNFR2 signaling upregulates the expression of CD25 (IL-2Rα) and nutrient transporters in NK cells, leading to a metabolic switch toward aerobic glycolysis. Transcriptomic analysis revealed significantly reduced expression levels of genes involved in cellular metabolism and proliferation in NK cells from TNFR2 KO mice. Accordingly, our data affirmed that genetic ablation of TNFR2 curtails CD25 upregulation and TNFα-induced glycolysis, leading to impaired NK cell proliferation and antiviral function during MCMV infection in vivo. Collectively, our results delineate the crucial role of the TNFα-TNFR2 axis in NK cell proliferation, glycolysis, and effector function.