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1.
Plants (Basel) ; 13(13)2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38999593

RESUMO

Bassia indica (Wight) A.J. Scott is an Indian origin plant with documented medicinal and nutritional value, but has not been fully characterized yet. The present study was designed to establish pharmacognostic standards for the proper identification of the B. indica plant and its chemical characterization. The plant was standardized with World Health Organization (WHO) standardization tools and chemically characterized by Fourier transform infrared spectroscopy (FTIR) and gas chromatography-mass spectroscopy (GC-MS) analysis. Antibacterial potential was assessed by the zone of inhibition and minimum inhibitory concentration (MIC), and molecular docking studies were also performed. Pharmacognostic evaluation established the macroscopic and microscopic parameters for the identification of whole plant and its powder. Physicochemical parameters were also set forth while quantitative phytochemical analysis showed that the ethyl acetate fraction had the highest quantity of phenols, flavonoids, and tannins. FTIR analysis showed several functional groups such as phenols, alkanes, and alcohols while 55 phytochemicals were identified in the GC-MS analysis of the crude fraction. The crude extract and other fractions showed marked antibacterial activity, while the ethyl acetate fraction showed the least MIC (1.95-31.25 mg/mL). Phytochemicals identified in the GC-MS showed good molecular docking interactions against the DNA gyrase subunit B of bacteria with binding energies ranging from -4.2 to -9.4 kcal/mol. The current study describes the pharmacognostic characterization and phytochemical profiling of B. indica and provides scientific evidence to support its use in infections.

2.
PLoS One ; 18(9): e0286256, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37713409

RESUMO

FAM3C/ILEI is an important factor in epithelial-to-mesenchymal transition (EMT) induction, tumor progression and metastasis. Overexpressed in many cancers, elevated ILEI levels and secretion correlate with poor patient survival. Although ILEI's causative role in invasive tumor growth and metastasis has been demonstrated in several cellular tumor models, there are no available transgenic mice to study these effects in the context of a complex organism. Here, we describe the generation and initial characterization of a Tet-ON inducible Fam3c/ILEI transgenic mouse strain. We find that ubiquitous induction of ILEI overexpression (R26-ILEIind) at weaning age leads to a shortened lifespan, reduced body weight and microcytic hypochromic anemia. The anemia was reversible at a young age within a week upon withdrawal of ILEI induction. Vav1-driven overexpression of the ILEIind transgene in all hematopoietic cells (Vav-ILEIind) did not render mice anemic or lower overall fitness, demonstrating that no intrinsic mechanisms of erythroid development were dysregulated by ILEI and that hematopoietic ILEI hyperfunction did not contribute to death. Reduced serum iron levels of R26-ILEIind mice were indicative for a malfunction in iron uptake or homeostasis. Accordingly, the liver, the main organ of iron metabolism, was severely affected in moribund ILEI overexpressing mice: increased alanine transaminase and aspartate aminotransferase levels indicated liver dysfunction, the liver was reduced in size, showed increased apoptosis, reduced cellular iron content, and had a fibrotic phenotype. These data indicate that high ILEI expression in the liver might reduce hepatoprotection and induce liver fibrosis, which leads to liver dysfunction, disturbed iron metabolism and eventually to death. Overall, we show here that the novel Tet-ON inducible Fam3c/ILEI transgenic mouse strain allows tissue specific timely controlled overexpression of ILEI and thus, will serve as a versatile tool to model the effect of elevated ILEI expression in diverse tissue entities and disease conditions, including cancer.


Assuntos
Anemia , Longevidade , Camundongos , Animais , Longevidade/genética , Cirrose Hepática/genética , Anemia/genética , Ferro , Camundongos Transgênicos
3.
EMBO Mol Med ; 15(7): e16758, 2023 07 10.
Artigo em Inglês | MEDLINE | ID: mdl-37226685

RESUMO

FAM3C/ILEI is an important cytokine for tumor progression and metastasis. However, its involvement in inflammation remains elusive. Here, we show that ILEI protein is highly expressed in psoriatic lesions. Inducible keratinocyte-specific ILEI overexpression in mice (K5-ILEIind ) recapitulates many aspects of psoriasis following TPA challenge, primarily manifested by impaired epidermal differentiation and increased neutrophil recruitment. Mechanistically, ILEI triggers Erk and Akt signaling, which then activates STAT3 via Ser727 phosphorylation. Keratinocyte-specific ILEI deletion ameliorates TPA-induced skin inflammation. A transcriptomic ILEI signature obtained from the K5-ILEIind model shows enrichment in several signaling pathways also found in psoriasis and identifies urokinase as a targetable enzyme to counteract ILEI activity. Pharmacological inhibition of urokinase in TPA-induced K5-ILEIind mice results in significant improvement of psoriasiform symptoms by reducing ILEI secretion. The ILEI signature distinguishes psoriasis from healthy skin with uPA ranking among the top "separator" genes. Our study identifies ILEI as a key driver in psoriasis, indicates the relevance of ILEI-regulated genes for disease manifestation, and shows the clinical impact of ILEI and urokinase as novel potential therapeutic targets in psoriasis.


Assuntos
Psoríase , Ativador de Plasminogênio Tipo Uroquinase , Camundongos , Animais , Ativador de Plasminogênio Tipo Uroquinase/genética , Ativador de Plasminogênio Tipo Uroquinase/metabolismo , Citocinas/metabolismo , Queratinócitos , Transdução de Sinais
4.
Polymers (Basel) ; 13(16)2021 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-34451208

RESUMO

Plant-mediated synthesis of nanoparticles exhibits great potential to minimize the generation of chemical waste through the utilization of non-toxic precursors. In this research work, we report the synthesis of magnesium oxide (MgO) and cobalt oxide (Co3O4) nanoparticles through a green approach using Manilkara zapota leaves extract, their surface modification by polyaniline (PANI), and antifungal properties against Aspergillus niger. Textural and structural characterization of modified and unmodified metal oxide nanoparticles were evaluated using FT-IR, SEM, and XRD. The optimal conditions for inhibition of Aspergillus niger were achieved by varying nanoparticles' concentration and time exposure. Results demonstrate that PANI/MgO nanoparticles were superior in function relative to PANI/Co3O4 nanoparticles to control the growth rate of Aspergillus niger at optimal conditions (time exposure of 72 h and nanoparticles concentration of 24 mM). A percentage decrease of 73.2% and 65.1% in fungal growth was observed using PANI/MgO and PANI/Co3O4 nanoparticles, respectively, which was higher than the unmodified metal oxide nanoparticles (67.5% and 63.2%).

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