Bioactive Compounds from Kalanchoe Genus Potentially Useful for the Development of New Drugs

Life, Год журнала: 2023, Номер 13(3), С. 646 - 646

Опубликована: Фев. 26, 2023

The genus Kalanchoe Adans. (Crassulaceae) is native to Madagascar and comprises 145 species, being naturalized in the tropics cultivated worldwide. In addition having ornamental value, several species are commonly used popular medicine for treatment of inflammatory conditions, wounds, gastric ulcers, other diseases. great importance reflected on its acknowledgment by traditional alternative health systems organizations, as well growing number papers reporting pharmacological properties extracts isolated compounds from Kalanchoe. Among these properties, we highlight anti-inflammatory, antitumor, wound healing, antiulcer, muscle relaxing properties. These activities attributed mostly flavonoids bufadienolides, main secondary metabolites reported extracts. While bufadienolides generally related cytotoxic activities, anti-inflammatory healing agents. This review provides up date information perspectives bioactive that potentially useful development new drugs. It includes not only a discussion advantages source compounds, but also gaps, opportunities, challenges translate acquired knowledge into innovation drug development.

Язык: Английский

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Preclinical Evaluation of [18F]P4B-2412 as Phosphodiesterase 4B Radioligand for Positron Emission Tomography Imaging

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Янв. 16, 2025

Phosphodiesterase 4B (PDE4B) plays a critical role in cAMP hydrolysis and is highly expressed brain regions associated with neuroinflammation central nervous system (CNS) disorders. Selective PDE4B radioligands hold significant potential for elucidating disease mechanisms, such as those Parkinson's schizophrenia, enabling target occupancy measurements. In this study, we developed [ 18 F]P4B-2412, novel PDE4B-selective radioligand, evaluated its utility positron emission tomography imaging (PET). F]P4B-2412 was synthesized high radiochemical yield (27.2%), excellent purity (99%), favorable molar activity (66.2 ± 2.5 GBq/μmol. vitro autoradiography dynamic PET demonstrated specificity rodent regions, blocking studies confirming negligible interaction PDE4D. also exhibited robust vivo metabolic stability. These results establish promising agent visualizing activity, offering valuable tool investigating advancing CNS drug development.

Язык: Английский

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Rutaecarpine alleviates hepatic ischemia‒reperfusion injury in liver transplantation by inhibiting inflammatory response and oxidative stress

Frontiers in Pharmacology, Год журнала: 2025, Номер 16

Опубликована: Фев. 3, 2025

Background Donation after circulatory death (DCD) livers are limited by mandatory warm ischemia and more susceptible to ischemia‒reperfusion injury (IRI). Inflammation oxidative stress play key roles in the development of hepatic IRI, Rutaecarpine (Rut) has anti-inflammatory anti-oxidative effects. The aim this study was investigate whether Rut can alleviate IRI liver transplantation (LT) explore underlying mechanisms. Methods Rat DCD LT oxygen-glucose deprivation/reoxygenation (OGD/R) cell models were established clarify effect on IRI. molecules involved hepatoprotective effects identified through joint analysis data from patients drug targets. target further validated silico , vivo vitro experiments. Results significantly alleviated dysfunction, pathological injury, apoptosis improved survival rate rats subjected LT. In addition, inhibited inflammatory response stress. also had similar OGD/R-induced hepatocyte injury. Mechanistically, bioinformatics experiments revealed that PDE4B may be a which exerts its protective effect, molecular docking cellular thermal shift assay confirmed result. function studied via gene intervention technology, results showed aggravate Furthermore, overexpression abrogated Conclusion alleviates targeting inhibit inflammation These findings highlight potential as candidate for treatment undergoing

Язык: Английский

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Glutamine metabolism-related genes and immunotherapy in nonspecific orbital inflammation were validated using bioinformatics and machine learning

BMC Genomics, Год журнала: 2024, Номер 25(1)

Опубликована: Янв. 17, 2024

Abstract Background Nonspecific orbital inflammation (NSOI) is an idiopathic, persistent, and proliferative inflammatory condition affecting the orbit, characterized by polymorphous lymphoid infiltration. Its pathogenesis progression have been linked to imbalances in tumor metabolic pathways, with glutamine (Gln) metabolism emerging as a critical aspect cancer. Metabolic reprogramming known influence clinical outcomes various malignancies. However, comprehensive research on metabolism's significance NSOI lacking. Methods This study conducted bioinformatics analysis identify validate potential glutamine-related molecules (GlnMgs) associated NSOI. The discovery of GlnMgs involved intersection differential expression set 42 candidate GlnMgs. biological functions pathways identified were analyzed using GSEA GSVA. Lasso regression SVM-RFE methods hub genes assessed diagnostic efficacy fourteen correlation between characteristics was also examined. levels validated datasets GSE58331 GSE105149. Results Fourteen related identified, including FTCD, CPS1, CTPS1, NAGS, DDAH2, PHGDH, GGT1, GCLM, GLUD1, ART4, AADAT, ASNSD1, SLC38A1, GFPT2. Biological function indicated their involvement responses extracellular stimulus, mitochondrial matrix, lipid transport. performance these distinguishing showed promising results. Conclusions successfully NSOI, providing insights into novel biomarkers for avenues monitoring disease progression.

Язык: Английский

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Bioinformatic validation and machine learning-based exploration of purine metabolism-related gene signatures in the context of immunotherapeutic strategies for nonspecific orbital inflammation

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Март 28, 2024

Background Nonspecific orbital inflammation (NSOI) represents a perplexing and persistent proliferative inflammatory disorder of idiopathic nature, characterized by heterogeneous lymphoid infiltration within the region. This condition, marked aberrant metabolic activities its cellular constituents, starkly contrasts with equilibrium found in healthy cells. Among myriad pathways integral to metabolism, purine metabolism emerges as critical player, providing building blocks for nucleic acid synthesis, such DNA RNA. Despite significance, contribution Purine Metabolism Genes (PMGs) pathophysiological landscape NSOI remains mystery, highlighting gap our understanding disease’s molecular underpinnings. Methods To bridge this knowledge gap, study embarked on an exploratory journey identify validate PMGs implicated NSOI, employing comprehensive bioinformatics strategy. By intersecting differential gene expression analyses curated list 92 known PMGs, we aimed pinpoint those potential roles NSOI. Advanced methodologies, including Gene Set Enrichment Analysis (GSEA) Variation (GSVA), facilitated deep dive into biological functions associated these PMGs. Further refinement through Lasso regression Support Vector Machine-Recursive Feature Elimination (SVM-RFE) enabled identification key hub genes evaluation their diagnostic prowess Additionally, relationship between relevant clinical parameters was thoroughly investigated. corroborate findings, analyzed data from datasets GSE58331 GSE105149, focusing seven identified potentially crucial pathology. Results Our investigation unveiled (ENTPD1, POLR2K, NPR2, PDE6D, PDE6H, PDE4B, ALLC) intimately connected Functional shed light involvement processes peroxisome targeting sequence binding, seminiferous tubule development, ciliary transition zone organization. Importantly, capabilities demonstrated promising efficacy distinguishing non-affected states. Conclusions Through rigorous analyses, unveils novel biomarker candidates elucidating pathogenesis. These discoveries not only enhance at level but also pave way innovative approaches monitor progression, offering beacon hope individuals afflicted enigmatic condition.

Язык: Английский

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Identification of cis-sQTL demonstrates genetic associations and functional implications of inflammatory processes in Nelore cattle muscle tissue

Mammalian Genome, Год журнала: 2025, Номер 36(1), С. 106 - 117

Опубликована: Янв. 18, 2025

Язык: Английский

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Lipid Nanoparticle-Mediated Delivery of Microrna-124 Reduces Neuroinflammation

Опубликована: Янв. 1, 2025

Язык: Английский

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Microglial circDlg1 modulates neuroinflammation by blocking PDE4B ubiquitination-dependent degradation associated with Alzheimer's disease

Theranostics, Год журнала: 2025, Номер 15(8), С. 3401 - 3423

Опубликована: Фев. 24, 2025

Background: Abnormal activation of microglia occurs in the early stage Alzheimer's disease (AD) and leads to subsequent neuroinflammation major AD pathologies. Circular RNAs (circRNAs) are emerging as great potential therapeutic targets AD. However, extent circRNAs entwined underlying mechanism microglia-driven remain elusive. Methods: The circular RNA Dlg1 (circDlg1) was identified using circRNA microarray screening magnetic-isolated APP/PS1 mice. CircDlg1 expression mice patients validated by FISH. Flow cytometry immunostaining were conducted explore roles circDlg1 microglia. Adeno-associated virus 9 preparations for interfering with microglial microinjected into mouse lateral ventricle influences on response, Y-maze, novel object recognition Morris water maze tasks performed assess cognitive performance. pulldown assays, mass spectrometry analysis, immunoprecipitation, co-immunoprecipitation validate regulatory mechanisms circDlg1. Results: A observed elevated isolated from increased intracerebral patients. Microglia-specific knockdown remarkably ameliorated recruitment envelopment amyloid-β (Aβ), mitigated neuroinflammation, prevented decline Mechanistically, interfered interaction between phosphodiesterase 4b (PDE4B) Smurf2, an E3 ubiquitin ligase PDE4B. formed ternary complex protected PDE4B ubiquitination-dependent degradation via unique N-terminal targeting domain, thus consequently decreasing cAMP levels. We further confirmed that downregulation significantly activated PKA/CREB anti-inflammatory pathway protein levels Conclusion: microglia-upregulated tightly involves determining fate Microglial loss promotes protective response Aβ deposition relieves suggesting a strategy specifically

Язык: Английский

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BI 1015550 Improves Silica-Induced Silicosis and LPS-Induced Acute Lung Injury in Mice

Molecules, Год журнала: 2025, Номер 30(6), С. 1311 - 1311

Опубликована: Март 14, 2025

Silicosis is an interstitial lung disease (ILD) caused by prolonged inhalation of silica particles. Acute injury (ALI) a critical clinical syndrome involving bilateral infiltration and acute hypoxic respiratory failure. However, there currently no effective treatment for these two diseases. Previous research has established that cyclic adenosine monophosphate (cAMP) pivotal in the pathogenesis silicosis injury. Phosphodiesterase 4 (PDE4) hydrolase enzyme cAMP, BI 1015550, as inhibitor PDE4B, expected to be candidate drug treating both. 1015550 shown certain anti-inflammatory anti-fibrotic properties systemic sclerosis-associated (SSc-ILD) idiopathic pulmonary fibrosis (IPF), but lack on In this research, we successfully synthesized autonomously demonstrated it could significantly improve inflammation silica-induced mouse model. Furthermore, found also alleviate Lipopolysaccharide (LPS)-induced The mechanism action may involve regulation cAMP-related signaling pathways.

Язык: Английский

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Integrating Single-cell and Bulk RNA-seq to Construct a Metastasis-related Model for Evaluating Immunotherapy and Chemotherapy in Uveal Melanoma

Current Medicinal Chemistry, Год журнала: 2024, Номер 31(42), С. 7030 - 7042

Опубликована: Янв. 4, 2024

Metastasis is a major cause of death in UM, highlighting the need to use highly specific and sensitive prognostic markers identify patients with risk developing metastasis.

Язык: Английский

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