Cytotoxic and Noncytotoxic Steroidal Constituents of Cryptolepis dubia

Journal of Natural Products, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 14, 2025

(−)-Cryptanoside A (1) was identified previously as a major cytotoxic component of the stems Cryptolepis dubia collected in Laos, which mediates its activity by targeting Na+/K+-ATPase (NKA), with hydrogen bonds formed between 11- and 4′-hydroxy groups NKA being observed docking profile. In continuing investigation, 1 17-epimer, (−)-17-epi-cryptanoside (2), new (+)-2-hydroxyandrosta-4,6-diene-3-one-17-carboxylic acid (3) known (+)-2,21-dihydroxypregna-4,6-diene-3,20-dione or 2-hydroxy-6,7-didehydrocortexone (4) pregnane-type steroids were isolated from C. dubia. addition, (−)-11,4′-di-O-acetylcryptanoside (1a) has been synthesized acetylation 1. The structures these compounds determined analysis their spectroscopic data, inhibitory activities evaluated. contrast to that exhibited potent activities, other largely inactive. Molecular profiles indicated 1–3 1a bind NKA, but some subtle differences interactions may contribute differential potency.

Language: Английский

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Targeting NANOS1 in triple-negative breast cancer: synergistic effects of digoxin and PD-1 inhibitors in modulating the tumor immune microenvironment

Frontiers in Oncology, Journal Year: 2025, Volume and Issue: 14

Published: Jan. 24, 2025

Introduction Triple-negative breast cancer (TNBC) is an aggressive subtype of resistant to endocrine and targeted therapies. Immune checkpoint inhibitors (ICIs) have shown significant efficacy in various cancers. Taraxacum officinale , commonly known as dandelion, has traditionally been used treat breast-related diseases recognized for its beneficial composition low side effects. FDA-approved drugs, having undergone rigorous validation their safety, efficacy, quality, provide a foundation drug repurposing research. Researchers may explore drugs targeting the potential target NANOS1 TOE ( officinal e extract) treatment develop innovative therapeutic strategies. In this context, Dig (Digoxin) AA (Algestone acetophenide) identified candidates further exploration effects application NANOS1. Methods RNA sequencing (RNA-seq) was employed identify targets triple-negative from TOE. Bioinformatics tools, including bc-GenExMiner v4.8, Human Protein Atlas, TIMER database, were utilized identification. Molecular docking studies assessed interacting with these targets, selected candidate drugs. The combination PD-1 evaluated using 4T1 mouse model. Flow cytometry applied assess lymphocyte infiltration tumor immune microenvironment. RNA-seq analysis after silencing by small interfering (siRNA) performed, followed Gene Ontology (GO) Kyoto Encyclopedia Genes Genomes (KEGG) pathway analysis. Validation findings conducted through quantitative PCR Western blot Results inhibited TNBC cell growth, migration, invasion, CCK-8 transwell assays. indicated be due down-regulation. Survival showed lower expression correlated better prognosis. Immunoinfiltration negative correlation between levels activated NK cells. high-affinity binders . Animal experiments inhibitor enhanced immunotherapy TNBC. Discussion study suggest that offer novel approach protein whose down-regulation associated improved patient outcomes. cells highlights role system pathogenesis response treatment. identification provides new direction synergistic effect inhibition observed animal models promising warrants investigation into Overall, identifies therapy suggests could enhance effectiveness improve

Language: Английский

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Nanosurgery and Bioengineered Regenerative Protocols for the Treatment of Hip Osteoarthritis: A Double-Blind Randomized Controlled Trial as an Alternative to Surgical Hip Replacement

Biomedicines, Journal Year: 2025, Volume and Issue: 13(4), P. 987 - 987

Published: April 17, 2025

Introduction: Hip osteoarthritis (HOA) significantly affects mobility and quality of life, with total hip arthroplasty (THA) being a common treatment. However, complications increasing revision rates highlight the need for alternative approaches. This study evaluates efficacy ultrasound-guided nanosurgery bioengineering treatment (NSBT) compared to non-standardized platelet-rich plasma (PRP) patients symptomatic HOA. Methods: A double-blind, randomized trial included 38 referred THA, divided into two groups. The group received NSBT modified PRP enriched somatotropin Strophanthus kombe, while control hyaluronic acid injections without standardized protocol. Treatments were guided by ultrasound, outcomes assessed using Visual Analog Scale (VAS), Western Ontario McMaster Universities Arthritis Index (WOMAC), Harris Score (HHS), range motion (RoM) evaluations over 12 months. Results: showed significant improvements in all clinical outcomes, including reductions VAS scores from 7.8 0.2 (p < 0.0001) WOMAC 76.2 10.5 0.0001). HHS improved 56.4 93.0, RoM substantial gains flexion, external rotation, internal rotation (all p 0.001). demonstrated less pronounced improvements. Conclusions: offers safe effective managing HOA, reducing pain improving joint function potentially delaying or avoiding THA. Further long-term studies are warranted confirm these findings.

Language: Английский

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Na+/K+-ATPase: a multifunctional target in type 2 diabetes and pancreatic islets

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 19, 2025

Type 2 diabetes (T2D) is a widespread metabolic disorder marked by hyperglycemia, arising from insulin resistance and relative deficiency. This review investigates the critical role of Na+/K+-ATPase (NKA), transmembrane protein essential for maintaining cellular ion gradients, in pathophysiology T2D. We provide an overview NKA's biological functions, emphasizing its involvement signaling pathways, secretion, glucose homeostasis. The potential NKA as therapeutic target T2D analyzed, showcasing innovative strategies such activators, gene therapy, stem cell therapy aimed at enhancing activity to achieve better glycemic control. Additionally, multifunctional viability modulating immune responses islet transplantation may offer benefits improving transplant outcomes. By elucidating complex interactions between T2D, this aims shed light on developing novel interventions that meet multifaceted needs individuals suffering chronic condition, ultimately their health

Language: Английский

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Nanosurgery and bioengineered structural regenerative protocols for the treatment of human knee meniscal tears: a double-blind randomized controlled study of a novel regenerative method

Regenerative medicine reports ., Journal Year: 2024, Volume and Issue: 1(2), P. 211 - 221

Published: Dec. 1, 2024

In recent years, global research has increasingly focused on regenerative treatments for meniscal injuries of the knee joint. However, there is still no consensus whether or surgical methods offer better outcomes patients. This double-blind, randomized clinical study involved 32 patients who were into two groups. The group ( n = 16) received a novel treatment which was standardized nanosurgery and bioengineering protocol that included modified platelet-rich plasma using human cell memory intake, while control treated with non-standardized approach involving hyaluronic acid injections under ultrasound guidance without systematized plan orthobiologic delivery. After treatment, mean score changes in Visual Analog Scale, Western Ontario McMaster Universities Osteoarthritis Index, Lysholm scoring significantly greater compared group. These findings suggest method repeatable, objective, well-documented, highly effective treating tears. It offers ensures rapid recovery patients, presenting significant advantage over less structured treatments. supports use protocols settings injuries. Clinical trial registration: ISRCTN15642019

Language: Английский

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Epidemiology, risk factors and mechanism of breast cancer and atrial fibrillation

Cardio-Oncology, Journal Year: 2024, Volume and Issue: 10(1)

Published: Dec. 23, 2024

Language: Английский

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