Identification of echinacoside as a tobramycin potentiator againstPseudomonas aeruginosaaggregates

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Feb. 9, 2024

Abstract Cyclic diguanylate (c-di-GMP) is a central biofilm regulator, where increased intracellular levels promote formation and antibiotic tolerance. Targeting the c-di-GMP network promising anti-biofilm approach. Most agents reported previously decreased to eliminate surface-attached biofilms, which did not recapitulate in vivo biofilms well may thus impede their clinical impact. Here, expression profile of genes encoding proteins associated with metabolism was analysed among 32 Pseudomonas aeruginosa strains grown as suspended aggregates synthetic sputum or planktonic cells. A cyclase, SiaD, proved essential for auto-aggregation under -like conditions. Virtual screening against SiaD identified echinacoside an inhibitor, reduced aggregate sizes potentiated efficacy tobramycin established by >80% tested strains. This synergistic effect also observed 3-D alveolar cells infected cytotoxic P. , demonstrating its high potential adjunctive therapy recalcitrant infections.

Language: Английский

---

PTEN neddylation aggravates CDK4/6 inhibitor resistance in breast cancer

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 7, 2024

ABSTRACT The gradual emergence of a novel therapeutic approach lies in the restoration tumor suppressive machinery. PTEN is crucial negative regulator PI3K/Akt signaling pathway. Protein neddylation modification contributes to inactivation and fuels breast cancer progression. Here, we highlight that an elevated level markedly associated with resistance palbociclib, CDK4/6 inhibitor used luminal subtype patients. Mechanistically, activates pathway, more notably, upregulates activity AP-1 transcription factor. Our data showed stabilizes JUND, factor involved complex, by disrupting its interaction E3 ubiquitin ligase ITCH. Consequently, activated JUND leads release cytokines chemokines, which turn may drive inflammatory microenvironment, potentially contributing drug resistance. Then, identified Echinacoside as potent both vivo vitro XIAP, responsible for neddylation. Combination effectively overcome palbociclib treatment. These findings targeting promising strategy restoring suppressor overcoming

Language: Английский

---

Echinacoside inhibits hepatocellular carcinoma progression by targeting the miR-30c-5p/FOXD1/KLF12 axis

Technology and Health Care, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 16

Published: Aug. 29, 2024

BACKGROUND: Hepatocellular carcinoma (HCC) is the third leading cause of cancer-attributed mortality and primary liver malignancy in world. Echinacoside a phenylethanoid glycoside derived from traditional Chinese medicinal herbs which possessed multiple health benefits on humans, including anti-tumor effects. OBJECTIVE: This study aimed to demonstrate function echinacoside HCC progression involvement miR-30c-5p/FOXD1/KLF12 axis. METHODS: The HepG2 cells were treated by different dose echinacoside, miR-30c-5p mimic, inhibitor, FOXD1 overexpression lentiviruses or siRNA individually simultaneously. cell invasion migration measured transwell assay. RNA protein levels tested RT-PCR western blot, respectively. regulatory Forkhead box D1 (FOXD1), Krüppel-like factor 12 (KLF12) was luciferase reporter assay or/and ChIP Meanwhile, cancer lung metastasis mice model used examine functions vivo. Moreover, correlations among miR-30c-5p, FOXD1, KLF12, prognosis analyzed using clinical sample TCGA database. RESULTS: Based both vitro vivo investigations, we found that could inhibit migration, invasiveness, tumor metastasis, associated with enhanced Furthermore, through analyzing interactions intermediate molecules, revealed KLF12üere clinically relevant each other patients, correlated prognosis, regulated contribute inhibition progression. CONCLUSIONS: These findings suggest progression, mechanism related abovementioned molecules might serve as prospective biomarkers for prognosis.

Language: Английский

---

Phytochemistry, Mechanisms, and Preclinical Studies of Echinacea Extracts in Modulating Immune Responses to Bacterial and Viral Infections: A Comprehensive Review

Antibiotics, Journal Year: 2024, Volume and Issue: 13(10), P. 947 - 947

Published: Oct. 9, 2024

Background: Echinacea species, particularly purpurea, angustifolia, and pallida, are renowned for their immunomodulatory, antibacterial, antiviral properties. Objectives: This review explores the mechanisms by which echinacea herbal extracts modulate immune responses, focusing on effects both innate adaptive immunity in bacterial viral infections. Results: Key bioactive compounds, such as alkamides, caffeic acid derivatives, flavonoids, polysaccharides, contribute to these effects. These compounds enhance cell activity, including macrophages natural killer cells, stimulating cytokine production phagocytosis. The antibacterial activity of against respiratory pathogens (Streptococcus pneumoniae, Haemophilus influenzae, Legionella pneumophila) skin (Staphylococcus aureus, Propionibacterium acnes) is reviewed, well its efficacy viruses like herpes simplex, influenza, rhinovirus. Echinacea’s potential a complementary treatment alongside conventional antibiotics antivirals discussed, context antibiotic resistance emerging threats. Conclusions: Challenges associated with variability phytochemical content need standardized extraction processes also addressed. provides comprehensive overview echinacea’s therapeutic outlines future directions research, clinical trials dosage optimization.

Language: Английский

---