Transcriptomics Unveil Canonical and Non-Canonical Heat Shock-Induced Pathways in Human Cell Lines DOI Creative Commons

Andrew Reinschmidt,

Luis Solano,

Yonny Chavez

et al.

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

Published: Dec. 23, 2024

Abstract The cellular stress response (CSR) is a conserved mechanism that protects cells from environmental and physiological stressors. heat shock (HSR), critical component of the CSR, utilizes molecular chaperones to mitigate proteotoxic caused by elevated temperatures. We hypothesized while canonical HSR pathways are across cell types, specific lines may exhibit unique transcriptional responses shock. To test this, we compared transcriptomic HEK293, HepG2, HeLa under control conditions immediately following after an 8-hour recovery period. RNA sequencing revealed activation pathways, including unfolded protein response, alongside enrichment non-canonical “Receptor Ligand Activity” pathway all lines. Cell line-specific variations were also observed, with HepG2 displaying more uniquely expressed genes expression levels (fold changes) shared conditions. Validation qPCR confirmed key within time points. These findings provide insights into context-specific aspects HSR, contributing comprehensive understanding mechanisms mammalian cells.

Language: Английский

Identification of a New Pentafluorosulfanyl-Substituted Chalcone with Activity Against Hepatoma and Human Parasites DOI Creative Commons

Alessandra Viperino,

Michael Höpfner,

Nicole Edel

et al.

Pharmaceuticals, Journal Year: 2025, Volume and Issue: 18(1), P. 50 - 50

Published: Jan. 3, 2025

Background/Objectives: New drugs are required for the treatment of liver cancers and protozoal parasite infections. Analogs known anticancer active antileishmanial 2′,4′,6′-trimethoxychalcone SU086 were prepared investigated. Methods: The chalcones according to Claisen–Schmidt condensation protocol analyzed. They tested activity against two cancer cell lines (HepG2 HuH-7) parasites (Toxoplasma gondii Leishmania major). Unspecific toxicity expression Hsp90 Hsp70 upon analyzed in cells. Results: A new chalcone, 2′,4′,6′-trimethoxy-3-pentafluorosulfanylchalcone (246TMP-3SF5), with a pentafluorosulfanyl (SF5) substituent showed pronounced activities cells T. which superior parent chalcone these models. In contrast, its anthracene analog 2′,4′,6′-trimethoxy-9-anthracenylchalcone (246TMP-Anth) most L. major promastigotes. SF5-substituted behaved like inhibitor 17-AAG upregulated Conclusions: has potential become drug therapy hepatoma toxoplasmosis.

Language: Английский

Citations

0
Mechanisms of thermal, acid, desiccation and osmotic tolerance of Cronobacter spp. DOI

Yanfei Yan,

Mengyuan Cao,

Jiaqi Ma

et al.

Critical Reviews in Food Science and Nutrition, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 23

Published: Jan. 3, 2025

Cronobacter spp. exhibit remarkable resilience to extreme environmental stresses, including thermal, acidic, desiccation, and osmotic conditions, posing significant challenges food safety. Their thermotolerance relies on heat shock proteins (HSPs), genomic islands, enhanced DNA repair mechanisms, metabolic adjustments, ensuring survival under high-temperature conditions. Acid tolerance is achieved through internal pH regulation, acid efflux pumps, proteins, allowing in acidic matrices the gastrointestinal tract. Desiccation mediated by accumulation of protective osmolytes like trehalose, stabilizing membranes withstand dryness, especially dry products. Similarly, stress supported compatible solutes such as trehalose glycine betaine, along with adaptations balance pressures. These mechanisms highlight adaptability diverse environments. Moreover, exposure sublethal heat, osmotic, dry, may induce homologous or cross-resistance, complicating control strategies. Understanding these essential mitigate risks spp., powdered infant formula (PIF), ensure

Language: Английский

Citations

0
Association of single nucleotide polymorphisms rs7459185 of the HSPβ1 gene and the risk of hematological toxicity in lung cancer DOI
Óscar Muñoz Muñoz,

B.D. Delgado León,

Elías Gomis Sellés

et al.

Lung Cancer, Journal Year: 2025, Volume and Issue: 200, P. 108103 - 108103

Published: Jan. 23, 2025

Language: Английский

Citations

0
Exosome: an overview on enhanced biogenesis by small molecules DOI

Amir Bavafa,

Maryam Izadpanahi,

Elham Hosseini

et al.

Naunyn-Schmiedeberg s Archives of Pharmacology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 25, 2025

Language: Английский

Citations

0
From cold to hot: mechanisms of hyperthermia in modulating tumor immunology for enhanced immunotherapy DOI Creative Commons

M. Marc Abreu,

Alberto F. Chocron,

David M. Smadja

et al.

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

Published: Feb. 28, 2025

The emergence of immunotherapies has revolutionized cancer treatment by leveraging the immune system to target malignancies, offering new hope where traditional therapies often fall short. Within this context, hyperthermia (HT) re-emerged as a promising adjunctive treatment, capable enhancing effectiveness radiotherapy, chemotherapy, and immunotherapy. HT influences both innate adaptive systems, activity cells such neutrophils, NK cells, dendritic while also modulating tumor microenvironment (TME) promote immunogenic cell death (ICD) reduce immunosuppressive conditions. These effects contribute transformation immunologically “cold” tumors into “hot” tumors, making them more susceptible immune-mediated destruction. Furthermore, can amplify efficacy checkpoint inhibitors (ICIs) improving infiltration, inducing damage-associated molecular pattern (DAMP) release, antigen presentation. Preclinical clinical studies support combination with ICIs, demonstrating improved outcomes in otherwise resistant tumors. However, full therapeutic potential different technologies allowing apply remains be fully understood, further research is needed optimize protocols, explore differential impacts local versus whole-body hyperthermia, identify biomarkers for patient stratification. This review underscores multifaceted role immunity its significantly enhance

Language: Английский

Citations

0
The Protective Role of Heat Shock Proteins against Stresses in Animal Breeding DOI Open Access
Sirui Liu,

Yinkun Liu,

Endong Bao

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(15), P. 8208 - 8208

Published: July 27, 2024

Heat shock proteins (HSPs) play an important role in all living organisms under stress conditions by acting as molecular chaperones. The expression of different HSPs during varies depending on their protective functions and anti-apoptotic activities. application improves the efficiency decreases economic cost animal breeding. By upregulating HSPs, feed supplements can improve tolerance farm animals. In addition, high is often a feature tumor cells, inhibiting promising novel method for killing these cells treating cancers. present review, findings previous research breeding veterinary medicine are summarized, knowledge actions animals briefly discussed.

Language: Английский

Citations

3
PU-H71 (NSC 750424): a molecular masterpiece that targets HSP90 in cancer and beyond DOI Creative Commons
Sameh Saber, Rasha Abdelhady, Mai A. Elhemely

et al.

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: Nov. 5, 2024

Heat shock protein 90 (HSP90) is a pivotal molecular chaperone with multifaceted roles in cellular health and disease. Herein, we explore how HSP90 orchestrates stress responses, particularly through its partnership heat factor 1 (HSF-1). PU-H71, selective inhibitor of HSP90, demonstrates significant potential cancer therapy by targeting wide array oncogenic pathways. By inducing the degradation multiple client proteins, PU-H71 disrupts critical signaling pathways such as MAPK, PI3K/Akt, JAK/STAT, EGFR, mTOR, which are essential for cell survival, proliferation, metastasis. We examined impact on combating triple-negative breast enhancing effectiveness carbon-ion beam therapy, offering new avenues treatment. Furthermore, dual inhibition HSP90A HSP90B1 proves highly effective context myeloma, providing fresh hope patients this challenging malignancy. delve into to induce apoptosis B-cell lymphomas that rely Bcl6 highlighting relevance realm hematologic cancers. Shifting our focus hepatocellular carcinoma, innovative approaches chemotherapy. Moreover, current review elucidates capacity suppress glial activation paving way developing novel therapeutic strategies neuroinflammatory disorders. Additionally, present report also suggests promising role JAK2-dependent myeloproliferative neoplasms. Eventually, sheds more light functions well benefit an diseases, laying foundations development could achieve better treatment outcomes.

Language: Английский

Citations

1
Transcriptomics Unveil Canonical and Non-Canonical Heat Shock-Induced Pathways in Human Cell Lines DOI Creative Commons

Andrew Reinschmidt,

Luis Solano,

Yonny Chavez

et al.

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

Published: Dec. 23, 2024

Abstract The cellular stress response (CSR) is a conserved mechanism that protects cells from environmental and physiological stressors. heat shock (HSR), critical component of the CSR, utilizes molecular chaperones to mitigate proteotoxic caused by elevated temperatures. We hypothesized while canonical HSR pathways are across cell types, specific lines may exhibit unique transcriptional responses shock. To test this, we compared transcriptomic HEK293, HepG2, HeLa under control conditions immediately following after an 8-hour recovery period. RNA sequencing revealed activation pathways, including unfolded protein response, alongside enrichment non-canonical “Receptor Ligand Activity” pathway all lines. Cell line-specific variations were also observed, with HepG2 displaying more uniquely expressed genes expression levels (fold changes) shared conditions. Validation qPCR confirmed key within time points. These findings provide insights into context-specific aspects HSR, contributing comprehensive understanding mechanisms mammalian cells.

Language: Английский

Citations

0