Hypoxia is associated with poor prognosis and therapeutic resistance in cancer patients. Accumulating evidence has shown that microRNA (miRNA) plays an important role in the acquired drug resistance in colorectal carcinoma (CRC). However, the role of miRNA in hypoxia-induced CRC drug resistance remains to be elucidated. Here, we identified a hypoxia-triggered feedback loop that involves hypoxia-inducible transcription factor 1α (HIF-1α)-mediated repression of miR-338-5p and confers drug resistance in CRC. In this study, the unbiased miRNA array screening revealed that miR-338-5p is downregulated in both hypoxic CRC cell lines tested. Repression of miR-338-5p was required for hypoxia-induced CRC drug resistance. Furthermore, we identified interleukin-6 (IL-6), which mediates STAT3/Bcl2 activation under hypoxic conditions, as a direct miR-338-5p target. The resulting HIF-1α/miR-338-5p/IL-6 feedback loop was necessary for drug resistance in colon cancer cell lines. Using CRC patient samples, we found miR-338-5p has a negative correlation with HIF-1α and IL-6. Finally, in a xenograft model, overexpressing miR-338-5p in CRC cells and HIF-1α inhibitor PX-478 were able to enhance the sensitivity of CRC to oxaliplatin (OXA) via suppressing the HIF-1α/miR-338-5p/IL-6 feedback loop in vivo. Taken together, our results uncovered an HIF-1α/miR-338-5p/IL-6 feedback circuit that is critical in hypoxia-mediated drug resistance in CRC; targeting each member of this feedback loop could potentially reverse hypoxia-induced drug resistance in CRC.
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http://dx.doi.org/10.1016/j.ymthe.2019.05.017 | DOI Listing |
Arch Bronconeumol
December 2024
Pulmonology Service, Cruces University Hospital (OSI EEC), Barakaldo, Spain; BioBizkaia Health Research Institute, Spain.
The Spanish Society of Pneumology and Thoracic Surgery (SEPAR) and the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) have developed together Clinical Practice Guidelines (GPC) on the management of people affected by tuberculosis (TB) resistant to drugs with activity against Mycobacterium tuberculosis. These clinical practice guidelines include the latest updates of the SEPAR regulations for the diagnosis and treatment of drug-resistant TB from 2017 and 2020 as the starting point. The methodology included asking relevant clinical questions based on PICO methodology, a literature search focusing on each question, and a systematic and comprehensive evaluation of the evidence, with a summary of this evidence for each question.
View Article and Find Full Text PDFEmerg Microbes Infect
January 2025
Department of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Shenzhen Third People's Hospital, Shenzhen, Guangdong Province 518112, China.
() commonly induces refractory infection due to its multidrug-resistant nature. To date, there have been no reports on the application of phage treatment for infection. This study was conducted to explore the feasibility of phage application in treating refractory infection by collaborating with a 59-year-old male patient with a pulmonary infection of multidrug-resistant Our experiments included three domains: ) selection of the appropriate phage, ) verification of the efficacy and safety of the selected phage, ) confirmation of phage-bacteria interactions.
View Article and Find Full Text PDFJ Antimicrob Chemother
January 2025
Research Laboratory, Botswana Harvard Health Partnership, Gaborone, Botswana.
Objectives: We assessed HIV-1 drug resistance profiles among people living with HIV (PLWH) with detectable viral load (VL) and on dolutegravir-based antiretroviral therapy (ART) in Botswana.
Methods: The study utilised available 100 residual HIV-1 VL samples from unique PLWH in Francistown who had viraemia at-least 6 months after initiating ART in Botswana's national ART program from November 2023 to January 2024. Viraemia was categorized as low-level viraemia (LLV) (VL: 200-999 copies/mL) or virologic failure (VF) (VL ≥1000 copies/mL).
ACS Nano
January 2025
State Key Laboratory of Fine Chemicals, College of Materials Science and Engineering, Shenzhen University, Shenzhen 518055, China.
Biofilm-induced chronic bacterial infections represent a significant challenge in modern medicine due to their resistance to conventional antibiotic treatments. Although photodynamic therapy (PDT) has emerged as a promising antibiotic-free antibacterial strategy, the hypoxic condition within biofilms and the lack of an effective local drug delivery system have limited the clinical effectiveness of photosensitizer (PS) agents. Herein, we propose a type of charge regulation-enhanced type I PS-loaded hydrogel dressing for treating biofilm infection.
View Article and Find Full Text PDFN4-acetylcytidine (ac4C) modification is a crucial RNA modification widely present in eukaryotic RNA. Previous studies have demonstrated that ac4C plays a pivotal role in viral infections. Despite numerous studies highlighting the strong correlation between ac4C modification and cancer progression, its detailed roles and molecular mechanisms in normal physiological processes and cancer progression remain incompletely understood.
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