Millions of new cases of cancer are diagnosed worldwide each year, making it a serious public health concern. Developments in customized therapy and early detection have significantly enhanced treatment for and results from cancer. Therefore, it is important to investigate new molecular biomarkers. In this study, we created an efficient transient receptor potential melastatin (TRPM) family members-related TRPM-Score for 17 solid tumors. CCNE1, produced from TRPM-Score, was found to be an exceptional biomarker through several sophisticated machine learning and deep learning computational techniques. TRPM-Score and CCNE1 immunotherapeutic prediction, immunological characteristics, and predictive value were thoroughly assessed. In most cancer types, CCNE1 was a substantially dangerous marker. Additional in vitro tests validated CCNE1's immunomodulatory properties, demonstrating that silencing impeded macrophage movement and decreased PD-L1 expression. Additionally, CCNE1 may accurately predict responses to cancer immunotherapy. These findings indicate that the TRPM family-particularly CCNE1, which is associated with TRPM-is a significant player in the pan-cancer domain and can be utilized as a therapeutic target and prognostic biomarkers, especially in immuno-oncology. The thorough characterization of the TRPM family and the discovery of CCNE1 as a crucial downstream effector mark important developments in our comprehension of pan-cancer biology.
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http://dx.doi.org/10.1186/s12943-024-02169-7 | DOI Listing |
Sci Adv
January 2025
Department of Neuroscience, Helen Wills Neuroscience Institute, Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, CA 94720, USA.
Homeostatic sleep regulation is essential for optimizing the amount and timing of sleep for its revitalizing function, but the mechanism underlying sleep homeostasis remains poorly understood. Here, we show that optogenetic activation of locus coeruleus (LC) noradrenergic neurons immediately increased sleep propensity following a transient wakefulness, contrasting with many other arousal-promoting neurons whose activation induces sustained wakefulness. Fiber photometry showed that repeated optogenetic or sensory stimulation caused a rapid reduction of calcium activity in LC neurons and steep declines in noradrenaline/norepinephrine (NE) release in both the LC and medial prefrontal cortex (mPFC).
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2025
Department of Neurology, the Second Affiliated Hospital, Neuroscience Research Center, Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710000, China.
Neurotransmitters and neuromodulators can be released via either action potential (AP)-evoked transient or AP-independent continuous neurotransmission. The elevated AP-evoked neurotransmission in the primary sensory neurons plays crucial roles in hyperalgesia. However, whether and how the AP-independent continuous neurotransmission contributes to hyperalgesia remains largely unknown.
View Article and Find Full Text PDFAm J Transl Res
December 2024
Department of Otolaryngology-Head and Neck Surgery, Jinhua People's Hospital Jinhua 321000, Zhejiang, China.
Objective: This study aimed to investigate the effects of cinnamaldehyde (CA) intervention on transient receptor potential melastatin 8 (TRPM8) expression in human nasal epithelial cells (HNECs) and mouse models of chronic rhinosinusitis (CRS) and determine the alleviating effects of CA on CRS.
Methods: HNECs were treated with CA, and the protein levels and mRNA expression of pro-inflammatory cytokines, namely, interleukin-25 (IL-25), IL-33, and thymic stromal lymphopoietin (TSLP), were measured by enzyme-linked immunosorbent assay and real-time reverse-transcription polymerase chain reaction (RT-PCR). TRPM8 expression levels were examined by RT-PCR and western blot.
Cureus
January 2025
Research, Clarity Science LLC, Narragansett, USA.
The recent identification of Piezo ion channels demonstrating a mechano-sensitive impact on neurons revealed distinct Piezo-1 and 2 types. While Piezo-1 predominates in neurons linked to non-sensory stimulation, such as pressure in blood vessels, Piezo-2 predominates in neurons linked to sensory stimulation, such as touch. Piezo-1 and 2 have a major bidirectional impact on transient receptor potential (TRP) ion channels, and TRPs also impact neurotransmitter release.
View Article and Find Full Text PDFActa Physiol (Oxf)
February 2025
Deptrtment of Anesthesiology, University of Nebraska Medical Center, Omaha, Nebraska, USA.
Aim: Tissue clearance is a rapidly evolving technology that allows for the three-dimensional imaging of intact biological tissues. Preexisting tissue-clearing techniques, such as Passive Clarity Technique (PACT) and Clear Unobstructed Brain Imaging Cocktails and Computational Analysis (CUBIC), clear tissues adequately but have distinct disadvantages, such as taking extensive time to clear tissues and degradation of endogenous tissue fluorescence. We developed a new tissue-clearing technique combining PACT and CUBIC protocols to map the neural lineages expressing the transient receptor potential vanilloid type 1 (TRPV1) receptor.
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