Role of TREK-1 in Health and Disease, Focus on the Central Nervous System

Conclusion and Perspectives Since their cloning 20 years ago, the physiological importance of TREK-1 channels has continued to grow (Figure 3). Today, TREK-1 channels have been shown to be important and their presence is essential in a number of physiopathological processes. Their involvement in these different processes demonstrate the necessity to design pharmacological modulators, activators or inhibitors, of these channels to correct any TREK-1-related dysfunctions. Despites a number of studies and many molecule screenings, only few putative new drugs were identified. The activators belonging to the ML and BL series show interesting results. However, they display lower affinities (in the micromolar range) and they are not specific for TREK-1 channels as they open other K2P channels. TREK-1 openers are needed in pathologies such as ischemia, epilepsy and pain. The challenge is to improve their affinity, specificity and ability to cross the blood-brain barrier. The new ML and BL series of TREK- activators have not yet been tested in pathologies such epilepsy and ischemia. It would be interesting to investigate any neuroprotection effects of these molecules in rodent models of epilepsy or ischemia. In the same time, their specificity should be improved to avoid any off-target effects resulting from modulating other K2P channels. As inhibitors, the most promising molecules are spadin and its analogs. These peptides are very specific in the K2P family and display very high ...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research

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Publication date: Available online 17 July 2019Source: Journal of Integrative MedicineAuthor(s): Pierre Watcho, Ismaelle Rosine Mpeck, Patrick Brice Defo Deeh, Modeste W.eu-Nya, Esther Ngadjui, Georges Romeo Fozin Bonsou, Pierre Kamtchouing, Albert KamanyiAbstractObjectiveCyclophosphamide (CP) is commonly used to treat some cancers, but its clinical efficacy is also linked with testicular toxicity. We investigated the effects of aqueous extract (AE) and methanolic extract (ME) of Helichrysum odoratissimum for reducing CP-induced reproductive toxicity in male rats.MethodsIn addition to a normal control (group 1), drugs or v...
Source: Journal of Integrative Medicine - Category: Complementary Medicine Source Type: research
This study used Oswestry Disability Index (ODI)-self-comparison and showed that acupuncture treatments for lumber disc herniation and sciatica demonstrated significant improvement in long term clinical outcomes. A total of 112 lumbar disc herniation and sciatica cases were treated with electric acupuncture for pain relief and function improvement from July 1998 to December 2006.ResultsAll the 112 cases filled out the ODI forms prior to receiving treatment. Among the 112 patients, 23 of them did not finish the 6-week treatments. 89 cases were evaluated with ODI after 6-week acupuncture treatments. Of those 89 cases, 67 case...
Source: World Journal of Acupuncture Moxibustion - Category: Complementary Medicine Source Type: research
ConclusionsThe therapeutic effect of acupuncture and moxibustion by soothing liver and regulating mind can obviously improve the quality of life of depression elders.
Source: World Journal of Acupuncture Moxibustion - Category: Complementary Medicine Source Type: research
Conclusion: Experiences of being sexually harassed correlate among adolescents with high social anxiety but also with high self-esteem. Sexual harassment among adolescents may partly be explained as inept ways of showing interest, but it may nevertheless have detrimental effects on the well-being of the those subjected to it. PMID: 31311376 [PubMed - as supplied by publisher]
Source: Nordic Journal of Psychiatry - Category: Psychiatry Tags: Nord J Psychiatry Source Type: research
Publication date: Available online 17 July 2019Source: Clinical Lymphoma Myeloma and LeukemiaAuthor(s): Fernando Cabanillas, Noridza Rivera, Mirelis Acosta, Wandaly Pardo, Pedro Solivan, Caroline Rivera, Idalia LiboyAbstractBackgroundOur objective was to evaluate the impact of lenalidomide in patients with aggressive lymphoma who attained
Source: Clinical Lymphoma Myeloma and Leukemia - Category: Cancer & Oncology Source Type: research
We report a case of a patient affected by AC progressed to available standard treatments who received off-label treatment with sunitinib, a well-known multitarget tyrosine-kinase inhibitor with marked antiangiogenic activity, used routinely for the treatment of GEP-NETs. During treatment, the patient required the administration of an alternative schedule to improve tolerability, with benefit, and achieved a partial response according to the RECIST criteria, which is unusual in NETs. We critically reviewed available data supporting the use of somatostatin analogs, chemotherapy, and target therapies (everolimus and sunitinib...
Source: Anti-Cancer Drugs - Category: Cancer & Oncology Tags: Review Articles Source Type: research
Colorectal cancer (CRC) remains a leading cause of cancer-related morbidity and mortality worldwide. Although targeted therapy in combination with chemotherapy in CRC prolongs the overall survival of patients with metastatic disease, acquired resistance and relapse hinder their clinical benefits. Moreover, patients with some specific genetic profile are unlikely to benefit from targeted therapy, suggesting the need for safe and effective treatment strategies. Retinoids, comprising of natural and synthetic analogs, are a class of chemical compounds that regulate cellular proliferation, differentiation, and cell death. Retin...
Source: Anti-Cancer Drugs - Category: Cancer & Oncology Tags: Review Articles Source Type: research
This study clarifies that sevoflurane inhibits proliferation, invasion, and migration, and promotes apoptosis in glioma cells. These effects are regulated by IGF-1, an upstream gene of the PI3K/AKT signaling pathway. These findings may be significant for the selection of anesthetic agents in glioma surgery to improve the prognosis of patients.
Source: Anti-Cancer Drugs - Category: Cancer & Oncology Tags: Preclinical Reports Source Type: research
In this study, we demonstrated that EZH2 induced sorafenib resistance of HCC cells in vitro. Mechanistically, EZH2 was a potent regulator of insulin-like growth factor 1 receptor (IGF1R) and EZH2-modulated IGF1R expression by directly transcriptionally repressing a set of microRNAs (miRNAs) including miR-101, miR-122, miR-125b, and miR-139. These miRNAs were required for EZH2-mediated sorafenib resistance by promoting IGF1R expression. Surprisingly, IGF1R inhibitors significantly reversed EZH2-induced sorafenib resistance. Collectively, we proposed a novel model for an EZH2 – miRNAs – IGF1R regulatory axis, whi...
Source: Anti-Cancer Drugs - Category: Cancer & Oncology Tags: Preclinical Reports Source Type: research
Pyrvinium tosylate (PT) is an anthelminthic drug that has recently been shown to suppress various human cancers. However, whether PT is effective in nasopharyngeal carcinoma (NPC) has not been determined to date. In this work, we show the selective efficacy of PT in NPC while sparing normal nasopharyngeal epithelial cells, and its ability to increase chemosensitivity. We show that PT at 100 and 500 nmol/l significantly inhibits growth and induces apoptosis in several NPC cell lines without affecting normal nasopharyngeal epithelial cells. Using cell culture and xenograft mouse models, PT markedly enhances cisplatin’s...
Source: Anti-Cancer Drugs - Category: Cancer & Oncology Tags: Preclinical Reports Source Type: research
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