Lasmiditan ameliorates serotonergic itch in mice: Possible involvement of 5-HT1F receptors.

Previously, some allergic conditions involving pruritus have been linked to migraine, raising the possibility that migraine and itching may be governed by similar underlying mechanisms. We aimed to investigate the efficacy of Lasmiditan, a highly selective agonist of the 5-hydroxytryptamine 1F (5-HT1F) receptor and a recently approved medication for the treatment of migraine headaches, in ameliorating serotonergic itching. Forty animals were employed in the present study (n = 40). Eight animals were randomly assigned to each of the following study groups (n = 8, in each group): (1) "Normal Saline": This group was given intradermal injections of normal saline (2) "5-HT": The animals were injected with intradermal 5-HT, which was used to induce itching. (3) "Lasmiditan 0.3", "Lasmiditan 1", and "Lasmiditan 3" groups: injected with 5-HT as well as intraperitoneal Lasmiditan at different dose levels (0.3, 1, and 3 mg/kg, respectively). Scratching behavior was recorded for 60 min, and the skin tissue of three mice was sampled at the end of the behavioral experiment to assess the levels of TLR-4, IL-31, 5-HT1F receptor, CGRP & TRPV4. In the present study, we found that Lasmiditan when administered at 1 mg/kg effectively reduced serotonin-induced itching compared to the "5-HT" group (P < 0.0001). Following the administration of Lasmiditan (1 mg/kg), the expression levels of the 5-HT1F receptor significantly increased (P < 0.01). Further, the levels of TLR-4, IL-31, CGRP & TRPV4 were substantially reduced upon the administration of Lasmiditan (1 mg/kg). We found that Lasmiditan is effective in reducing serotonergic itch in mice through its interaction with the 5-HT1F receptor in the skin tissue of mice.

Sumatriptan mitigates bleomycin-induced lung fibrosis in male rats: Involvement of inflammation, oxidative stress and α-SMA.

INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) is a fibrotic lung condition that produces symptoms including coughing which may cause by excessive accumulation of scar tissue inflammatory and oxidative stress exacerbation. Sumatriptan, utilized for migraine treatment as a selective 5-HT1B/1D receptor agonist, has demonstrated significant anti-inflammatory and antioxidant properties in multiple preclinical investigations. Operating primarily on serotonin receptors, sumatriptan leverages the diverse physiological functions of serotonin, playing a pivotal role in regulating both inflammation and oxidative stress which is particularly relevant in the context of IPF. MATERIALS & METHODS: Thirty-five male Wistar rats were divided to five group, including: Sham (without IPF induction), control (BLM 5 mg/kg, intraperitoneally), and three fibrosis group with sumatriptan (0.5, 1, and 3 mg/kg, i.p. for 2 weeks) administration. IPF was induced by injection of BLM (single dose, 5 mg/kg intratracheally). Lung tissues were separated for measurement of myeloperoxidase (MPO) as an oxidative stress hallmark, and tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-ß), and transforming growth factor-ß (TGF-ß) as inflammatory markers as well as alpha smooth muscle actin (α-SMA). Also, for histological investigations, tissue damages were assessed by Hematoxylin-eosin (H&E) and Masson's trichrome staining method. RESULTS: BLM-induced fibrosis could increase α-SMA, MPO, TNF-α, IL-1ß, and TGF-ß, while treatment with sumatriptan has reversed the α-SMA, MPO, and IL-1ß levels. Moreover, the results of H&E and Masson's trichrome staining indicated that sumatriptan (1 and 3 mg/kg) reduced tissue damages, alveolar wall thickness, collagen accumulation, and pulmonary fibrosis induced by BLM. CONCLUSION: According to the data achieved from this study, Sumatriptan appears to have therapeutic benefits in IPF, possibly via reducing α-SMA as well as inflammation and the toxicity caused by oxidative stress.

The emerging roles of long non-coding RNA (lncRNA) H19 in gynecologic cancers.

Long non-coding RNA (lncRNA) H19 has gained significant recognition as a pivotal contributor to the initiation and advancement of gynecologic cancers, encompassing ovarian, endometrial, cervical, and breast cancers. H19 exhibits a complex array of mechanisms, demonstrating dualistic effects on tumorigenesis as it can function as both an oncogene and a tumor suppressor, contingent upon the specific context and type of cancer being investigated. In ovarian cancer, H19 promotes tumor growth, metastasis, and chemoresistance through modulation of key signaling pathways and interaction with microRNAs. Conversely, in endometrial cancer, H19 acts as a tumor suppressor by inhibiting proliferation, inducing apoptosis, and regulating epithelial-mesenchymal transition. Additionally, H19 has been implicated in cervical and breast cancers, where it influences cell proliferation, invasion, and immune evasion. Moreover, H19 has potential as a diagnostic and prognostic biomarker for gynecologic cancers, with its expression levels correlating with clinical parameters and patient outcomes. Understanding the functional roles of H19 in gynecologic cancers is crucial for the development of targeted therapeutic strategies and personalized treatment approaches. Further investigation into the intricate molecular mechanisms underlying H19's involvement in gynecologic malignancies is warranted to fully unravel its therapeutic potential and clinical implications. This review aims to elucidate the functional roles of H19 in various gynecologic malignancies.