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Purpose: This paper reports a systematic review and meta-analysis protocol that will be used to evaluate the efficacy and safety of pembrolizumab, alone or combined with bevacizumab and other therapies, in adult women with cervical carcinoma from stage IB2 onwards., Methods: The protocol follows PRISMA-P recommendations and was registered on PROSPERO (CRD42024531233). The search will be conducted without restrictions on language and year of publication in the following databases: Pubmed, Embase, Scopus, Web of Science, Cancerlit, The World Health Organization (WHO), International Clinical Trials Registry Platform (ICTRP) and Clinical Trials Registry Platform. Grey literature will be searched using the following sources: Clinicaltrials.gov, Google Scholar and Opengrey. Manual search will be carried out for the reference lists of eligible studies. The studies will be selected independently by two reviewers and all completed or ongoing randomized clinical trials that evaluated the efficacy and safety of pembrolizumab, used alone or combined with chemotherapy, radiotherapy, bevacizumab or surgery, in adult women diagnosed with cervical cancer, will be included. The data extraction will include population characteristics, type of treatment and main outcomes of studies. The methodological quality of the studies will be assessed using the Cochrane Risk of Bias 2.0. The certainty of the evidence will be rated using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE)., Conclusions: The findings will be presented in narrative summary tables and a quantitative synthesis will be conducted using the 'meta' package of R software, version 4.3.1. This future systematic review may contribute with quality evidence for clinical decision-making on the use of pembrolizumab in women with cervical cancer., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Dantas et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Lippia alba is popularly known as lemon balm, with its essential oil (EO) cited for displaying antimicrobial, sedative, and vasorelaxant effects. Yet, its action on isolated human vessels has not been described in the literature. Thus, we evaluated the vasorelaxant effect of essential oil of L. alba (EOLa) on human umbilical arteries (HUA) isolated in organ baths. HUA rings were isolated, subjected to contractions induced by potassium chloride (KCl), serotonin (5-HT), or histamine (HIST) to record the isometric tension, and then treated with EOLa (30-1000 µg/mL). The EOLa showed a more prominent inhibitory effect on the pharmacomechanical coupling contraction via HIST with an EC 50 value of 277.1 ± 8.5 µg/mL and maximum relaxant effect at 600 µg/mL. The addition of tetraethylammonium (TEA) or 4-aminopyridine (4-AP) in HUA preparations did not inhibit EOLa total relaxant effect at 1000 µg/mL. In the presence of gliblenclamide (GLI), the oil relaxed the HUA rings by 90.8% at maximum concentration. The EOLa was also investigated for its effects on voltage-operated calcium channels (VOCCs), where the HUA preincubation with this oil at 1000 μg/mL inhibited BaCl 2 (0.1-30 mM)-induced contractions. This study demonstrates for the first time that EOla has a vasorelaxant effect on HUA and its particular blockade of VOCCs.

Eugenol (EUG) is a phenylpropanoid widely used in the food and cosmetic industries. It is commonly referred to in the literature by its biological activities such as antioxidant, anti-inflammatory, antimicrobial, and relaxing in organs of laboratory animals, especially in rodent vessels. However, its vasorelaxant potential in human tissue, has not been investigated. Thus, this study characterizes the vasodilatory effect of EUG in the human umbilical artery (HUA). HUAs were isolated, cleaned, sectioned (3-4 mm) and placed in an organ bath (10 mL Krebs Henseleit, 37 °C; and carbogenic mixture). EUG (100-1400 μM), obtained total relaxation of electromechanical contractions induced by KCl (60 mM), and pharmacomechanical contractions (30-1200 μM), induced by serotonin (10 μM) and by histamine (10 μM), showing statistically significant concentrations: 600 μM, 400 μM and 200 μM, and EC 50 values: 759.8 ± 6.5 μM, 229.9 ± 7.9 and 279.0 ± 3.4 μM, respectively. EUG (1200 and 1400 μM) prevented the contraction promoted by BaCl 2 (0.1-30 mM), similar to the effects of nifedipine (10 μM), sugesting the involvement of EUG in blocking VOCCs. In the presence of tetraethylammonium (10 μM), EUG (30-1200 μM) did not produce a total relaxation (88.6%), suggesting that an alternative pathway where potassium channels, may partially mediate EUG effect. In the presence of 4-aminopyridine (1 mM), glibenclamide (10 μM), and tetraethylammonium (1 mM), EUG relaxed HUAs 100%, although the pharmacological potency was statistically altered, demonstrating the participation of K + channels (Kv, KATP, BKCa). Our data indicates that EUG has a vasorelaxant effect on HUAs, had a greater pharmacological potency in the serotoninergic pathway, showing effective participation of VOCCs and a partial modulation of K + channels. These data suggest new possibilities for the use of EUG in human vascular dysfunctions, such as preeclampsia. More studies are necessary to confirm the safety and effectivity in future treatments., (Copyright © 2022 Elsevier B.V. All rights reserved.)