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1.
Int J Mol Sci ; 25(11)2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38892251

RESUMO

MicroRNAs (miRNAs), particularly miR-16 and miR-21, play a crucial role in multiple myeloma (MM) pathogenesis by regulating gene expression. This study evaluated the prognostic significance of circulating miR-16 and miR-21 expression levels in 48 patients with MM at diagnosis treated with lenalidomide-dexamethasone (LD) compared with 15 healthy individuals (HI). All patients were treated with LD, 13 at first line and 35 at relapse, of whom 21 were tested twice at diagnosis and before LD initiation. The results revealed significantly lower levels of miR-16 and miR-21 in patients than in HIs, both at diagnosis and relapse, with decreased miR-16 levels at diagnosis, indicating improved overall survival (OS) (p value 0.024). Furthermore, miR-16 and miR-21 levels were associated with disease markers, while both correlated with the depth of response and mir-16 with sustained response to LD treatment. Ratios of both miR-16 and miR-21 expression levels (prior to LD treatment/diagnosis) below two predicted a shorter time to response (p = 0.027) and a longer time to next treatment (p = 0.042), respectively. These findings suggested a prognostic value for serum miR-16 and miR-21 levels in MM, as their expression levels correlated with disease variables and treatment outcomes.


Assuntos
Lenalidomida , MicroRNAs , Mieloma Múltiplo , Talidomida , Humanos , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/genética , Mieloma Múltiplo/sangue , Mieloma Múltiplo/mortalidade , MicroRNAs/sangue , MicroRNAs/genética , Lenalidomida/uso terapêutico , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Prognóstico , Talidomida/análogos & derivados , Talidomida/uso terapêutico , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Dexametasona/uso terapêutico , Idoso de 80 Anos ou mais , Adulto , Regulação Neoplásica da Expressão Gênica , MicroRNA Circulante/sangue , Resultado do Tratamento
2.
Noncoding RNA ; 10(3)2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38921830

RESUMO

Hypertension is a chronic, multifactorial disease, leading to high cardiovascular morbidity and mortality globally. Despite the advantages of pharmaceutical treatments, natural products have gained scientific interest due to their emerging phytotherapeutic properties. Chios mastic is a natural Greek product, consisting of bioactive compounds which modify microRNAs' (small, expression-regulating molecules) expression. In this study, we investigated the antihypertensive properties of Chios mastic through the assessment of miR-21 levels. Herein, plasma samples of 57 individuals with hypertension, recruited for the purposes of the HYPER-MASTIC study, were analyzed. This was a clinical trial with Chios mastic supplements in which the patients were divided into groups receiving high and low mastic doses and placebo supplements, respectively. miR-21 was significantly upregulated in patients compared to normotensive individuals. Mean changes in miR-21 levels were statistically significant, after adjusting for sex and age, between the placebo and low-dose group and between the low- and high-dose group. Post-intervention miR-21 levels were positively associated with night-time systolic blood pressure, pulse pressure, and central systolic mean arterial pressure and negatively associated with night-time pulse wave velocity in the low-dose group. Our findings suggest a potential implication of miR-21 in the association of Chios mastic with night-time blood pressure measurements.

3.
Nutrients ; 16(13)2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38999899

RESUMO

Background: Hypertension poses a significant global health burden and is associated with cardiovascular morbidity. Chios mastic gum (CMG), derived from Pistacia lentiscus var. Chia, shows potential as a phytotherapeutic agent, due to its multifaceted beneficial effects. However, its anti-hypertensive effects and vascular, circulatory, and renal-related dysfunction, have not been thoroughly investigated. Herein, we aimed to explore the antihypertensive potential of CMG, focusing on vascular and renal endothelium, in vivo. Methods: Two models of hypertension in male rats, induced by Angiotensin II and Deoxycorticosterone acetate (DOCA)-high-salt administration, were utilized. CMG was administered at 220 mg/kg daily for four weeks after hypertension onset and blood pressure was measured non-invasively. Whole blood RNA sequencing, metabolomics, real-time PCR, and Western blot analyses of kidney and aorta tissues were additionally performed. Results: CMG significantly lowered systolic, diastolic, and mean blood pressure in both models. RNA sequencing revealed that CMG modulated immunity in the Angiotensin II model and metabolism in the DOCA-HS model. CMG downregulated genes related to oxidative stress and endothelial dysfunction and upregulated endothelial markers such as Vegfa. Metabolomic analysis indicated improved endothelial homeostasis via lysophosphatidylinositol upregulation. Conclusions: CMG emerges as a potent natural antihypertensive therapy, demonstrating beneficial effects on blood pressure and renal endothelial function.


Assuntos
Anti-Hipertensivos , Pressão Sanguínea , Hipertensão , Pistacia , Animais , Pistacia/química , Masculino , Hipertensão/tratamento farmacológico , Anti-Hipertensivos/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Ratos , Rim/efeitos dos fármacos , Rim/metabolismo , Resina Mástique , Modelos Animais de Doenças , Angiotensina II , Ratos Sprague-Dawley , Acetato de Desoxicorticosterona , Estresse Oxidativo/efeitos dos fármacos , Endotélio Vascular/efeitos dos fármacos , Extratos Vegetais/farmacologia
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