Purpose Heart rate reduction (HR) is a cornerstone in heart failure therapy as it improves patient outcomes. The aim of this study is to evaluate short-term effect of ivabradine on NT-Pro BNP and neopterin in heart failure patients and assess the association between HR and these biomarkers. Methods Sixty patients on standard heart failure therapy were randomly allocated into ivabradine group (n = 30) and non-ivabradine group (n = 30). Ivabradine 5 mg twice daily was given for 3 months. Lipid profile and kidney functions were performed and blood samples for NT-Pro BNP and neopterin were analysed at baseline and after 3 months of intervention in both groups. Results There was a significant improvement in NYHA class in ivabradine group (p < 0.001). Ejection fraction was improved in ivabradine and non-ivabradine groups after intervention (p < 0.001), with a greater improvement in ivabradine group (p = 0.026). Heart rate was reduced in ivabradine group (p < 0.001) and non-ivabradine group (p < 0.001) yet greater reduction was seen in ivabradine group (p < 0.001). Serum creatinine and blood urea nitrogen were reduced in ivabradine group (Scr: p = 0.001, BUN: p = 0.001). NT-Pro BNP and neopterin levels significantly decreased in ivabradine group (NT-Pro BNP: p < 0.001, neopterin p < 0.001). Significant positive correlation was found between HR and biomarker levels after intervention (NT-Pro BNP: r = 0.475, p < 0.001, neopterin: r = 0.384, p = 0.002). Conclusion Ivabradine therapy reduced levels of both biomarkers which correlated well with HR. Biomarker levels might provide a tool for assessing ivabradine effectiveness in HF. Trial registration Date: June 26, 2020. Identifier: NCT04448899. Link: Ivabradine in Patients with Congestive Heart Failure—Full Text View—ClinicalTrials.gov.
Breast cancer (BC) is considered one of the most prevalent malignancies impacting women worldwide, constituting 15% of all new cancer cases. It is classified according to its molecular targets into three subtypes; HR+/ERBB2‐, ERBB2+/HR+, or HR‐ and triple‐negative breast cancer (TNBC). TNBC is considered aggressive cancer with bad prognosis and poor clinical outcomes. It lacks estrogen, progesterone, and ERBB2 receptors rendering its treatment more challenging. Owing to its unresponsiveness to hormonal therapy, quick tumor growth, and the high probability to have spread at the time of discovery, it is more likely to recur following therapy. Proteolysis Targeting Chimeric molecules (PROTACs) are hetero‐bifunctional molecules that are able to hijack the ubiquitin‐proteasome system, a major physiological proteolytic mechanism. This leads to ubiquitination through endogenous E3 ligases and subsequent degradation through 26‐S proteasome. Since its discovery in 2001, PROTACs have been considered an important therapeutic modality due to their ability to target and degrade undruggable proteins. In vitro studies have been conducted to investigate the possibility of using PROTACs as a therapeutic modality in TNBC. Data available propose great potential of PROTACs technology as a major candidate in TNBC management. Further in vitro and in vivo clinical trials are required to establish a definitive decision. In this review, we aim to give a brief overview of TNBC and PROTACs and highlight the rationale behind using PROTACs as a therapeutic modality in patients with TNBC.
Inflammation has a major role in the pathogenesis of heart failure (HF). It triggers a cascade that leads to the release of pro-inflammatory cytokines which in turn cause cardiac hypertrophy, fibrosis, apoptosis, negative inotorpy and leukocyte recruitment which worsen the condition. Neopterin is an inflammatory biomarker which is released as a response to macrophage activation. Levels of neopterin are elevated in conditions which has an immunological component such as autoimmune disease, viral and bacterial infections and malignancy. Neopterin levels were found to be elevated in patients with HF. This is due to the fact that inflammation takes place during the development of the condition. Studies demonstrated that neopterin can be used as a biomarker for diagnosing HF, determining severity of the disease and monitoring its progression. Neopterin levels were higher in patients with New York Heart Association classification (NYHA) III–IV more than class I–II. Moreover, neopterin levels correlated well with morbidity and mortality. It has been suggested that neopterin be monitored levels to determine effectiveness of HF treatment options. Graphical abstract
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