Combined chemotherapy is a treatment method based on the simultaneous use of two or more therapeutic agents; it is frequently necessary to produce a more effective treatment for cancer patients. Such combined treatments often improve the outcomes over that of the monotherapy approach, as the drugs synergistically target critical cell signaling pathways or work independently at different oncostatic sites. A better prognosis has been reported in patients treated with combination therapy than in patients treated with single drug chemotherapy. In recent decades, 5-fluorouracil (5-FU) has become one of the most widely used chemotherapy agents in cancer treatment. This medication, which is soluble in water, is used as the first line of anti-neoplastic agent in the treatment of several cancer types including breast, head and neck, stomach and colon cancer. Within the last three decades, many studies have investigated melatonin as an anti-cancer agent; this molecule exhibits various functions in controlling the behavior of cancer cells, such as inhibiting cell growth, inducing apoptosis, and inhibiting invasion. The aim of this review is to comprehensively evaluate the role of melatonin as a complementary agent with 5-FU-based chemotherapy for cancers. Additionally, we identify the potential common signaling pathways by which melatonin and 5-FU interact to enhance the efficacy of the combined therapy. Graphic abstract

Mesenchymal stem cells (MSCs), as adult multipotent cells, possess considerable regenerative and anti-neoplastic effects, from inducing apoptosis in the cancer cells to reducing multidrug resistance that bring them up as an appropriate alternative for cancer treatment. These cells can alter the behavior of cancer cells, the condition of the tumor microenvironment, and the activity of immune cells that result in tumor regression. It has been observed that during inflammatory conditions, a well-known feature of the tumor microenvironment, the MSCs produce and release some molecules called “antimicrobial peptides (AMPs)” with demonstrated anti-neoplastic effects. These peptides have remarkable targeted anticancer effects by attaching to the negatively charged membrane of neoplastic cells, disrupting the membrane, and interfering with intracellular pathways. Therefore, AMPs could be considered as a part of the wide-ranging anti-neoplastic effects of MSCs. This review focuses on the possible anti-neoplastic effects of MSCs-derived AMPs and their mechanisms. It also discusses preconditioning approaches and using exosomes to enhance AMP production and delivery from MSCs to cancer cells. Besides, the clinical administration of MSCs-derived AMPs, along with their challenges in clinical practice, were debated.

Background: Machine learning (ML) has shown promising results in all fields of medicine, including preventive cardiology. Hypertensive patients are at higher risk of mortality after coronary artery bypass graft (CABG) surgery; thus, we aimed to design and evaluate five ML models to predict 1-year mortality among hypertensive patients who underwent CABG.Hyothesis: ML algorithms can significantly improve mortality prediction after CABG.Methods: Tehran Heart Center's CABG data registry was used to extract several baseline and peri-procedural characteristics and mortality data. The best features were chosen using random forest (RF) feature selection algorithm. Five ML models were developed to predict 1-year mortality: logistic regression (LR), RF, artificial neural network (ANN), extreme gradient boosting (XGB), and naïve Bayes (NB). The area under the curve (AUC), sensitivity, and specificity were used to evaluate the models.Results: Among the 8,493 hypertensive patients who underwent CABG (mean age of 68.27 ± 9.27 years), 303 died in the first year. Eleven features were selected as the best predictors, among which total ventilation hours and ejection fraction were the leading ones. LR showed the best prediction ability with an AUC of 0.82, while the least AUC was for the NB model (0.79). Among the subgroups, the highest AUC for LR model was for two age range groups (50-59 and 80-89 years), overweight, diabetic, and smoker subgroups of hypertensive patients.Conclusions: All ML models had excellent performance in predicting 1-year mortality among CABG hypertension patients, while LR was the best regarding AUC. These

BackgroundThere is no concise evidence or clinical guidelines regarding the incidence of sinus node dysfunction (SND) and permanent pacemaker (PPM) implantation following cardiac surgeries and their management approaches.ObjectiveWe aim to systematically review current evidence on the prevalence of SND, PPM implantation concerning it, and its risk factors in patients undergoing cardiac surgery.MethodFour electronic databases (Cochrane Library, Medline, SCOPUS, and Web of Science) were systematically searched for articles regarding SND after cardiovascular surgeries and reviewed by two independent researchers, and a third review in case of discrepancies. Using the random-effects model, a proportion meta-analysis was performed on data regarding PPM implantation. Subgroup analysis was performed for different interventions, and the possible effect of different covariates was evaluated using meta-regression.ResultsFrom the initial 2012 unique records, 87 were included in the study, and results were extracted. Pooled data from 38,519 patients indicated that the overall prevalence of PPM implantation due to SND after cardiac surgery was 2.87% (95% CI [2.09; 3.76]). The incidence of PPM implantation in the first post-surgical month was 2.707% (95% CI [1.657; 3.952]). Among the four main intervention groups, including valve, maze, valve-maze, and combined surgeries, maze surgery was associated with the highest prevalence (4.93%; CI [3.24; 6.92]). The pooled prevalence of SND among studies was 13.71% (95% CI [8.13; 20.33]). No significant relationship was observed between PPM implantation and age, gender, cardiopulmonary bypass time, or aortic cross-clamp time.ConclusionBased on the present report, patients undergoing the maze and maze-valve procedures are at higher risk of post-op SND, whereas lone valve surgery had the lowest prevalence of PPM implantation.Systematic Review RegistrationPROSPERO (CRD42022341896).

Background Despite the recognized implications of high-density lipoprotein cholesterol (HDL-C) in cardiovascular diseases, the role of body mass index (BMI) in HDL-C association with cardiovascular outcomes remains unclear. This study investigated the possible modifying implications of BMI on the correlation between HDL-C and coronary artery bypass grafting (CABG) outcomes. Methods The present cohort included isolated CABG patients (median follow-up: 76.58 [75.79–77.38] months). The participants were classified into three groups: 18.5 ≤ BMI < 25 (normal), 25 ≤ BMI < 30 (overweight), and 30 ≤ BMI < 35 (obese) kg/m2. Cox proportional hazard models (CPHs) and restricted cubic splines (RCSs) were applied to evaluate the relationship between HDL-C and all-cause mortality as well as major adverse cardio-cerebrovascular events (MACCEs) in different BMI categories. Results This study enrolled a total of 15,639 patients. Considering the final Cox analysis among the normal and overweight groups, HDL-C ≥ 60 was a significant protective factor compared to 40 < HDL-C < 60 for all-cause mortality (adjusted hazard ratio (aHR): 0.47, P: 0.027; and aHR: 0.64, P: 0.007, respectively). However, the protective effect of HDL-C ≥ 60 was no longer observed among patients with 30 ≤ BMI < 35 (aHR: 1.16, P = 0.668). RCS trend analyses recapitulated these findings; among 30 ≤ BMI < 35, no uniform inverse linear association was observed; after approximately HDL-C≈55, its increase was no longer associated with reduced mortality risk. RCS analyses on MACCE revealed a plateau effect followed by a modest rise in overweight and obese patients from HDL-C = 40 onward (nonlinear association). Conclusions Very high HDL-C (≥ 60 mg/dL) was not related to better outcomes among obese CABG patients. Furthermore, HDL-C was related to the post-CABG outcomes in a nonlinear manner, and the magnitude of its effects also differed across BMI subgroups.

Background Obese patients have more coronary artery disease (CAD) risk factors that may affect myocardial function. We aimed to assess the ability of echocardiography‐derived conventional parameters, left atrial strain, and global longitudinal strain to detect early diastolic and systolic dysfunction in obese individuals with almost no CAD risk factors. Method We studied 100 participants with structurally normal hearts, ejection fractions above 50%, almost normal coronary arteries in coronary angiogram (syndrome X), and no cardiovascular risk factor except dyslipidemia. Participants were classified as normal‐weight (BMI < 25.0 kg/m2, n = 28) and high‐weight (BMI ≥ 25.0 kg/m2, n = 72). Conventional echocardiographic parameters and two‐dimensional speckle tracking (2DSTE) were used to measure peak LA strain and global longitudinal strain to evaluate diastolic and systolic function, respectively. Result There was no significant difference in the standard and conventional echocardiographic parameters between the two groups. 2DSTE echocardiographic parameters of the longitudinal deformation of the LV myocardium were not significantly different within the two groups. However, there were significant differences between the subjects with normal‐weight and high‐weight in terms of LA strain (34.51 ± 8.98% vs. 39.06 ± 8.62%, p = .021). The normal‐weight group had lower LA strain, in compression with the high‐weight group. All echocardiographic parameters were in the normal range. Conclusion In the present study we demonstrated that global longitudinal subendocardial deformations, for the evaluation of systolic function, and conventional echocardiographic parameters, for the evaluation of diastolic function, were not significantly different between normal‐ and high‐weight groups. Although LA strain was higher among overweight patients, it was not above the normal range of diastolic dysfunction.

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Background Lead exposure (LE) and its attributable deaths and disability-adjusted life years (DALYs) have declined in the recent decade; however, it remains one of the leading public health concerns, particularly in regions with low socio-demographic index (SDI) such as the North Africa and Middle East (NAME) region. Hence, we aimed to describe the attributable burden of the LE in this region. Methods Data on deaths, DALYs, years of life lost (YLLs), and years lived with disability (YLDs) attributable to LE in the NAME region and its 21 countries from 1990 to 2019 were extracted from the Global Burden of Disease (GBD) 2019 study. Results In 2019, the age-standardized death and DALY rates attributable to LE were 23.4 (95% uncertainty interval: 15.1 to 33.3) and 489.3 (320.5 to 669.6) per 100,000 in the region, respectively, both of which were higher among men than women. The overall age-standardized death and DALY rates showed 27.7% and 36.8% decreases, respectively, between 1990 and 2019. In this period, Bahrain, the United Arab Emirates, and Turkey had the highest decreases in the age-standardized death and DALY rates, while Afghanistan, Egypt, and Yemen had the lowest ones. Countries within high SDI quintile had lower attributable burden to LE compared with the low SDI quintile. Cardiovascular diseases and chronic kidney diseases accounted for the 414.2 (258.6 to 580.6) and 28.7 (17.7 to 41.7) LE attributable DALYs per 100,000 in 2019, respectively. The attributable YLDs was 46.4 (20.7 to 82.1) per 100,000 in 2019, which shows a 25.7% reduction (-30.8 to -22.5%) over 1990–2019. Conclusions The overall LE and its attributed burden by cause have decreased in the region from 1990–2019. Nevertheless, the application of cost-effective and long-term programs for decreasing LE and its consequences in NAME is needed.