Background. Hydroxychloroquine with or without azithromycin was one of the common therapies at the beginning of the COVID-19 pandemic. They can prolong QT interval, cause torsade de pointes, and lead to sudden cardiac death. We aimed to assess QT interval prolongation and its risk factors in patients who received hydroxychloroquine with or without azithromycin. Methods. This study was a retrospective cohort study. One hundred seventy-two confirmed COVID-19 patients were included in this study, hospitalized at Babol University of Medical Sciences hospitals between March 5, 2020, and April 3, 2020. Patients were divided into two groups: hydroxychloroquine alone and hydroxychloroquine with azithromycin. Electrocardiograms were used for outcome assessment. Results. 83.1% of patients received hydroxychloroquine plus azithromycin vs. 16.9% of patients who received only hydroxychloroquine. The mean age of patients was 59.2 ± 15.4 .The mean of posttreatment QTc interval in the monotherapy group was shorter than the mean of posttreatment QTc interval in the combination therapy group, but it had no significant statistical difference ( 462.5 ± 43.1 milliseconds vs. 464.3 ± 59.1 milliseconds; p = 0.488 ). Generally, 22.1% of patients had a prolonged QTc interval after treatment. Male gender, or baseline QTc ≥ 450 milliseconds, or high-risk Tisdale score increased the likelihood of prolonged QTc interval. Due to QTc prolongation, fourteen patients did not continue therapy after four days. Conclusions. Hospitalized patients treated by hydroxychloroquine with or without azithromycin had no significant difference in prolongation of QT interval and outcome. The numbers of patients with prolonged QT intervals in this study emphasize careful cardiac monitoring during therapy, especially in high-risk patients.

Kynurenine pathway is the main route of tryptophan metabolism and produces several metabolites with various biologic properties. It has been uncovered that several cardiovascular diseases are associated with the overactivation of kynurenine pathway and kynurenine and its metabolites have diagnostic and prognostic value in cardiovascular diseases. Furthermore, it was found that several kynurenine metabolites can differently affect cardiovascular health. For instance, preclinical studies have shown that kynurenine, xanthurenic acid and cis-WOOH decrease blood pressure; kynurenine and 3-hydroxyanthranilic acid prevent atherosclerosis; kynurenic acid supplementation and kynurenine 3-monooxygenase (KMO) inhibition improve the outcome of stroke. Indoleamine 2,3-dioxygenase (IDO) overactivity and increased kynurenine levels improve cardiac and vascular transplantation outcomes, whereas exacerbating the outcome of myocardial ischemia, post-ischemic myocardial remodeling, and abdominal aorta aneurysm. IDO inhibition and KMO inhibition are also protective against viral myocarditis. In addition, dysregulation of kynurenine pathway is observed in several conditions such as senescence, depression, diabetes, chronic kidney disease (CKD), cirrhosis, and cancer closely connected to cardiovascular dysfunction. It is worth defining the exact effect of each metabolite of kynurenine pathway on cardiovascular health. This narrative review is the first review that separately discusses the involvement of kynurenine pathway in different cardiovascular diseases and dissects the underlying molecular mechanisms.

Sestrin2 is a stress-inducible metabolic regulator and a conserved antioxidant protein which has been implicated in the pathogenesis of several diseases. Sestrin2 can protect against atherosclerosis, heart failure, hypertension, myocardial infarction, stroke, spinal cord injury neurodegeneration, nonalcoholic fatty liver disease (NAFLD), liver fibrosis, acute kidney injury (AKI), chronic kidney disease (CKD), and pulmonary inflammation. Oxidative stress and cellular damage signals can alter the expression of Sestrin2 to compensate for organ damage. Different stress signals such as those mediated by P53, Nrf2/ARE, HIF-1α, NF-κB, JNK/c-Jun, and TGF-β/Smad signaling pathways can induce Sestrin2 expression. Subsequently, Sestrin2 activates Nrf2 and AMPK. Furthermore, Sestrin2 is a major negative regulator of mTORC1. Sestrin2 indirectly regulates the expression of several genes and reprograms intracellular signaling pathways to attenuate oxidative stress and modulate a large number of cellular events such as protein synthesis, cell energy homeostasis, mitochondrial biogenesis, autophagy, mitophagy, endoplasmic reticulum (ER) stress, apoptosis, fibrogenesis, and lipogenesis. Sestrin2 vigorously enhances M2 macrophage polarization, attenuates inflammation, and prevents cell death. These alterations in molecular and cellular levels improve the clinical presentation of several diseases. This review will shed light on the beneficial effects of Sestrin2 on several diseases with an emphasis on underlying pathophysiological effects.

Thymoquinone (TQ) is one of the components extracted from Nigella sativa seeds and has antioxidant, anti-inflammatory, and anticancer effects. We evaluated the effect of TQ on 5-fluorouracil (5-FU) pharmacokinetics (PK) in vivo and in vitro on human colorectal cancer cell line. Ten Adult male Wistar rats were assigned to two groups. TQ treated group received intraperitoneal TQ once daily for 14 consecutive days (5 mg/kg). Both groups received intraperitoneal 5-FU (50 mg/kg) on day 15 and blood samples were collected from retro-orbital plexus. The pharmacokinetics parameters were analyzed using high-performance liquid chromatography (HPLC). Moreover, various concentrations of 5-FU, TQ, and combination of 5-FU and TQ were added to the HT-29 cell line and cell viability was measured using 3- (4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide colorimetric assay. The maximum serum concentration ( Cmax), area under the curve (AUC), and time of maximum concentration ( Tmax) of 5-FU in TQ treated group were significantly increased approximately by 61, 60, and 24% compared to the control group, respectively. The combination of 5-FU with TQ (0.284 mM) showed a greater inhibitory effect on HT-29 cell growth compared to the alone 5-FU (0.027 and 0.055 mM) administration. TQ increases the AUC, Cmax, and Tmax of 5-FU and has a synergistic effect on the PK of 5-FU. Moreover, low concentration of TQ enhances the inhibitory effects of 5-FU on cell growth in colorectal cancer cell line. This synergistic effect might enhance the anticancer effects of low concentration of 5-FU, leading to drug dose reduction and reduced systemic toxicity of this chemotherapeutic agent.

This Study describes eleven patients positive for severe acute respiratory syndrome coronavirus 2. In our cases, females and younger patients developed more severe disease. In contrast, improvement in left ventricular ejection fraction and N‐terminal prohormone brain natriuretic peptide within the first week of treatment contributed to promising outcomes.