Amygdalin/chitosan-polyvinyl alcohol/cerium-tannic acid hydrogel as biodegradable long-time implant for cancer recurrence care applications: An in vitro study.

Cancer recurrence following surgery is a serious and worrying problem for the patient. Common treatment strategies, such as chemotherapy, radiotherapy, and surgery, are restricted because of low uptake of the drugs, poor pharmacokinetic properties, and toxicity issues for healthy tissues. The development of engineering platforms for improving the postoperative treatment of cancer can help solve this problem. In this study, the ceria-tannic acid nanoparticles (CeTA-NPs) were successfully synthesized and characterized. Chitosan-polyvinyl/alcohol (CS-PVA) hydrogels containing CeTA NPs (CS-PVA/CeTA) and amygdalin as an anticancer substance were fabricated using freeze-thaw and immersion-drying techniques. The swelling and degradation behaviors, antibacterial activity, and biocompatibility of as-prepared hydrogel were done. The apoptotic effects of amygdalin/CS-PVA/CeTA hydrogel were evaluated by flow cytometry technique on a human colorectal cancer (SW-480) cell line. The CeTA-NPs were investigated as antibacterial and cross-linker agents for greater stability of the hydrogel network. The CS-PVA/CeTA hydrogel demonstrated good safety and antibacterial activity. The results of swelling and biodegradation suggest that CS-PVA/CeTA hydrogels can inspire long-time application. The anticancer effects of the amygdalin/CS-PVA/CeTA hydrogel were confirmed by apoptosis results. Hence, amygdalin/CS-PVA/CeTA hydrogel can be a promising candidate for long-time biomedical application.

Empagliflozin improves high-sensitive cardiac troponin-I and high-density lipoprotein cholesterol in patients with type 2 diabetes mellitus and coronary artery disease: a post-hoc analysis of EMPA-CARD Trial.

Background: Empagliflozin is a sodium glucose cotransporter-2 (SGLT2) inhibitor that has been suggested to improve cardiac function and vascular recovery. The risk of coronary artery diseases is much higher in diabetic patients and is associated with greater morbidity and mortality. High-sensitivity cardiac troponin-I (hs-cTnI) is an important prognostic biomarker in cardiac diseases. Therefore, this study aimed to investigate the effect of empagliflozin compared to placebo on changes in hs-cTnI and lipid profile after 26 weeks of treatment. Methods: This was an ancillary study in a randomized trial of patients with concomitant type 2 diabetes mellitus (T2DM) and coronary artery disease (CAD) (The EMPA-CARD study). Patients who were already on standard anti-diabetic/anti-ischemic medications were randomized to receive either placebo or empagliflozin 10 mg/daily. Serum hs-cTnI and lipid profile were measured at baseline and after 26 weeks. Results: Of the 95 randomized patients, hs-cTnI and lipid profile were measured for a total of 77 patients. No significant difference was observed regarding the baseline characteristics between the two arms. Compared to placebo, empagliflozin significantly reduced hs-cTnI after 26 weeks (mean difference (MD) of -13.242, 95%CI: -14.151 to -12.333, p < 0.001). In the empagliflozin group, non-significant reductions in total cholesterol, LDL-C, and triglyceride have resulted; however, there was an increase in HDL-C level (MD = 2.40,95%CI:0.16-4.60, p < 0.04). Conclusion: Empagliflozin compared to placebo was superior in reducing circulating hs-cTnI that may indicate improvements in cardiomyocytes function in patients with T2DM and CAD. Moreover, empagliflozin had a modest impact on the serum lipid profile biomarkers. Trial registration: The original EMPA-CARD study has been registered in Iranian Registry of Clinical Trials. www.IRCT.ir, Identifier: IRCT20190412043247N2. Registration Date: 6/13/2020. Registration timing: prospective.

The effect of sodium-glucose co-transporter-2 (SGLT2) inhibitors on blood interleukin-6 concentration: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: The low-grade chronic inflammation in diabetes plays an important role in development of cardiovascular and renal complications. Sodium-glucose co-transporter-2 (SGLT2) inhibitors are recognized as protective agents for cardio-renal complications. Interleukin-6 (IL-6) is positively associated with the pathophysiology of metabolic-related pathologies. The aim of this meta-analysis is to investigate the effect of SGLT2 inhibitors on blood IL-6 concentration in randomized controlled trials (RCTs). METHODS: Embase, PubMed, and Scopus were systematically searched up to 1st of November 2023. The eligible studies were RCTs with adult population that had provided blood IL-6 for both control and intervention groups. Cochrane risk-of-bias tool were for study quality assessment. Data were analyzed using random effect model via Stata statistical software. RESULTS: Eighteen studies with a total of 5311 patients were included. Of which 3222 and 2052 patients were in intervention and control arm, respectively. Of the total population, 49.7% were men. The study durations ranged from 8 to 52 weeks. The pooled analysis showed a significant association between the use of SGLT2 inhibitors and lower IL-6 levels (standardized mean difference (SMD) = -1.04, Confidence Interval (CI): -1.48; -0.60, I2 = 96.93%). Dapagliflozin was observed to have a higher IL-6-lowering effect (SMD = -1.30, CI: -1.89; -0.71, I2 = 92.52) than empagliflozin or canagliflozin. Sub-group analysis of control groups (SMD = -0.58 (-1.01, -0.15) and -1.35 (-2.00, -0.70 for the placebo and active control sub-groups, respectively) and duration of interventions (SMD = -0.78 (-1.28, -0.28) and -1.20 (-1.86, -0.55) for study duration of ≤ 12 and > 12 weeks, respectively) did not change the results. Meta-regression analysis showed a significant correlation between the level of HbA1c and IL-6-lowering efficacy of SGLT2 inhibitors. CONCLUSION: IL-6 levels are significantly reduced with the use of SGLT2 inhibitors with HbA1c as the only marker influencing such reductions, and dapagliflozin had the highest potency. The anti-inflammatory effect of SGLT2 inhibitors supports their broader use to address diabetic complications related to inflammatory responses.

The synthesis and development of poly(ε-caprolactone) conjugated polyoxyethylene sorbitan oleate-based micelles for curcumin drug release: an in vitro study on breast cancer cells.

BACKGROUND: it is now known that curcumin (Cur) has a broad range of biological properties; however, photosensitivity, as well as low bioavailability and short half-life, have limited its clinical application. To overcome these problems the synthesis of poly(ε-caprolactone)-Tween 80 (PCL-T) copolymers was performed. METHODS: the copolymers of PCL-T were created using the solvent evaporation/extraction technique. Then Cur was loaded in PCL-T micelles (PCL-T-M) by a self-assembly method. The characterization of copolymer and micelles was assessed by gel permeation chromatography (GPC), Fourier transform infrared spectroscopy (FT-IR), proton nuclear magnetic resonance spectroscopy (1HNMR), differential scanning calorimetry (DSC), transmission electron microscopy (TEM), and dynamic light scattering (DLS) methods. The MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay was used to indicate the cytotoxicity of the free Cur, PCL-T-M, and Cur-loaded PCL-T-M. RESULTS: TEM analysis showed monodispersed and spherical shapes with a size of about 90 nm. Cur was released from PCL-T-M at pH 7.4 (45%) and 5.5 (90%) during 6 days. After 24 and 48 h, the IC50 of the free Cur, PCL-T-M, and Cur-loaded PCL-T-M on MCF-7 cells were 80.86 and 54.45 µg mL-1, 278.30 and 236.19 µg mL-1, 45.47 and 19.05 µg mL-1, respectively. CONCLUSION: this study showed that, in the same concentration, the effectiveness of the Cur-loaded PCL-T-M is more than the free Cur, and the nano-system has been able to overcome delivery obstacles of Cur drug. Thus, PCL-T-M can be a candidate as a drug carrier for the delivery of Cur and future therapeutic investigations on breast cancer.

The effect of dietary approaches to stop hypertension and ketogenic diets intervention on serum uric acid concentration: a systematic review and meta-analysis of randomized controlled trials.

Hyperuricemia as a risk factor for metabolic diseases is proved to be profoundly modified by dietary approaches. This systematic review and meta-analysis of randomized control trials (RCT) was conducted to investigate the effect of two nutritional interventions; dietary approaches to stop hypertension (DASH) diet and ketogenic diet (KD) on serum uric acid (UA) concentrations. Our systematic search was for RCTs in which KD or DASH diet were assigned to adults for at least 2 weeks or more. Until March 2023 in Embase, Web of Science, PubMed, and Scopus databases, 10 eligible RCTs that intervened with DASH diet (n = 4) or KD (n = 6) and had provided laboratory data on serum UA were found. Summary effect was calculated by random-effects model. Results from the meta-analysis of the 4 DASH diet RCTs with a total of 590 participants revealed significant decrease in serum UA after at least 4 weeks of interventions (mean difference (MD) = ‒0.25; 95% CI ‒0.4 to ‒0.1 mg/dL; p < 0.01; I2 = 0%). The pooled meta-analysis of the 6 included RCTs of KD reporting data of 267 participants showed no significant changes in serum UA (MD = 0.26; 95% CI ‒0.47 to 0.98 mg/dL, I2 = 95.32%). However, a non-significant reduction of UA in the subgroup analysis of very low-calorie KD (VLCKD) studies (MD = ‒0.04; 95% CI ‒0.29 to 0.22, I2 = 0%) was obtained. DASH diet has an ameliorating effect on serum UA and may be recommended for hyperuricemia states such as gout. In addition, we have shown that serum UA level following KD remained unchanged. Although, in view of the heterogeneity across the studies, further investigations are needed to determine the effect of KD and VLKD on serum UA concentrations.

Postmortem Histopathologic Findings and SARS-CoV-2 Detection in Autopsy Kidneys of Patients With COVID-19: A Systematic Review and Meta-Analysis.

OBJECTIVES: This systematic review and meta-analysis aimed to investigate the prevalence of postmortem kidney histopathologic features of patients with coronavirus disease 2019 (COVID-19) in addition to the rate of renal tropism in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: We searched Web of Science, PubMed, Embase, and Scopus up to September 2022 to identify eligible studies. A random-effects model was used to estimate the pooled prevalence. Cochran Q test and Higgins I2 were used to assess evidence of heterogeneity. RESULTS: In total, 39 studies were included in the systematic review. The meta-analysis included 35 studies consisting of a total of 954 patients, with an average age of 67.1 years. The pooled prevalence of acute tubular injury (ATI)-related changes was the predominant finding (85% [95% confidence interval, 71%-95%]), followed by arteriosclerosis (80%), vascular congestion (66%), and glomerulosclerosis (40%). Endotheliitis (7%), fibrin microthrombi (12%), focal segmental glomerulosclerosis (1%), and calcium crystal deposits (1%) were seen in a smaller number of autopsies. The overall average rate of virus detection was 47.79% in the pooled data of 21 studies (272 samples). CONCLUSIONS: The main finding-ATI-correlated to clinical COVID-19-associated acute kidney injury. The presence of SARS-CoV-2 in kidney samples in addition to vascular lesions in kidneys can be linked to direct kidney invasion by the virus.

Low dose ultra-slow infusion thrombolytic therapy (LDUSITT) as an alternative option in a COVID-19 patient with free-floating right atrial thrombus: a case report and review of literature.

The hyper-coagulopathy nature of COVID-19 is a prevalent consequence among patients. Free-floating right atrial thrombi are a relatively rare finding and the optimal therapy is a therapeutic dilemma.We present a 37-year-old woman with acute dyspnea and fatigue. Several ground glass opacities were shown on computed tomography of chest that further proved to be associated with severe COVID-19 disease. A transthoracic echocardiography revealed a mobile right atrial mass with bilateral pulmonary embolism. She was considered high risk for surgical therapy by cardiovascular surgeons. She was then started on anticoagulation therapy for 5 days however the size regression of the thrombus remained unchanged. A regimen of low dose (24 mg) ultra-slow (24 h) intravenous infusion of alteplase, without bolus was initiated. Following the third day of thrombolytic therapy, the control echocardiography demonstrated complete resolution of the thrombus.Prolonged infusion of low dose fibrinolytics can be an alternative treatment to surgery for right heart thrombi.

The effect of EMPAgliflozin on markers of inflammation in patients with concomitant type 2 diabetes mellitus and Coronary ARtery Disease: the EMPA-CARD randomized controlled trial.

Systemic inflammation and oxidative burden in patients with type 2 diabetes mellitus (T2DM) causes deleterious cardiovascular outcomes. We sought to investigate the clinical antioxidative and anti-inflammatory effects of empagliflozin. Platelet function, oxidant and antioxidant biomarkers and pro-inflammatory agents at baseline and at 26 weeks were measured. A total of 95 patients (41.05% male, mean age 62.85 ± 7.91 years, mean HbA1c 7.89 ± 0.96%) with concomitant T2DM and coronary artery disease (CAD) were randomized (1:1) to receive empagliflozin (10 mg/daily) or placebo. Patients treated with empagliflozin had lower levels of interleukin 6 (IL-6) (adjusted difference (adiff): - 1.06 pg/mL, 95% CI - 1.80; - 0.32, P = 0.006), interleukin 1ß (IL-1ß) and high-sensitive C-reactive protein (Hs-CRP) (adiff: - 4.58 pg/mL and - 2.86 mg/L; P = 0.32 and 0.003, respectively) compared to placebo. There were elevations in super oxidase dismutase (SOD) activity, glutathione (GSHr), and total antioxidant capacity (TAC) with empagliflozin (adiff: 3.7 U/mL, 0.57 muM, and 124.08 mmol/L, 95% CI 1.36; 6.05, 0.19; 0.95, and 47.98; 200.18, P = 0.002, 0.004, and 0.002, respectively). While reactive oxygen species (ROS) improved significantly (adiff: - 342.51, 95% CI - 474.23; - 210.79, P < 0.001), the changes in catalase activity (CAT), malondialdehyde (MDA), or protein carbonyl groups (PCG) were not significant. Moreover, the P-selectin antigen expression on platelet surface was significantly reduced (adiff: - 8.81, 95% CI - 14.87; - 2.75, P = 0.005). Markers of glycemic status (fasting blood glucose, HbA1c, and HOMA-IR (homeostatic model assessment for insulin resistance) significantly improved (P < 0.001). Among patients with T2DM and CAD, 6-month treatment with empagliflozin can mitigate inflammation, platelet activity and oxidative stress and is associated with clinical cardiovascular benefits.Trial Registration Iranian Registry of Clinical Trials. www.IRCT.ir , Identifier: IRCT20190412043247N2. Registration Date: 6/13/2020. Registration timing: prospective.

Fatal overdose from injection of human growth hormone; a case report and review of the literature.

BACKGROUND: Human growth hormone (HGH) is a categorized as a performance-enhancing substance. HGH has been abused by athletes for doping purposes. CASE PRESENTATION: We present a first lethal case of HGH acute toxicity. A young-agitated-athlete with a history of somatropin for the past 2-year, who had hallucinations referred to the emergency department reporting to have abused of 300 mg subcutaneous injections of HGH. He was tachycardic with mild hypertension. Lab data revealed hypernatremia (157 mEq/L), hyperkalemia (5.3 mEq/L), high LDH (1448 U/L), and CPK (2620 U/L), in favor of rhabdomyolysis. Routine drug screening tests were negative for all substances. He was intubated due to low O2 saturation and progressive loss of consciousness. After several episodes of hyperthermia, hypertension, and possibly pulmonary embolism, he died subsequent to somatropin overdose. CONCLUSIONS: Complications of HGH misuse can be life-threatening and athletes should be warned of its deleterious effects.

Study rationale and design of a study of EMPAgliflozin's effects in patients with type 2 diabetes mellitus and Coronary ARtery disease: the EMPA-CARD randomized controlled trial.

BACKGROUND: Recent trials have revealed that sodium-glucose co-transporter 2 inhibitors (SGLT2-i) are effective against hyperglycemia and also reduce micro- and macro-vascular complications in patients with type 2 diabetes mellitus (T2DM). Most of the beneficial cardiovascular effects have been investigated in patients with heart failure and coronary artery disease (CAD). Yet, few human studies have been conducted to investigate the molecular mechanisms underlying these clinically beneficial effects in patients with CAD. Accordingly, the EMPA-CARD trial was designed to focus on the molecular effects of empagliflozin in patients with T2DM and CAD. METHODS: In this multicenter, triple-blind randomized controlled trial, patients with documented known T2DM and CAD will be recruited. They will be randomized on a 1:1 ratio and assigned into two groups of empagliflozin 10 mg/daily and placebo. The primary endpoint is the effect of empagliflozin on changes of plasma interleukin 6 (IL-6) after 26 weeks of treatment. The secondary endpoints will consist of changes in other inflammatory biomarkers (Interleukin 1-beta and high-sensitive C-reactive protein), markers of oxidative stress, platelet function, and glycemic status. DISCUSSION: The EMPA-CARD trial mainly tests the hypothesis that SGLT2 inhibition by empagliflozin may improve inflammatory status measured as reduction in inflammatory biomarkers in patients with T2DM and CAD. The results will provide information about the underlying mechanisms of SGLT2 inhibition that mediate the beneficial effects of this medication on clinical outcomes. TRIAL REGISTRATION: Iranian Registry of Clinical Trials. www.IRCT.ir , Identifier: IRCT20190412043247N2. Registration Date: 6/13/2020. Registration timing: prospective.

Association between ST-segment resolution after primary angioplasty and short-term outcomes in patients with acute myocardial infarction.

BACKGROUND: The aim of this study was to evaluate the relationship between the early/late complete ST-resolution and short-term cardiovascular outcomes in patients undergoing primary angioplasty. METHODS: This was a prospective cross-sectional study of patients with acute myocardial infarction who candidate for primary percutaneous coronary intervention (PCI) during 1 year. An ECG obtained at the time of admission, 90 minutes and 24 hour after PCI. Patients were followed up for in hospital and 1-year outcomes and then data assessed according to the ST segment resolution (STR) (complete ≥70% and incomplete <70% STR). RESULTS: Overall, 124 patients included in the study. The rates of complete STR were 44.4% after 90 minutes and 82.3% after 24 hours. Patients with early complete STR had significant lower rates of heart failure after 1-year follow-up (32% versus 46%, OR: 1.88, 95% CI: 1.42-2.50, P=0.005) but not like patients with late STR. No significant relationship was observed between early/late complete STR and re-infarction, stroke, re-hospitalization and death during 1-year follow-up (P>0.05). Moderate correlations were found between percentage of ST resolution after 90 minutes and EF before discharge and final EF (correlation coefficient: 0.395 and 0.488, respectively, P<0.001). CONCLUSIONS: Early complete STR can be an indicator for development of heart failure after 1-year follow-up.

Risk Factors Associated with Heart Valve Thrombosis in Patients with Prosthetic Heart Valve Dysfunction.

BACKGROUND: Thrombotic and thromboembolic events are important causes of mortality and morbidity in patients with prosthetic heart valve. The aim of this study is to evaluate the factors that may contribute to prosthetic heart valve thrombosis. METHODS: This was a cross-sectional study in Rajaie Heart Center on patients with prosthetic heart valve malfunction, within a year. According to the echocardiographic and fluoroscopic findings, the patients were divided into two groups (thrombosis and non-thrombosis groups). The patients' demographic, clinical and laboratory data were recorded and analyzed with SPSS software. RESULTS: A total of 142 patients participated in this study. Ninety-four patients (66.2%) were diagnosed with thrombosis. There was a significant relationship between thrombosis and inadequate anti-coagulation (international normalized rati [INR] <2.5) (odds ratio [OR]: 4.15, 95% CI: 1.98-9.87, P = 0.003), history of infection (OR: 12.81, 95% CI: 3.52-19.02, P<0.001), prothrombin time (PT) check interval (OR: 2.38, 95% CI: 1.63-8.47, P = 0.019), atrial fibrillation (AF) rhythm (OR: 3.96, 95% CI: 1.75-8.09, P = 0.019), and plasma fibrinogen level (OR: 6.90, 95% CI: 2.58-14.69). CONCLUSION: Based on this study, inadequate anti-coagulation, AF rhythm, recent infection and plasma fibrinogen level were the factors most contributing to prosthetic valve thrombosis. As there were many cases of thrombosis in patients with history of infection, this factor can be considered for risk assessment in prosthetic valve.

The effect of colchicine on the echocardiographic constrictive physiology after coronary artery bypass graft surgery.

BACKGROUND: Constrictive physiology is a transitory condition that could lead to constrictive pericarditis, which is a rare complication after open-heart surgery. Anti-inflammatory drugs like colchicine are recommended for prevention of constrictive pericarditis; however, there is no evidence about the effect of colchicine on constrictive pericarditis. Thus, the aim of this study is to evaluate the preventive effect of colchicine on the incidence of echocardiographic constrictive physiology after open-heart surgery. METHODS: This was a parallel randomized, double-blind trial. Patients were randomly assigned to receive 1 mg colchicine once-daily from 48 hours before and 0.5 mg twice daily for 5 days after surgery. Primary outcome was the incidence of the constrictive physiology after primary endpoint (1 week after the surgery). The secondary outcome was the primary outcome after secondary endpoint (4 weeks after surgery) plus the new cases of constrictive physiology between the primary and secondary endpoints. RESULTS: Out of 160 participating patients, the primary outcome occurred in 19 patients (23%) in placebo and 11 (13%) in intervention groups. There was no significant difference between two groups (P = .106). After 4 weeks of follow-up, 19 patients (23%) in placebo and 9 (11%) in intervention groups had constrictive physiology whereas 2 out of 11 patients (18.2%) were recovered. The difference was significant (P = .038). No new case of constrictive physiology occurred between primary and secondary endpoints. CONCLUSION: Short-term use of colchicine has a preventive effect on reducing constrictive physiology after 1 month of open-heart surgery but not a week after that.

Comparison of fenofibrate and pioglitazone effects on patients with nonalcoholic fatty liver disease.

INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) is known to be a health-related problem; there is no proven treatment for NAFLD. However, a wide range of possible therapies have been proposed and studied. In the current study, we aimed to compare the therapeutic effects of fenofibrate and pioglitazone on NAFLD. PATIENTS AND METHODS: In this randomized clinical trial study (ethic number: ZUMS.REC.1393.133), patients with NAFLD and alanine aminotransferase in range of 1-1.5 folds of normal and BMI (25-35) were studied. Blood lipids and liver enzymes were measured. The patients were divided randomly into three groups (recipient of fenofibrate, pioglitazone, and exercise). After the patients completed the course of treatment, liver enzymes were measured. RESULTS: According to the results of this study, 90 patients with NAFLD were divided into three groups of 30 patients. All variables at the beginning of the study showed no significant difference among the three groups, but after the treatment period, the results showed that the levels of alanine aminotransferase, aspartate transaminase, systolic blood pressure, diastolic blood pressure, and BMI changed significantly: the levels decreased in all groups. CONCLUSION: This study showed beneficial effects of fenofibrate and pioglitazone in patients with fatty liver. Further studies with larger study populations on the effects of these drugs on fatty liver, lipid profile, blood glucose, and insulin are suggested.