The association between C-reactive protein and coronary artery calcification: a systematic review and meta-analysis.

BACKGROUND: While coronary artery calcification (CAC) is recognized as a reliable marker for coronary atherosclerosis, the relationship between the concentration of C-reactive protein (CRP) and the incidence and progression of CAC remains controversial. METHOD: PubMed, Embase, Web of Science, and Scopus were systematically searched to identify relevant observational studies until October 2023. The methodological quality of the included studies was evaluated using the Newcastle-Ottawa Scale (NOS). A random-effects meta-analysis was employed to calculate pooled odd ratios (OR) and corresponding 95% confidence intervals, considering heterogeneity among the studies. RESULTS: Out of the 2545 records, 42 cross-sectional and 9 cohort studies were included in the systematic review. The meta-analysis on 12 eligible cross-sectional studies revealed no significant association between CAC and CRP [pooled OR: 1.03 (1.00, 1.06)]. Additionally, an insignificant association was found between CAC and CRP through meta-analysis on three eligible cohort studies [pooled OR: 1.05 (0.95, 1.15)] with no considerable heterogeneity across studies. Sensitivity analyses indicated that the meta-analysis models were robust. There was no evidence of publication bias. CONCLUSION: Based on the meta-analysis findings, elevated levels of CRP did not emerge as a valuable prognostic maker for CAC incidence and progression prediction.

Cardiac troponins and coronary artery calcium score: a systematic review.

An early diagnosis of atherosclerosis, particularly in subclinical status, can play a remarkable role in reducing mortality and morbidity. Because of coronary artery calcification (CAC) nature in radiation exposure, finding biomarkers associated with CAC could be useful in identifying individuals at high risk of CAC score. In this review, we focused on the association of cardiac troponins (hs-cTns) and CAC to achieve insight into the pathophysiology of CAC. In October 2022, we systematically searched Web of Science, Scopus, PubMed, and Embase databases to find human observational studies which have investigated the association of CAC with cardiac troponins. To appraise the included articles, we used the Newcastle Ottawa scale (NOS). Out of 520 records, 10 eligible studies were included. Based on findings from longitudinal studies and cross-sectional analyses, troponin T and I were correlated with occurrence of CAC and its severity. Two of the most important risk factors that affect the correlation between hs-cTns serum levels and CAC were age and gender. The elevation of cardiac troponins may affect the progression of CAC and future cardiovascular diseases. Verifying the association between cardiac troponins and CAC may lead to identify individuals exposed to enhanced risk of cardiovascular disease (CVD) complications and could establish innovative targets for pharmacological therapy.

Non-HDL cholesterol and long-term follow-up outcomes in patients with metabolic syndrome.

BACKGROUND: Non-high-density lipoprotein-cholesterol (non-HDL-C) has been identified as a potential biomarker for metabolic syndrome (MetS). However, its predictive capability for MetS varies among different ethnic groups, necessitating further investigation. This study aimed to assess the role of non-HDL-C in the early diagnosis of MetS in the Iranian population through a longitudinal study with a 10-year follow-up period. METHODS: Our study enrolled 4684 individuals from the MASHAD (Mashhad Stroke and Heart Atherosclerotic Disorder) cohort who were followed for 10 years to examine the association between non-HDL-C and the incidence of MetS. Additionally, the contribution of individual MetS components to the overall burden was evaluated. RESULTS: A total of 1599 subjects developed MetS, while 3085 did not. Non-HDL-C levels ≥ 130 were associated with a 42% higher risk of developing MetS (relative risk (RR), 1.42; 95% confidence interval (CI), 1.25-1.62). Regarding MetS components, elevated waist circumference (WC) showed the strongest association with MetS incidence (RR, 2.32; 95% CI, 1.45-2.9), whereas triglyceride (TG) levels ≥ 150 mg/dL demonstrated the weakest association (RR, 1.23; 95% CI, 1.04-1.46). Additionally, higher HDL-C levels were reported to be 20% protective against the risk of MetS (RR, 0.8; 95% CI, 0.73-0.86). Moreover, fasting blood glucose (FBG) levels ≥ 100 mg/dL were not significantly linked to MetS burden, while systolic blood pressure (BP) levels ≥ 130 mmHg or diastolic BP levels ≥ 85 mmHg increased the risk of MetS incidence (RR, 1.25; 95% CI: 1.11-1.41). CONCLUSIONS: Elevated non-HDL-C and increased WC serve as significant predictors of MetS in Iranians. Strategies targeting non-HDL-C levels and weight loss should be emphasized to mitigate the risk of MetS development.

Evaluation of berberine pellet effect on clinical recovery time in COVID-19 outpatients: A pilot clinical trial.

Objective: Severe disease onset of COVID-19 may result in alveolar injury and respiratory failure. Apoptosis and inflammation are the main causes of respiratory distress syndrome. Berberine is used in medicine as an analgesic, anti-asthmatic, anti-inflammatory, and antiviral. In the current investigation, the effect of berberine on COVID-19 outpatients was studied. Materials and Methods: The present clinical trial was performed on 40 outpatients who were randomly assigned to berberine (300 mg, TID, 2 weeks) (n=19) or placebo groups (n=21). Both groups received standard therapy and they were monitored on days 3, 7, and 14 after the beginning of the therapy for clinical symptoms' improvement, quantitative CRP, lymphopenia, CBC, and SpO2. The severity and frequency of these symptoms and the level of the parameters were statistically compared between the two groups. Results: On days (0, 3, 7, and 14, there was no significant difference between the berberine and placebo groups in the improvement of clinical symptoms (cough, shortness of breath, nausea, loss of smell and taste, diarrhea, dizziness, sore throat, stomachache, body aches, and body temperature), quantitative CRP, lymphopenia, WBC, neutrophils, platelets, or SpO2. Conclusion: Berberine (300 mg, TID, two weeks) is ineffective in treating COVID-19. More research with a larger sample size is needed to investigate different berberine dosages in other pharmaceutical formulations.

Predictive value of lipoprotein(a) in coronary artery calcification among asymptomatic cardiovascular disease subjects: A systematic review and meta-analysis.

AIMS: Studies have indicated inconsistent results regarding the association between plasma levels of Lipoprotein(a) [Lp(a)] and coronary artery calcification (CAC). We performed a systematic review and meta-analysis to investigate the association between elevated levels of Lp(a) and risk of CAC in populations free of cardiovascular disease (CVD) symptoms. DATA SYNTHESIS: PubMed, Web of Science, Embase, and Scopus were searched up to July 2022 and the methodological quality was assessed using Newcastle-Ottawa Scale (NOS) scale. Random-effects meta-analysis was used to estimate pooled odds ratio (OR) and 95% confidence interval. Out of 298 studies, data from 8 cross-sectional (n = 18,668) and 4 cohort (n = 15,355) studies were used in meta-analysis. Cohort studies demonstrated a positive significant association between Lp(a) and CAC, so that individuals with Lp(a)≥30-50 exposed to about 60% risk of CAC incidence compared to those with lower Lp(a) concentrations in asymptomatic CVD subjects (OR, 1.58; 95% CI, 1.38-1.80; l2, 0.0%; P, 0.483); Subgroup analysis showed that a cut-off level for Lp(a) measurement could not statistically affect the association, but race significantly affected the relationship between Lp(a) and CAC (OR,1.60; 95% CI, 1.41-1.81). Analyses also revealed that both men and women with higher Lp(a) concentrations are at the same risk for increased CAC. CONCLUSIONS: Blood Lp(a) level was significantly associated with CAC incidence in asymptomatic populations with CVD, indicating that measuring Lp(a) may be a useful biomarker for diagnosing subclinical atherosclerosis in individuals at higher risk of CAC score. PROSPERO REGISTRATION NUMBER: CRD42022350297.

Accelerated Wound Healing with a Diminutive Scar through Cocrystal Engineered Curcumin.

Pharmaceutical cocrystals ( Regulatory Classification of Pharmaceutical Co-Crystals Guidance for Industry; Food and Drug Administration, 2018) are crystalline solids produced through supramolecular chemistry to modulate the physicochemical properties of active pharmaceutical ingredients (APIs). Despite their extensive development in interdisciplinary sciences, this is a pioneering study on the efficacy of pharmaceutical cocrystals in wound healing and scar reducing. Curcumin-pyrogallol cocrystal (CUR-PYR) was accordingly cherry-picked since its superior physicochemical properties adequately compensate for limitative drawbacks of curcumin (CUR). CUR-PYR has been synthesized by a liquid-assisted grinding (LAG) method and characterized via FT-IR, DSC, and PXRD analyses. In vitro antibacterial study indicated that CUR-PYR cocrystal, CUR+PYR physical mixture (PM), and PYR are more effective against both Gram-negative (Pseudomonas aeruginosa and Escherichia coli) and Gram-positive (Staphylococcus aureus and Bacillus subtilis) bacteria in comparison with CUR. In vitro results also demonstrated that the viability of HDF and NIH-3T3 cells treated with CUR-PYR were improved more than those received CUR which is attributed to the effect of PYR in the form of cocrystal. The wound healing process has been monitored through a 15 day in vivo experiment on 75 male rats stratified into six groups: five groups treated by CUR-PYR+Vaseline (CUR-PYR.ung), CUR+PYR+Vaseline (CUR+PYR.ung), CUR+Vaseline (CUR.ung), PYR+Vaseline (PYR.ung), and Vaseline (VAS) ointments and a negative control group of 0.9% sodium chloride solution (NS). It was revealed that the wounds under CUR-PYR.ung treatment closed by day 12 postsurgery, while the wounds in other groups failed to reach the complete closure end point until the end of the experiment. Surprisingly, a diminutive scar (3.89 ± 0.97% of initial wound size) was observed in the CUR-PYR.ung treated wounds by day 15 after injury, followed by corresponding values for PYR.ung (12.08 ± 2.75%), CUR+PYR.ung (13.89 ± 5.02%), CUR.ung (16.24 ± 6.39%), VAS (18.97 ± 6.89%), and NS (20.33 ± 5.77%). Besides, investigating histopathological parameters including inflammation, granulation tissue, re-epithelialization, and collagen deposition signified outstandingly higher ability of CUR-PYR cocrystal in wound healing than either of its two constituents separately or their simple PM. It was concluded that desired solubility of the prepared cocrystal was essentially responsible for accelerating wound closure and promoting tissue regeneration which yielded minimal scarring. This prototype research suggests a promising application of pharmaceutical cocrystals for the purpose of wound healing.

Effect of citalopram and sertraline on the expression of miRNA- 124, 132, and 16 and their protein targets in patients with depression.

Objectives: This study aimed to evaluate the effect of SSRIs on the expression of miRNAs and their protein targets. Materials and Methods: In a 100 day open-label study of citalopram (n=25) and sertraline (n=25), levels of miRNA 16, 132, and 124 and glucocorticoid receptor (GR), Brain-derived neurotrophic factor (BDNF), and serotonin transporter (SERT) protein expression were measured by QRT-PCR and western blot in healthy control (n=20), patients with depression at the baseline, and same patients after 100 days of treatment. Results: Expression levels of GR and BDNF proteins were lower in the depressed group before treatment as compared with the healthy group (P<0.0001). The SERT level was higher among the depressed group before treatment in comparison with the healthy group (P<0.0001). The level of GR and BDNF significantly increased, and SERT expression decreased after receiving sertraline (P<0.05). When the depressed group received citalopram, only SERT and GR were altered (P<0.05). Among the microRNAs' expression investigated, mir-124 and mir-132 were higher, and mir-16 was lower among the depressed compared with the healthy group (P<0.0001). Individuals receiving citalopram only showed an increase in the expression of mir-16 while administration of sertraline led to a significant increase in the expression of mir-16 and a decrease in mir-124 and mir-132 (P<0.05). Conclusion: This elucidated the relationship between antidepressant treatment and the expression of different microRNA that control gene expression in various pathways involved in depressed patients. Receiving SSRI can affect the level of these proteins and their relevant microRNAs.

HDL-cholesterol concentration and its association with coronary artery calcification: a systematic review and meta-analysis.

BACKGROUND: Coronary artery calcification (CAC) is a potential risk marker of coronary atherosclerosis that has high specificity and sensitivity. However, the association between high-density lipoprotein cholesterol (HDL-C) concentration and CAC incidence and progression is controversial. METHODS: PubMed, Embase, Web of Science, and Scopus were systematically searched to identify relevant observational studies up to March 2023 and assessed the methodological quality using Newcastle-Ottawa Scale (NOS) scale. Random-effects meta-analysis was used to estimate pooled odds ratios (OR) and 95% confidence interval considering heterogeneity across studies. RESULTS: Of the 2,411 records, 25 cross-sectional (n = 71,190) and 13 cohort (n = 25,442) studies were included in the systematic review. Ten cross-sectional and eight cohort studies were not eligible and were omitted from the meta-analysis. A total of 15 eligible cross-sectional studies (n = 33,913) were included in the meta-analysis and pooled results revealed no significant association between HDL-C and CAC > 0, CAC > 10, or CAC > 100 [pooled OR: 0.99 (0.97, 1.01)]. Meta-analysis of the 5 eligible prospective cohort studies (n = 10,721) revealed no significant protective effect of high HDL-C against CAC > 0 [pooled OR: 1.02 (0.93, 1.13)]. CONCLUSIONS: According to this analysis of observational studies, high HDL-C levels were not found to predict protection against CAC. These results suggest HDL quality rather than HDL quantity is important for certain aspects of atherogenesis and CAC. REGISTRATION NUMBER: CRD42021292077.

Efficacy and Safety of Valproic Acid in Myelodysplastic Syndrome and Acute Myeloid Leukemia; a Narrative Review.

Loads of new therapeutic regimes have been turned up to manage Myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), particularly in elderly patients who are unfit for intensive chemotherapy. Despite accumulating research, the best MDS and AML management approach is indeterminate. Myelodysplastic syndrome implies a group of various hematopoietic stem cell disorders that may progress to acute myeloid leukemia. These disorders are more frequent in older adults. To the high rate of morbidity and abundant toxicities related to the therapeutic approaches, also, the treatment would be challenging. The clinical effectiveness of valproic acid, a histone deacetylase inhibitor, in MDS and AML patients is unknown, even though it has demonstrated positive activities to promote differentiation and apoptosis in cancer cells. We investigated the clinical research on the effects of valproic acid in conjunction with various drugs, including low-dose cytarabine, all-trans retinoic acid, DNA-hypomethylating agents, hydrazine, and theophylline. We conclude that VPA is a safe and effective treatment option for MDS and AML patients, particularly when used in conjunction with all-trans retinoic acid, DNA-hypomethylating drugs, and hydralazine. However, more randomized clinical studies are required to identify an ideal regimen.

The efficacy of medicinal plant preparations in the alleviation of radiodermatitis in patients with breast cancer: A systematic review of clinical trials.

Radiodermatitis in breast cancer patients varies from mild irritation to life-threatening lesions. Several studies suggest a role for topical corticosteroid ointments in the treatment of radiodermatitis. Yet, to avoid the adverse effects of corticosteroids, many authors recommend the use of topical herbal products instead. The therapeutic role of herbal treatments has yet to be fully understood. This systematic review evaluates the role of topical or oral herbal medicines in radiodermatitis prevention and treatment. A systematic search of four databases (Embase, PubMed, Web of Science, and Scopus) was performed without language and time restrictions from their inception until April 2023. The bibliographies of potential articles were also searched manually. Studies evaluated and compared the effects of herbal preparations with the control group, on dermatitis induced by radiotherapy for breast cancer. The Cochrane risk of bias tool was used to assess the included studies. Thirty-five studies were included in the systematic review. Studies which used herbal drugs including topical and oral formulations were evaluated. Herbal monotherapy and combination therapy were reported, and their effects on radiodermatitis were explained in the systematic review. In conclusion, henna ointments, silymarin gel, and Juango cream were reported to reduce the severity of radiodermatitis. These agents should be considered for radiodermatitis prophylaxis and treatment. The data on aloe gel and calendula ointment were conflicting. Further randomized controlled trials of herbal medications and new herbal formulations are required to determine their effects on breast cancer radiodermatitis.

The Effect of Adding Curcumin to Sertraline in the Treatment of Severe Major Depressive Disorder: A Randomized, Double-Blind Clinical Trial.

OBJECTIVES: Major depressive disorder (MDD) is a chronic and debilitating disease influenced by inflammatory processes in the brain. Some evidence has represented the adding curcumin as a complementary regime to the standard medication in treating depressive symptoms. However, limited clinical trials have been conducted on the antidepressants effects of curcumin in MDD patients. Therefore, this study aimed to investigate the effectiveness of curcumin in the treatment of MDD. METHODS: In a randomized, double-blind clinical trial, 45 severe MDD patients referred to the psychiatric clinic of Ibn-e-Sina Hospital, Mashhad, Iran, during 2016 were selected. Patients were randomly divided into 2 groups who received sertraline plus curcumin or placebo at a dose of 40 mg/d for 8 weeks. The patients were evaluated using Beck Anxiety and Depression Surveys at the beginning of the study, fourth, and eighth weeks by a psychiatry resident. The data analyzed aiding SPSS software. RESULTS: While depression and anxiety significantly decreased during the 8 weeks of the study, there was no significant difference between the 2 groups (P > 0.05). However, the anxiety score was lower in the intervention group. Moreover, no severe adverse events were observed in all patients. CONCLUSIONS: Adding 40 mg/d of SinaCurcumin to sertraline as a routine medical regimen did not improve the depression and anxiety levels in severe MDD patients. However, the anxiety score was lower in the intervention group than in the placebo receiver, which suggests curcumin may have a more effect on anxiety.

The importance of sleep patterns in the incidence of coronary heart disease: a 6-year prospective study in Mashhad, Iran.

Chronic shortened sleep can increase several cardiovascular risk factors, including depression, anxiety, metabolic syndrome, diabetes and hypertension. In the current study, we aimed to investigate the relationship between sleep patterns and the incidence of coronary heart disease (CHD). A total of 9704 healthy participants were recruited for the MASHAD cohort study. Within 6 years of follow-up, participants were categorized into four groups based on their number of hours of nightly sleep. Cox's proportional hazard model was used to assess relative risks (RRs) and 95% confidence intervals (CIs). During the study, 235 heart problems, including myocardial infarction, stable angina and unstable angina, were confirmed. There were significant differences between men and women who had short and long nightly sleep (p < 0.05). The incidence of CHD was significantly higher in participants with very short night sleep durations than in those with longer hours of night sleep. The subjects with very short nightly sleep were more susceptible to unstable angina (RR: 2.614 (CI 1.354-5.047)) (p < 0.05). We found that shortened nightly sleep was associated with an increased incidence of coronary heart disease in an Iranian population. These findings suggest that sleep disorders, especially shortened night sleep, can be a risk factor for CHD.

The effect of adding curcumin to sodium valproate in treatment of patients with bipolar disorder in the acute phase of mania: A randomized double-blind clinical trial.

Background: Inflammatory processes play a role in the etiopathogenesis of bipolar disorder type 1. Full therapeutic responses are seldom seen and the ongoing inflammatory processes in the brain could lead to neuronal loss. Curcumin, a relatively safe herbal compound, has been shown to have anti-inflammatory effects. The present randomized double-blind clinical trial study aimed to investigate the effect of adding curcumin to the treatment regimen of BID. Materials and methods: This randomized double-blind clinical trial was conducted on 78 patients diagnosed with BID according to the Diagnostic and Statistical Manual of Mental Disorders (DSM 5) criteria. The sample were divided into two groups. Patients in both groups received sodium valproate starting at a dose of 600 milligrams per day and administered up to 20 milligrams per kilogram per day or the highest dosage of the patient's tolerance. Patients in the intervention group also received curcumin as nanomicelle in soft gelatin capsules 40 milligrams per day. The control group received placebo tablets with the same characteristics as the curcumin tablets. They were assessed by a psychiatrist using the Young Mania Rating Scale (YMRS), Mini-Mental State Examination (MMSE), Clinical Global Impression (CGI), and a medication side effect questionnaire at the beginning of the study, as well as in the first, second, and fourth weeks of the study. Results: Among the 78 patients chosen to participate in the project, 54 people completed the trial. No specific side effect was observed in the two groups. Both groups showed an increase in their MMSE scores compared to the beginning of the study (value of p < 0.001). Although this increase was not statistically different between the two groups (value of p = 0.68). The YMRS score of both groups decreased significantly by the end of the study (value of p < 0.001); however, this decrease was not significantly different between the two groups (value of p = 0.64). In addition, the two groups experienced a significant increase in their CGI scores throughout the study (value of p < 0.001), this increase however was not statistically different between the two groups (value of p = 0.88). Conclusion: The present study suggested that curcumin may not be a useful adjuvant agent in the management of patients with BID receiving sodium valproate as treatment.Clinical trial registration: Iranian Registry of Clinical Trials (IRCT), identifier IRCT2016102530504N1.

Correlation between osteoprotegerin and coronary artery calcification in diabetic subjects: a systematic review of observational studies.

Coronary artery calcification (CAC) is one of the critical cardiovascular complications that lead to elevated morbidity and mortality among patients with type 2 diabetes (T2M). The association between osteoprotegerin (OPG) and CAC could potentially provide a reasonable chance for preventive therapy in type 2 diabetic patients and benefit the rate of mortality. Since measurement of CAC score is relatively expensive and requires radiation exposure, the current systematic review aims to provide clinical evidence for evaluating the prognostic role of OPG in determining CAC risk among subjects with T2M. Web of Science, PubMed, Embase, and Scopus, were investigated until July 2022. We assessed human studies investigating the association of OPG with CAC in type 2 diabetic patients. Quality assessment was performed by Newcastle-Ottawa quality assessment scales (NOS). Out of 459 records, 7 studies remained eligible to be included. Observational studies that provided odds ratio (OR) estimates with 95% confidence intervals (CIs) for the association between OPG and the risk of CAC were analyzed by random-effects model. In order to provide a visual summary of our findings, the estimation of pooled OR from cross-sectional studies was reported as 2.86 [95% CI 1.49-5.49], which is consistent with the findings of the cohort study. Results revealed that the association between OPG and CAC was significant among diabetic patients. OPG is hypothesized to be a potential marker in predicting the presence of high coronary calcium score among subjects with T2M that could be recognized as a novel target for further pharmacological investigations.

A pilot study of neuroprotective effect of granulocyte colony-stimulating factor (G-CSF) in patients with carbon monoxide poisoning: a double-blind, randomized, placebo-controlled trial.

Although neuroprotective effects of granulocyte colony-stimulating factor (G-CSF) have been shown in rats exposed to carbon monoxide (CO), this pilot clinical trial was performed to assess the feasibility of treatment with G-CSF in patients with acute CO poisoning. A double-blind, randomized, placebo-controlled pilot clinical trial was conducted on twenty-six patients with acute CO poisoning. G-CSF (90 µg/kg) was administered intravenously for 72 h. Demographic data, routine laboratory tests, differential blood counts, venous blood gas, and adverse reactions were recorded. The primary endpoint was brain ischemia improvement based on CT findings and the secondary endpoints examined improvements in the modified Rankin Scale (mRS), National Institutes of Health Stroke Scale (NIHSS), and Barthel Index as well as S-100ß concentrations. Fourteen patients received G-CSF, and 12 received a placebo. Twenty-six were followed for 30 days and no one in both groups died during follow-up. Neurological complications, brain ischemic changes, Barthel, and mRS were compared between the two groups on determined days after the onset of therapeutic intervention, and no significant differences were observed between the two groups. Favorable results were achieved for treated patients by different measures; NIHSS was decreased 72 h after treatment (p = 0.046), and S-100ß levels were significantly higher in the G-CSF group than in the control group, 12 h and 72 h after the treatment. G-CSF appears to have potential effects on several clinical parameters in patients with acute CO poisoning. The trial was registered at the Iranian Registry of Clinical Trials with the ID: (IRCT201607232083N7).

Hepatic Transporters Alternations Associated with Non-alcoholic Fatty Liver Disease (NAFLD): A Systematic Review.

BACKGROUND AND OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) is a progressive liver disorder and is usually accompanied by obesity, metabolic syndrome, and diabetes mellitus. NAFLD progression can lead to impaired functions of hepatocytes such as alternations in expression and function of hepatic transporters. The present study aimed to summarize and discuss the results of clinical and preclinical human studies that investigate the effect of NAFLD on hepatic transporters. METHODS: The databases of PubMed, Scopus, Embase, and Web of Science were searched systematically up to 1 March 2022. The risk of bias was assessed for cross-sectional studies through the Newcastle-Ottawa Scale score. RESULTS: Our review included ten cross-sectional studies consisting of 485 participants. Substantial alternations in hepatic transporters were seen during NAFLD progression to non-alcoholic steatohepatitis (NASH) in comparison with control groups. A significant reduction in expression and function of several hepatic uptake transporters, upregulation of many efflux transporters, downregulation of cholesterol efflux transporters, and mislocalization of canalicular transporter ABCC2 are associated with NAFLD progression. CONCLUSION: Since extensive changes in hepatic transporters could alter the pharmacokinetics of the drugs and potentially affect the safety and efficacy of drugs, close monitoring of drug administration is highly suggested in patients with NASH.

The effect of preconditioning agents on cardiotoxicity and neurotoxicity of carbon monoxide poisoning in animal studies: a systematic review.

BACKGROUND: Carbon monoxide (CO) poisoning is a common intoxication and many people die yearly due to CO poisoning and preconditioning agents attenuate brain and cardiac injury caused by intoxication. It is critical to fully understand the efficacy of new methods to directly target the toxic effect of CO, such as conditioning agents, which are currently under development. This study aims to systematically investigate current evidence from animal experiments and the effects of administration preconditions in acute and late phases after CO poisoning on cardiotoxicity and neurotoxicity. METHODS: Four databases (PubMed, Embase, Scopus, and Web of Science) were systematically searched without language restrictions, and hand searching was conducted until November 2021. We included studies that compare preconditioning agents with the control group after CO poisoning in animals. The SYRCLE RoB tool was used for risk of bias assessments. RESULTS: Thirty-seven studies were included in the study. Erythropoietin, granulocyte colony-stimulating factor (GCSF), hydrogen-rich saline, and N-butylphthalide (NBP) were found to have positive effects on reducing neurotoxicity and cardiotoxicity. As other preconditions have fewer studies, no valuable results can be deduced. Most of the studies were unclear for sources of bias. DISCUSSION: Administration of the examined preconditioning agents including NBP, hydrogen-rich saline, and GCSF in acute and late phases could attenuate neurotoxicity and cardiotoxicity of CO poisoned animals. For a better understanding of mechanisms and activities, and finding new and effective preconditioning agents, further preclinical and clinical studies should be performed to analyze the effects of preconditioning agents.

Evaluation of serum nitric oxide synthase levels in patients with coronary slow flow based on corrected TIMI frame count.

Introduction: The coronary slow flow phenomenon (CSFP) finding in angiography is characterized by the delayed filling of the terminal vessels without significant epicardial coronary disease. The endothelium performs a vital role in cardiovascular homeostasis by releasing vasoactive substances. Endothelial cells produce nitric oxide (NO) as one of these essential compounds. Three isoforms of nitric oxide synthase (NOS) are endothelial nitric oxide synthase (eNOS), neuronal nitric oxide synthase (nNOS), and induced nitric oxide synthase (iNOS). We aimed to determine the role of NOS in the development of CSFP as the first human study. Material and methods: A total of 129 patients who met the inclusion criteria were enrolled in the study. The patients were classified into five groups based on the results of coronary angiography: Group 1 without coronary artery disease (CAD) and without CSF, group 2 without CAD and with CSF, group 3 with CAD (< 50%) and without CSF, group 4 with CAD (50-90%) and without CSF, and group 5 with CAD and CSF. The serum level of NOS was determined in the participants. Coronary flow was quantified in patients with CSFP using the corrected TIMI frame count (CTFC) method, and the correlation between the levels of this biomarker and CTFC was investigated. Results: In this study, the NOS serum levels were not significantly correlated with the mean CTFC. Since the total amount of NOS was measured as a result of 3 isoforms of this enzyme, the lack of correlation could be related to increased iNOS level and decreased eNOS concentration. Conclusions: These results should be confirmed by more human studies.

Evaluation of the effect of crocin on prevention of atrial fibrillation after coronary artery bypass grafting or heart valve replacement: A double-blind, randomized, placebo-controlled trial.

Objective: The aim of this study was to evaluate the effect of crocin on the prevention of atrial fibrillation after coronary artery bypass grafting (CABG) and heart valve replacement. Materials and Methods: 100 patients who were scheduled for CABG or heart valve replacement surgeries were randomly assigned into two groups of treatment and placebo. In the treatment group, patients received crocin tablets from three days prior to surgery and on the first three postoperative days (for a total of six days). During the first three days after surgery, postoperative atrial fibrillation (POAF) was assessed by electrocardiogram monitoring. Prooxidant-antioxidant balance (PAB) and c-reactive protein (CRP) levels were also assessed. Results: POAF developed in 7 patients in the treatment group versus 18 patients in the control (p=0.02). PAB levels were significantly lower in the crocin group (p<0.001), while differences in CRP levels were insignificant (p=0.39). Conclusion: It seems that prophylactic use of crocin is effective in reducing the incidence of POAF in patients undergoing heart surgeries.

The visceral adiposity index and lipid accumulation product as predictors of cardiovascular events in normal weight subjects.

INTRODUCTION: Visceral adipose tissue (VAT) has an important role in the incidence of cardiovascular disease (CVD) than obesity by itself. The visceral adiposity index (VAI) and lipid accumulation product (LAP) are surrogate indices for measuring VAT. The aimed of this study was to investigate the association of these markers with cardiovascular events among populations with different BMI category in Mashhad, northeast of Iran. METHOD: The present study comprised a prospective cohort of 9685 men and women (35-65 years) who were recruited from MASHAD study. BMI category was defined as normal weight (BMI <25), over weight (25 ≤ BMI<30) and obese (BMI≥30). Demographic, laboratory evaluations, anthropometric and metabolic parameters were performed. Logistic and Cox regression analyses were used to determine the association and risk of cardiovascular events with VAT and LAP. RESULTS: The mean VAI and LAP in CVD patients were significantly higher than in healthy ones in all 3 groups. In terms of CVD event prediction, VAI and LAP had significant association with the incidence of CVD in the second (RR (95% CI): 2.132 (1.047-4.342) and 2.701 (1.397-5.222), respectively) and third tertiles (RR (95% CI): 2.541 (1.163-5.556) and 2.720 (1.159-6.386), respectively) in the normal group, but this association was only found in the third tertiles (RR (95% CI): 2.448 (1.205-4.971) and 2.376 (1.086-5.199), respectively) in the overweight group. The result couldn't find this association for the obese group. CONCLUSION: In this study, we found that there was a significant association between LAP and VAI and cardiovascular events in normal weight and over-weight groups; however, no significant relationship was found in the obese group.