The effects of citrus flavonoids supplementation on endothelial function: A systematic review and dose-response meta-analysis of randomized clinical trials.

The present systematic review and dose-response meta-analysis was conducted to synthesize existing data from randomized clinical trials (RCTs) concerning the impact of citrus flavonoids supplementation (CFS) on endothelial function. Relevant RCTs were identified through comprehensive searches of the PubMed, ISI Web of Science, and Scopus databases up to May 30, 2023. Weighted mean differences and their corresponding 95% confidence intervals (CI) were pooled utilizing a random-effects model. A total of eight eligible RCTs, comprising 596 participants, were included in the analysis. The pooled data demonstrated a statistically significant augmentation in flow-mediated vasodilation (FMD) (2.75%; 95% CI: 1.29, 4.20; I2 = 87.3%; p < 0.001) associated with CFS compared to the placebo group. Furthermore, the linear dose-response analysis indicated that each increment of 200 mg/d in CFS led to an increase of 1.09% in FMD (95% CI: 0.70, 1.48; I2 = 94.5%; p < 0.001). The findings from the nonlinear dose-response analysis also revealed a linear relationship between CFS and FMD (Pnon-linearity = 0.903, Pdose-response <0.001). Our findings suggest that CFS enhances endothelial function. However, more extensive RTCs encompassing longer intervention durations and different populations are warranted to establish more precise conclusions.

Genotoxic and cytotoxic effects of aflatoxin on the reproductive system: Focus on cell cycle dynamics and apoptosis in testicular tissue.

Aflatoxins (AFs) are inevitable environmental contaminants that are detrimental to human and animal health. AFs interfere with metabolic processes, metabolizing into different hydroxylated derivatives in the liver, as well as mechanistically induce ROS accumulation, S-phase arrest, DNA damage, and cell apoptosis. Chronic consumption of aflatoxin-contaminated foods can adversely affect the male reproductive system, cause testicular damage, prevent testosterone synthesis, decline sperm quality, and cause infertility. Oxidative stress is the fundamental pathogenesis of aflatoxin-induced reproductive toxicity. The overproduction of reactive oxygen substances can cause testicular failure and disturb the process of spermatogenesis. Mitochondria are susceptible to being impaired by oxidative stress, and its damage is associated with infertility. AFs also disturb the process of spermatogenesis by disrupting the regulation of genes related to the progression of the cell cycle such as cyclins and inducing genes related to apoptosis, thereby weakening fertility and negatively affecting the testicular endocrine potential by suppressing androgen synthesis. Additionally, AFs downregulate ERα expression, potentially negatively impacting spermatogenesis by enhancing the apoptotic mechanism. In this review, we provide new insights into the genotoxic and cytotoxic effects of AFB1 on the male reproductive system with a focus on the cell cycle and apoptosis destruction of testicular tissue.

Inpatient healthcare utilization among people with disabilities in Iran: determinants and inequality patterns.

BACKGROUND: People with disabilities (PWD) have different health service needs and different factors affect the utilization of these services. Therefore, the aim of this present study was to identify determinants of inpatient healthcare utilization among PWDs in Iran. METHODS: This research was a secondary data analysis of a cross-sectional study. The present study used data gathered for 766 PWDs (aged 18 years and older) within the Iranian Society with Disabilities (ISD) between September and December 2020. Multiple logistic regression models calculated adjusted odds ratios (aOR) and 95% confidence intervals in order to identify determinants of inpatient healthcare utilization among PWDs. RESULTS: Data for 766 people with disabilities were analyzed. A large number of participants were over 28 years of age (70.94%), male (64.36%), and single (54.02%). In the present study, more than 71% of participants had no history of hospitalization during the last year. In this study, males [aOR 2.11(1.14-3.91), participants with Civil Servants health insurance coverage [aOR 3.44 (1.16 - 10.17)] and individuals in the 3th quartile of disability severity [aOR 2.13 (1.01 - 4.51)] had greater odds of inpatient healthcare utilization compared to the other groups. The value of the concentration index (C) for inpatient healthcare utilization was - 0.084 (P.value = 0.046). The decomposition analysis indicated that gender was the greatest contributor (21.92%) to the observed inequality in inpatient healthcare utilization among participants. CONCLUSION: Our findings suggested that the likelihood of hospitalization among the study participants could be significantly influenced by factors such as gender, the health insurance scheme, and the degree of disability severity. These results underscore the imperative for enhanced access to outpatient services, affordable insurance coverage, and reduced healthcare expenditures for this vulnerable population. Addressing these issues has the potential to mitigate the burden of hospitalization and promote better health outcomes for disadvantaged individuals.

The effect of Iran's health sector evolution plan on hospitals performance indicators: an interrupted time series analysis.

Background: The Health Sector Evolution Plan (HSEP) was set up in Iran's health system to respond to some of the main problems in hospitals and other health sectors. We aimed to compare the effect of the HSEP on teaching hospital performance before and after the implementation of the HSEP through the interrupted time series (ITS) analysis. Methods: With a cross-sectional design, data collection was performed in 17 teaching hospitals affiliated with the Kermanshah University of Medical Sciences (KUMS). We used the existing data on three indicators of hospitalization rate (per 10,000 population), Emergency Department Visits (EDVs) (per 10,000 population), and in-hospital mortality (per 10,000 population). The monthly data from 2009 to 2019 was analyzed by the ITS method 60 months before and 61 months after the HSEP. Results: We found a non-statistically significant decrease in the monthly trend of hospitalization rate relative to the period before the HSEP implementation (-0.084 per 10,000 population [95%CI: -0.269, 0.101](. There was a statistically significant increase in the monthly trend of EDVs rate compared to before the HSEP implementation (1.07 per 10,000 population [95%CI: 0.14, 2.01]). Also, a significant decrease in the monthly trend of in-hospital mortality compared to before the HSEP implementation [-0.003 per 10,000 population (95%CI: -0.006, -0.001)] was observed. Conclusion: Our study demonstrated a significant increasing and decreasing trend for EDVs and in-hospital mortality following the HSEP implementation, respectively. Regarding the increase in hospitalization rate and EDVs after the implementation of HESP, it seems that there is a need to increase investment in healthcare and improve healthcare infrastructure, human resources-related indicators, and the quality of healthcare.

Synthesis, characterization and hypolipidemic effects of urazine derivatives on rat: Study of molecular modeling and enzyme inhibition.

The prevalence of hyperlipidemia has increased dramatically worldwide. It is a major public health threat, characterized by the presence of an abnormal lipid profile, primarily with elevated serum total cholesterol (TC), low-density lipoprotein (LDL), very low-density lipoprotein (VLDL) levels, and reduced high-density lipoprotein (HDL) level. Genetic factors, dietary and lifestyle habits play important roles in hyperlipidemia. It can increase the risk of chronic metabolic disorders, such as obesity, cardiovascular disease, and type II diabetes. The main objective of the present study was to evaluate the effect of urazine derivatives on serum triglyceride, cholesterol, LDL, HDL, and nitric oxide (NO) levels in high-fat diet (HFD)-induced hyperlipidemic rats. Synthetic compounds were prepared and confirmed by spectroscopic methods. Then, 88 male Sprague-Dawley rats were divided into 11 groups: control, HFD-treated group, HFD plus atorvastatin-treated group, and HFD plus 8 synthetic compounds-treated groups. The body weight, triglyceride, cholesterol, LDL, HDL, and NO levels were measured. The data with p < 0.05 were considered significant. The results indicated that HFD significantly increased cholesterol, triglyceride, and LDL levels and decreased NO concentration and HDL level compared to the control group (p < 0.05). However, HFD plus urazine derivatives significantly decreased NO, cholesterol, and triglyceride levels and increased HDL levels compared to the HFD-treated group (p < 0.05). Urazine derivatives may improve liver dysfunction in HFD-induced hyperlipidemic rats by modulation of detoxification enzymes and their anti-oxidant effects and also blood lipid profile.

Effects of collagen peptide supplementation on cardiovascular markers: a systematic review and meta-analysis of randomised, placebo-controlled trials.

Previous studies have advocated that collagen peptide supplementation (CPS) can positively affect cardiovascular health. However, the widespread impact of CPS on CVD-related markers is not fully resolved. Consequently, the current systematic review and meta-analysis aimed to assess the efficacy of CPS on CVD-related markers. A systematic search in the Scopus, PubMed and ISI Web of Science databases were completed to identify relevant randomised, placebo-controlled trials (RCT) published up to November 2021. Mean Differences were pooled using a random-effects model, while publication bias, sensitivity analyses and heterogeneity were assessed using previously validated methods. Twelve RCT, comprising of a total of eleven measured markers, were selected for the quantitative analysis. Pooled data revealed that CPS significantly decreased fat mass (-1·21 kg; 95 % CI: -2·13, -0·29; I2 = 0·0 %; P = 0·010) and increased fat-free mass, based on body mass percentage (1·49 %; 95 % CI: 0·57, 2·42; I2 = 0·0 %; P = 0·002). Moreover, collagen peptide supplementation led to a significant decrease in serum LDL (-4·09 mg/dl; 95 % CI: -8·13, -0·04; I2 = 93·4 %; P = 0·048) and systolic blood pressure (SBP) (-5·04 mmHg; 95 % CI: -9·22, -0·85; I2 = 98·9 %; P = 0·018). Our analysis also indicated that CPS did not affect glycemic markers. Our outcomes indicate that CPS reduces fat mass, LDL and SBP while increasing fat-free mass. Future investigations with longer CPS duration are needed to expand on our results.

Regenerative Medicine and Angiogenesis; Focused on Cardiovascular Disease.

Cardiovascular disease (CVD) is a major concern for health with high mortality rates around the world. CVD is often associated with partial or full occlusion of the blood vessel network. Changes in lifestyle can be useful for management early-stage disease but in the advanced stage, surgical interventions or pharmacological are needed to increase the blood flow through the affected tissue or to reduce the energy requirements. Regeneration medicine is a new science that has provided many different options for treating various diseases, especially in CVD over the years. Stem cell therapy, gene therapy, and tissue engineering are some of the powerful branches of the field that have given patients great hope in improving their condition. In this review, we attempted to examine the beneficial effects, challenges, and contradictory effects of angiogenesis in vivo, and in vitro models' studies of CVD. We hope that this information will be able to help other researchers to design new effective structures and open new avenues for the treatment of CVD with the help of angiogenesis and regeneration medicine in the future.

Polyphenols and neurodegenerative diseases: focus on neuronal regeneration.

Neurodegenerative diseases are questions that modern therapeutics can still not answer. Great milestones have been achieved regarding liver, heart, skin, kidney and other types of organ transplantations but the greatest drawback is the adequate supply of these organs. Furthermore, there are still a few options available in the treatment of neurodegenerative diseases. With great advances in medical science, many health problems faced by humans have been solved, and their quality of life is improving. Moreover, diseases that were incurable in the past have now been fully cured. Still, the area of regenerative medicine, especially concerning neuronal regeneration, is in its infancy. Presently allopathic drugs, surgical procedures, organ transplantation, stem cell therapy forms the core of regenerative therapy. However, many times, the currently used therapies cannot completely cure damaged organs and neurodegenerative diseases. The current review focuses on the concepts of regeneration, hurdles faced in the path of regenerative therapy, neurodegenerative diseases and the idea of using peptides, cytokines, tissue engineering, genetic engineering, advanced stem cell therapy, and polyphenolic phytochemicals to cure damaged tissues and neurodegenerative diseases.

An elegant technology for ultrasensitive impedimetric and voltammetric determination of cholestanol based on a novel molecularly imprinted electrochemical sensor.

In this work, a novel molecularly imprinted electrochemical sensor (MIES) has been fabricated based on electropolymerization of a molecularly imprinted polymer (MIP) onto a glassy carbon electrode (GCE) modified with gold-palladium alloy nanoparticles (AuPd NPs)/polydopamine film (PDA)/multiwalled carbon nanotubes-chitosan-ionic liquid (MWCNTs-CS-IL) for voltammetric and impedimetric determination of cholestanol (CHO). Modifications applied to the bare GCE formed an excellent biocompatible composite film which was able to selectively detect CHO molecules. Modifications applied to the bare GCE were characterized by scanning electron microscopy (SEM), cyclic voltammetry (CV) and electrochemical impedance spectroscopy (SEM). Under optimal experimental conditions, the sensor was able to detect CHO in the range of 0.1-60 pM and 1-50 pM by EIS and DPV, respectively. Moreover, the sensor showed high sensitivity, selectivity, repeatability, reproducibility, low interference and good stability towards CHO determination. Our records confirmed that the sensor was successfully able to the analysis real samples for determination of CHO.

No evidence for a major effect of three common polymorphisms of the GPx1, MnSOD, and CAT genes on PCOS susceptibility.

AIM: Polycystic ovary syndrome (PCOS) is one of the prevalent endocrine-metabolic disorders. It is proposed that oxidative stress contributes to PCOS susceptibility and its metabolic associations. The current study aimed to investigate the influence of GPx1 (rs1050450), MnSOD (rs4880), and Catalase (rs1001179) variants with PCOS susceptibility, for the first time. METHODS: In a case-control study, 350 Kurdish female volunteers (175 PCOS patients and 175 healthy controls) from Western Iran were studied. Genotyping for GPx1 and MnSOD were done using PCR-RFLP and for CAT the allele-specific PCR method was used. RESULTS: The percentage of patients suffering from hirsutism, acne, and acanthosis among patients with PCOS were 44.6%, 30.3%, and 14.9%, respectively. Distribution of alleles among patients suffering from PCOS versus healthy women was 'Pro' (69.1% vs 68.8%) and 'Leu' (31.4% vs 31.2%) for Gpx1, 'Ala' (61.43% vs 56.57%) and 'Val' (38.57% vs 43.43%) for MnSOD, and 'C' (83.43% vs 84.57%) and 'T' (16.57% vs 15.43%) for CAT. CONCLUSION: GPx1 (rs1050450), MnSOD (rs4880), and CAT (rs1001179) variants might not be a risk factor for PCOS.

Assessment of thymoquinone effects on apoptotic and oxidative damage induced by morphine in mice heart.

Opioids bind to specific receptors that are located in the central nervous system (CNS) and many other organs such as cardiovascular tissue. Morphine binds to opioid receptors and can induce oxidative stress under some certain conditions. Thymoquinone (TQ) has shown many therapeutic effects such as anti-inflammatory, antioxidant and immunomodulatory ones. Considering the oxidative effects of morphine, antioxidant effects of TQ and effects of oxidative damage in various types of biomolecules, the present study was conducted to determine the effect of morphine plus TQ on the expression of apoptotic genes in the heart of male mice. Hence we used real-time PCR to identify alterations in mRNA expression of genes involved in apoptotic pathway, including p53, Bax and Bcl-2 between the morphine-treated and TQ plus morphine-treated mice. Serum nitric oxide (NO) (Griess assay) and total antioxidant capacity (TAC) were analyzed and compared. In the morphine group, compared to control group, a significant increase in P53 and Bax mRNA expression and a significant decrease in Bcl-2 mRNA expression were observed (p < 0.01). In TQ plus morphine groups, NO was decreased (P <0 .001) and TAC levels were increased significantly (P < .001). Interestingly, TQ (9 and 18 mg/kg) plus morphine caused a significant decrease in p53 and Bax and a significant increase in Bcl2 mRNA expression, compared to morphine-treated group (p < 0.01). Collectively, the results of this study indicated that TQ, as an antioxidant, can improve the apoptotic effects induced by morphine in the heart tissue of mice.

Therapeutic effect of resveratrol on morphine-induced damage in male reproductive system of mice by reducing nitric oxide serum level / Efecto terapéutico de resveratrol sobre el daño inducido por la morfina en el sistema reproductor masculino de ratones reduciendo el nivel de óxido nítrico del suero

SUMMARY: Morphine is one of the naturally occurring phenanthrene alkaloids of opium that induces adverse effects on male reproductive system. Resveratrol is a phytoestrogen and antioxidant of red grape. The main goal is to investigate whether resveratrol could inhibit adverse effects of morphine on sperm cell viability, count, motility as well as testis histology, testosterone hormone and nitric oxide levels in mice. In the present study, 48 male rats were randomly divided into 8 groups (n=6) and were treated intraperitoneally for 14 days with normal saline, resveratrol (2, 8, 20 mg/kg/day), morphine (20 mg/kg/day) and morphine (20 mg/kg/day) + resveratrol (2, 8, 20 mg/kg/day). At the end of experiments, sperm parameters (sperm cell viability, count, motility and morphology), testis weight, the diameter of seminiferous tubules, testosterone hormone level and nitric oxide were analyzed. The data were analyzed by SPSS software for windows (version 20) using one-way ANOVA test followed by Tukey's post hoc test, and P<0.05 was considered significant. The results indicated that morphine administration significantly decreased testosterone level, count, viability and motility of sperm cells and testis weight and increased nitric oxide compared to the saline group (P=0.000). Administration of resveratrol and resveratrol plus morphine significantly increased motility, count and viability of sperm cells, somniferous tubule diameter and testosterone, while it decreased nitric oxide level compared to morphine group (P=0.025). It seems that resveratrol administration could increase the quality of spermatozoa and prevented morphine-induced adverse effects on sperm parameters.

RESUMEN: La morfina es uno de los alcaloides fenantreno del opio que induce efectos adversos en el sistema reproductivo masculino. El resveratrol es un fitoestrógeno y antioxidante de la uva roja. El objetivo principal de este trabajo fue investigar si el resveratrol puede inhibir los efectos adversos de la morfina sobre la viabilidad celular de los espermatozoides, el recuento y la motilidad, así como la histología de los testículos, la hormona testosterona y los niveles de óxido nítrico en ratones. Se dividieron, aleatoriamente, 48 ratas machos en 8 grupos (n = 6) y se trataron de forma intraperitoneal durante 14 días con solución salina normal, resveratrol (2, 8, 20 mg / kg / día), morfina (20 mg / kg / día ) y morfina (20 mg / kg / día) + resveratrol (2, 8, 20 mg / kg / día). Al final de los experimentos, se analizaron los parámetros espermáticos (viabilidad celular, recuento, motilidad y morfología), el peso de los testículos, el diámetro de los túbulos seminíferos, el nivel de la hormona testosterona y el óxido nítrico. Los datos fueron analizados con el software de SPSS para Windows (versión 20) usando una prueba de ANOVA de una vía seguida de la prueba post hoc de Tukey, y P <0,05 se consideró significativo. Los resultados indicaron que la administración de morfina disminuyó significativamente el nivel de testosterona, el recuento, la viabilidad y la motilidad de los espermatozoides y el peso de los testículos, además del aumento de óxido nítrico en comparación con el grupo salino (p = 0,000). La administración de resveratrol y resveratrol más morfina aumentó significativamente la motilidad, el recuento y la viabilidad de los espermatozoides, el diámetro de los túbulos seminíferos y la testosterona, mientras que disminuyó el nivel de óxido nítrico comparado con el grupo morfina (p = 0,025). En conclusión, la administración de resveratrol podría aumentar la calidad de los espermatozoides y prevenir los efectos adversos inducidos por la morfina sobre los parámetros espermáticos.