Effect of Conditioned Medium from Human Adipose-Derived Mesenchymal Stem Cells on Human Sperm Quality During Cryopreservation.

The cryopreservation procedure decreases sperm quality, causing certain changes at structural and molecular levels affecting fertilizing ability. We aimed to investigate the impacts of human adipose-derived mesenchymal stem cells (HAd-MSCs) conditioned medium (CM) on the protection of human sperm from cryoinjury. Thirty normal semen specimens were evaluated in this study. Each specimen was separated into six groups and enhanced with varying concentrations of human Ad-MSCs-CM (0, 10, 30, 50, 70, and 100%). Sperm motility, viability, morphology, apoptosis, mitochondrial potential, and lipid peroxidation, and DNA fragmentation were evaluated before freezing and after thawing. The results showed that the total motility was preserved in 10% human Ad-MSCs-CM group. Also, DNA fragmentation was significantly lower in 10% compared to 0% human Ad-MSCs-CM (63.62 ± 17.72% vs.76.46 ± 4.87%, respectively, P < 0.004). Human Ad-MSCs-CM in groups of 10, 30, 50, and 70% reduced lipid peroxidation. The normal sperm morphology rate, mitochondrial membrane potential, and apoptosis showed no significant differences across various groups. It seems that human Ad-MSCs-CM can protect the sperm parameters during the cryopreservation by decreasing cryoinjury.

Prognostic accuracy of emergency surgery score: a systematic review.

PURPOSE: This systematic review aimed to summarize the literature regarding the prognostic accuracy of the emergency surgery score (ESS). METHOD: PubMed, Embase, Web of Science, and Scopus were comprehensively searched by May 30, 2023. Two independent researchers performed the initial screening by reviewing the titles and abstracts of the non-duplicate records and selecting the full text of articles meeting our inclusion criteria. Finally, original studies that reported the prognostic accuracy of ESS in any emergency surgeries were included. Data from the included studies were extracted into a checklist designed based on the PRISMA guidelines. The area under the curve (AUC) was used to compare the prognostic accuracy of ESS in different settings. RESULTS: Twenty-six studies met the inclusion criteria. ESS performed excellently in 30-day post-op mortality (AUC 0.84-0.89) and incidence of cardiac arrest (AUC 0.86-0.88) in emergency general surgeries. The AUC of ESS in overall 30-day morbidities varied from 0.72 to 0.82 in five cohort studies. In predicting the need for ICU admission, the study with the largest sample size reported the best sensitivity of ESS at 80% and the specificity at 85%. Moreover, an outstanding accuracy was observed for the prediction of 30-day sepsis/septic shock in emergency general surgeries (AUC 0.75-0.92). CONCLUSION: Despite the acceptable prognostic accuracy of ESS in 30-day mortality, morbidities, and in-hospital ICU admission in different emergency surgeries, the high number of required variables and the high probability of missing data highlight the need for modifications to this scoring system.

Apigenin-coated gold nanoparticles as a cardioprotective strategy against doxorubicin-induced cardiotoxicity in male rats via reducing apoptosis.

Aims: Cardiotoxicity is associated with doxorubicin (DOX), an effective anticancer drug. Apigenin has cardioprotective properties; it may be employed as a capping and reducing agent in synthesizing gold nanoparticles (AuNPs). This study examined the cardioprotective impact of AuNPs synthesized with apigenin (Api) in DOX-induced cardiotoxicity (DIC). Main methods: Api-AuNPs were synthesized in a single pot without needing additional reagents for reducing gold ions or stabilizing the NPs. The cytotoxicity of Api-AuNPs on H9c2 heart cells was subsequently determined using the MTT assay. In the animal investigation, 40 male rats were randomly assigned to one of four groups: control, cardiotoxicity (DOX), DOX treated with apigenin (DOX + Api), or DOX treated with Api-AuNPs (DOX + Api-AuNPs). To examine heart function, echocardiography was conducted. Blood samples were obtained to evaluate injury indicators (Lactate dehydrogenase (LDH), creatine kinase MB (CK-MB), Cardiac Troponin I (cTn-I), Alanine transaminase (ALT), and Aspartate transaminase (AST)). The heart was removed under general anesthetic, weighed, and preserved in formalin solution. Six micrometer-thick cardiac tissue sections were stained with hematoxylin, eosin (H&E), and immunohistochemistry to identify cardiomyocyte apoptotic markers (Bax, Bcl-2, and caspase3). Key findings: Api-AuNPs have an average size of 21.4 ± 11.6 nm and are stable in physiological environments. Api-AuNPs therapy substantially reduced body and heart weight loss compared to the DOX group. Injury indicators were reduced dramatically by Api-AuNPs treatment. Api-AuNPs inhibited myocardial apoptosis via modulating Bax, caspase3, and Bcl-2 and ameliorating tissue damage caused by DOX. Significance: Api-AuNPs' anti-apoptotic activities provide cardioprotection against DIC. It has the potential to reduce cardiotoxicity and boost myocardial performance.

In vitro effects of plasma rich in growth factors on human teratozoospermic semen samples.

There is a correlation between teratozoospermia and production of reactive oxygen species leading to poor assisted reproductive techniques outcomes. This study aimed to examine the effect of plasma-rich in growth factors (PRGF) on teratozoospermic samples. Twenty-five teratozoospermic samples were included in this study. After sperm preparation, it was divided into four groups, including 0 (control), 1, 5, and 10% PRGF. Sperm motility, viability (eosin-nigrosin staining), morphology (Papanicolaou staining), DNA fragmentation (sperm chromatin dispersion test), mitochondrial membrane potential (JC-1 staining by flow cytometry), and lipid peroxidation (measurement of malondialdehyde, MDA) were evaluated before and after 1 h of incubation with or without PRGF. Our results showed that after 1 h of incubation, the addition of 1% PRGF improved sperm progressive motility (47.72 ± 13.76%) compared to the control group (17.36 ± 8.50%) (p < 0.001). Also, 1% PRGF preserved the sperm's total motility (77.50 ± 13.28% vs. 65.63 ± 19.03%, for 1% PRGF and control, respectively) and viability after incubation. The rate of normal sperm morphology was the same between different groups. Higher mitochondrial membrane potential and lower DNA fragmentation were also observed in sperm treated with different concentrations of PRGF compared to the control group, but the differences were non-significant. The MDA levels were significantly decreased in PRGF-treated groups compared to the control group (0.99 ± 0.62, 0.95 ± 0.33, 0.95 ± 0.79, and 1.49 ± 0.27 for 1% PRGF, 5% PRGF, 10% PRGF and control, respectively). Based on our results, it seems that PRGF incubation can improve sperm parameters and especially decrease the level of malondialdehyde as an indicator of oxidative stress, which is one of the main problems of teratozoospermic samples.

Value of N-Terminal Pro-Brain Natriuretic Peptide for Embolic Events Risk Prediction in Patients with Atrial Fibrillation; a Systematic Review and Meta-Analysis.

Introduction: A comprehensive conclusion has yet to be made about the predictive value of serum N-terminal pro-brain natriuretic peptide (NT-proBNP) for stroke/systemic embolic events (SEE) in patients with atrial fibrillation (AF). This study aims to review the evidence for evaluating the value of NT-proBNP in predicting the risk of stroke/SEE in patients with AF through a systematic review and meta-analysis. Method: Two independent reviewers screened all relevant studies that were retrieved from the database of Medline, Embase, Scopus, and Web of Science until December 7th, 2021. The predictive value of NT-proBNP in the prediction of stroke/SEE was recorded as hazard ratio (HR) and 95% confidence interval (95% CI). Results: Nine articles (38,093 patients, 3.10% stroke/SEE) were included in our analysis. There was no publication bias in these studies (P=0.320). Our analysis showed that NT-proBNP can be a good predictor of stroke/SEE risk in AF patients, even at different cut-off values (HR=1.76; 95% CI: 1.51, 2.02; P < 0.001). Subgroup analysis showed that diabetes could have a possible effect on the predictive value of NT-proBNP (meta-regression coefficient = 0.042; P = 0.037). Conclusion: Measurement of NT-proBNP during the first admission could be used to assess the short- or long-term risk of stroke/SEE in patients with AF. Further studies are needed to evaluate the possible applicability of serum NT-proBNP measurement in the settings in which stroke is the sole outcome of the investigation.

Efficacy of polyarginine peptides in the treatment of stroke: A systematic review and meta-analysis.

BACKGROUND: Disparities exist regarding an efficient treatment for stroke. Polyarginines have shown promising neuroprotective properties based on available published studies. Thus, the present study aims to systemically review and analyze existing evidence regarding polyarginine's administration efficacy in animal stroke models. METHOD: Medline, Scopus, Embase, and Web of Science were systematically searched, in addition to manual search. Inclusion criteria were administrating polyarginine peptides in stroke animal models. Exclusion criteria were previous polyarginine administration, lacking a control group, review articles, and case reports. Data were collected and analyzed using STATA 17.0; a pooled standardized mean difference (SMD) with a 95% confidence interval (CI), meta-regression, and subgroup analyses were presented. Risk of bias, publication bias, and level of evidence were assessed using SYRCLE's tool, Egger's analysis, and Grading of Recommendations Assessment, Development and Evaluation framework, respectively. RESULTS: From the 468 searched articles, 11 articles were included. Analyses showed that R18 significantly decreases infarct size (SMD = -0.65; 95% CI: -1.01, -0.29) and brain edema (SMD = -1.90; 95% CI: -3.28, -0.51) and improves neurological outcome (SMD = 0.67; 95% CI: 0.44, 0.91) and functional status (SMD = 0.55; 95% CI: 0.26, 0.85) in stroke animal models. Moreover, R18D significantly decreases infarct size (SMD = -0.75; 95% CI: -1.17, -0.33) and improves neurological outcome (SMD = 0.46; 95% CI: 0.06, 0.86) and functional status (SMD = 0.35; 95% CI: 0.16, 0.54) in stroke models. CONCLUSION: Moderate level of evidence demonstrated that both R18 and R18D administration can significantly improve stroke outcomes in animal stroke models. However, considering the limitations, further pre-clinical and clinical studies are warranted to substantiate the neuroprotective efficacy of polyarginines for stroke.

The role of growth factors in human sperm parameters: A review of in vitro studies.

In vitro sperm preparation/incubation and cryopreservation are associated with oxidative stress as the main cause of sperm damage, and different strategies are used to improve sperm quality in in vitro conditions to treat male infertility. Growth factors (GFs) are biological molecules that play different roles in various cellular processes such as growth, proliferation, and differentiation. Many studies have shown that GFs and their receptors are expressed in the male reproductive system. In vitro supplementation of GFs to improve sperm parameters has yielded useful results. There are many studies on the effects of GFs on sperm quality improvement and subsequent assisted reproductive technology results. Hence, this study will review the in vitro results of various GFs including brain-derived neurotrophic factor, nerve growth factor, fibroblast growth factor, insulin-like growth factor I, and vascular endothelial growth factor to improve sperm quality.

ERK/HIF-1α/VEGF pathway: a molecular target of ELABELA (ELA) peptide for attenuating cardiac ischemia-reperfusion injury in rats by promoting angiogenesis.

BACKGROUND: Myocardial ischemia-reperfusion (I/R) injury is caused by a chain of events such as endothelial dysfunction. This study was conducted to investigate protective effects of ELABELA against myocardial I/R in Wistar rats and clarify its possible mechanisms. METHODS AND RESULTS: MI model was established based on the left anterior descending coronary artery ligation for 30 min. Then, 5 µg/kg of ELA peptide was intraperitoneally infused in rats once per day for 4 days. Western blot assay was used to assay the expression of t-ERK1/2, and p-ERK1/2 in different groups. The amount of myocardial capillary density, the expression levels of VEGF and HIF-1α were evaluated using immunohistochemistry assay. Masson's trichrome staining was utilized to assay cardiac interstitial fibrosis. The results showed that establishment of MI significantly enhanced cardiac interstitial fibrosis and changed p-ERK1/2/ t-ERK1/2 ratio. Likewise, ELA post-treatment markedly increased myocardial capillary density, the expression of several angiogenic factors (VEGF-A, HIF-1α), and reduced cardiac interstitial fibrosis by activation of ERK1/2 signaling pathways. CONCLUSION: Collectively, ELA peptide has ability to reduce myocardial I/R injury by promoting angiogenesis and reducing cardiac interstitial fibrosis through activating ERK/HIF-1α/VEGF pathway.

Doxorubicin-Induced Cardiotoxicity: An Overview on Pre-clinical Therapeutic Approaches.

Doxorubicin is an effective chemotherapeutic agent prescribed to treat solid tumors (e.g., ovary, breast, and gastrointestinal cancers). This anti-cancer drug has various side effects, such as allergic reactions, cardiac damage, hair loss, bone marrow suppression, vomiting, and bladder irritation. The most dangerous side effect of doxorubicin is cardiomyopathy, leading to congestive heart failure. The exact mechanisms of doxorubicin-induced cardiotoxicity remain incompletely understood. Alteration in myocardial structure and functional cardiac disorders is provoked by doxorubicin administration; subsequently, cardiomyopathy and congestive heart failure can occur. Congestive heart failure due to doxorubicin is associated with mortality and morbidity. Probably, doxorubicin-induced cardiotoxicity starts from myocardial cell injury and is followed by left ventricular dysfunction. Many factors and multiple pathways are responsible for the creation of doxorubicin-induced cardiotoxicity. Inflammatory cytokines, oxidative stress pathways, mitochondrial damage, intracellular Ca2+ overload, iron-free radical production, DNA, and myocyte membrane injuries have critical roles in the pathophysiology of doxorubicin-induced cardiotoxicity. Unfortunately, there are currently a few medications for the treatment of doxorubicin-induced cardiotoxicity in clinical settings. Extensive basic and clinical researches have been carried out to discover preventive treatments. This review briefly discusses the basic and experimental approaches for treating or preventing doxorubicin-mediated cardiotoxicity based on its pathophysiological mechanisms.

Nature׳s gifts to medicine: The metabolic effects of extracts from cocoons of Larinus hedenborgi (Coleoptera: Curculionidae) and their host plant Echinops cephalotes (Asteraceae) in diabetic rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Trehala manna (TM), the edible cocoons of several weevil species, e.g. Larinus hedenborgi Boheman, 1845 (Coleoptera: Curculionidae) and their host plant, i.e. Echinops cephalotes DC. (EC) (Asteraceae), are traditionally used to treat pain, inflammation, infectious diseases, as well as respiratory, renal, reproductive and metabolic disorders. AIM OF THE STUDY: This study investigated the metabolic effects of aqueous extracts from TM and EC on diabetic male Wistar albino rats. MATERIALS AND METHODS: Animals were orally gavaged with the extracts (75, 150, and 300 mg/kg), normal saline, and glibenclamide (Glbn), for 28 days. The serum levels of glucose, insulin, lipid profile, and hepatic enzymes, plus the body weight of rats were measured at the beginning and the end of study. The proximate composition of the extracts was determined, additionally. The antioxidant and cytotoxic potency of the extracts were evaluated by radical scavenging/ferric reducing and viability assays, respectively. RESULTS: Treatment of diabetic rats with the extracts significantly altered metabolic biomarkers compared with diabetic, control and Glbn-treated groups, but not in a dose-dependent manner. However, the antihyperglycemic effects of TM75/EC300, the antiobesity effects of EC150, and the hepatoprotective effects of TM150/EC150 were even stronger than those of Glbn. TM/EC-treated groups represented normal cell architecture in the pancreatic and renal tissues. Nutrient analysis displayed that TM is rich in sugar and magnesium, whereas EC is abundant in protein, sodium, potassium, and calcium. The extracts showed no antioxidant and cytotoxic effects, as compared to the control groups. CONCLUSIONS: The findings suggest that active ingredients in the extracts evaluated are responsible for the metabolic effects by lowering blood sugar and restoring the damaged islets of Langerhans. The close trophic relationship of the TM-producing beetle with the host thistle justifies the overlaps of the bioactivity of the TM and EC extracts.

Curcumin-coated gold nanoparticles attenuate doxorubicin-induced cardiotoxicity via regulating apoptosis in a mouse model.

Doxorubicin (DOX) is one of the most widely used chemotherapy agents; however, its nonselective effect causes cardiotoxicity. Curcumin (Cur), a well known dietary polyphenol, could exert a significant cardioprotective effect, but the biological application of this substance is limited by its chemical insolubility. To overcome this limitation, in this study, we synthesised gold nanoparticles based on Cur (Cur-AuNPs). Ultraviolet-visible (UV-Vis) absorbance spectroscopy and transmission electron microscopy (TEM) were performed for the characterisation of synthesised NPs, and Fourier transform infrared (FTIR) spectroscopy were applied to detect Cur on the surface of AuNPs. Its cytotoxicity effect on H9c2 cells was evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The biological efficacy of Cur-AuNPs was assessed after acute cardiotoxicity induction in BALB/c mice with DOX injection. The serum biomarkers, myocardial histological changes, and cardiomyocyte apoptosis were then measured. The results revealed that the heart protection by Cur-AuNPs is more effective than Cur alone. Heart protective effect of Cur-AuNPs was evident both in the short-term (24 hours) and long-term (14 days) study. The results of Cur-AuNPs400 after 24 hours of toxicity induction displayed the reduction of the cardiac injury serum biomarkers (LDH, CK-MB, cTnI, ADT, and ALT) and apoptotic proteins (Bax and Caspase-3), as well as increase of Bcl-2 anti-apoptotic proteins without any sign of interfibrillar haemorrhage and intercellular spaces in the heart tissue microscopic images. Our long-term study signifies that Cur-AuNPs400 in DOX-intoxicated mice could successfully inhibit body and heart weight loss in comparison to DOX group.

Will carbon nanotube/nanofiber bring new hope for the treatment of heart damage? A systematic review.

Aim: Despite scientific advances, the number of cardiovascular patients is increasing worldwide. To protect damaged cardiomyocytes from further harm, novel and safer approaches are needed to help regeneration and prevent fibrosis. Methods: In this study, we performed a systematic review of in vitro and preclinical studies of carbon nanotubes (CNTs) and carbon nanofibers (CNFs) for help to treat heart damage. Conclusion: CNTs/CNFs in hydrogels cause higher conductivity, and the in case of alignment this increase is more than the random state. CNTs/CNFs can improve structural specification of the hydrogel for cardiac cell proliferation and enhance expression of genes associated with final differentiation of various stem cells to cardiac cells.

Despite scientific advances, the number of cardiovascular patients is increasing worldwide, and unfortunately, no solution has been provided to protect patients from further damage after ischemia. The heart, unlike many tissues in the human body, lacks the ability to regenerate after damage. To protect damaged heart cells from further damage as well as to grow new heart cells, newer and safer approaches are needed to help reconstruction. In this study, we conducted a systematic review of in vitro studies and animal models of heart attack that have used carbon nanotubes and carbon nanofibers to treat heart damage. The results showed these nanomaterials increase the conductivity of the material in which they are mixed and change the structural characteristics in a way that increases the proliferation of heart cells and causes the differentiation into cardiac cells. It also helps to repair the damaged area of the heart after myocardial ischemia.

Investigating the in vitro photothermal effect of green synthesized apigenin-coated gold nanoparticle on colorectal carcinoma.

Applying toxic chemical to the synthesis of stable gold nanoparticles is one of the limitations of gold nanoparticles for therapeutic applications such as photothermal therapy. Plant compounds such as apigenin (API) with therapeutic potential can be applied in the synthesis of gold nanoparticles. API-coated gold nanoparticles (Api@AuNPs) with an average size of 19.1 nm and a surface charge of -4.3 mV have been synthesized by a simple and efficient technique. The stability of Api@AuNPs in the biological environment was verified through UV-Vis spectroscopy. Based on Raman and FTIR spectroscopy analysis, chemical binding of API on the surface of Api@AuNPs through hydroxyl and carbonyl functional groups was found to be the main reason for the stability of the Api@AuNPs in comparison with citrate-coated gold nanoparticles (Cit@AuNPs). The synthesized Api@AuNPs do not cause major toxic effects up to 128 ppm. Api@AuNP-mediated photothermal therapy leads to the indiscriminate eradication of almost half of both mouse fibroblastic (L929) and colorectal cancer (CT26) cells. Flow-cytometry analysis revealed that the cell death mechanism is mainly apoptosis. In the apoptosis triggered cell death in photothermal treatment, Api@AuNPs are preferred over commonly used gold nanoparticles in photothermal treatments which mostly trigger the necrosis cell death pathway.

Necroptosis and RhoA/ROCK pathways: molecular targets of Nesfatin-1 in cardioprotection against myocardial ischemia/reperfusion injury in a rat model.

Nesfatin-1 as a new energy-regulating peptide has been known to display a pivotal role in modulation of cardiovascular functions and protection against ischemia/reperfusion injury. However, the detailed knowledge about molecular mechanisms underlying this protection has not been completely investigated yet. This study was designed to clarify the molecular mechanisms by which nesfatin-1 exert cardioprotection effects against myocardial ischemia-reperfusion (MI/R). Left anterior descending coronary artery (LAD) was ligated for 30 min to create a MI/R model in rats. MI/R rats were treated with three concentrations of nesfatin-1 (10, 15 and 20 µg/kg) then expression of necroptosis and necrosis mediators were measured by western blotting assay. Fibrosis, morphological damages, cardiac function, myocardial injury indictors and oxidative stress factors were evaluated as well. Induction of MI/R model resulted in cardiac dysfunction, oxidative stress, increased activity of RIPK1-RIPK3-MLKL axis and RhoA/ROCK pathway, extension of fibrosis and heart tissue damage. Highest tested concentration of nesfatin-1 markedly improved cardiac function. Moreover, it reduced oxidative stress, collagen deposition, and morphological damages, through inhibiting the expression of necroptosis mediators and also, necrosis including RIPK1, RIPK3, MLKL, ROCK1, and ROCK2 proteins. The lowest and middle tested concentrations of nesfatin-1 failed to exert protective effects against MI/R. These findings have shown that nesfatin-1 can exert cardioprotection against MI/R in a dose dependent manner by suppressing necroptosis via modulation of RIPK1-RIPK3-MLKL axis and RhoA/ROCK/RIP3 signaling pathway.

Human amniotic membrane mesenchymal stem cell-conditioned medium reduces inflammatory factors and fibrosis in ovalbumin-induced asthma in mice.

NEW FINDINGS: What is the central question of this study? Is mesenchymal stem cell-conditioned medium capable of improving the pathological alterations of ovalbumin-induced asthma in mice? What is the main finding and its importance? Our study indicated that human amniotic membrane mesenchymal stem cell-conditioned medium is capable of modulating inflammation, fibrosis, oxidative stress and the pathological consequences of ovalbumin-induced allergic asthma in mice. ABSTRACT: Paracrine factors secreted by mesenchymal stem cells (MSCs) have immunomodulatory, anti-inflammatory and antifibrotic properties, and the conditioned medium (CM) of these cells might have functional capabilities. We examined the effects of human amniotic membrane MSC-CM (hAM-MSC-CM) on ovalbumin (OVA)-induced asthma. Forty male Balb/c mice were randomly divided into the following four groups: control; OVA (sensitized and challenged with OVA); OVA+CM (sensitized and challenged with OVA and treated with hAM-MSC-CM); and OVA+Placebo (sensitized and challenged with OVA and treated with placebo). Forty-eight hours after the last challenge, serum and bronchoalveolar lavage fluid samples were collected and used for evaluation of inflammatory factors and cells, respectively. Lung tissue sections were stained with Haematoxylin and Eosin or Masson's Trichrome to evaluate pathological changes, and oxidative stress was assessed in fresh lung tissues. Treatment with hAM-MSC-CM significantly hindered histopathological changes and fibrosis and reduced the total cell count and the percentage of eosinophils and neutrophils in bronchoalveolar lavage fluid. Furthermore, it reduced serum levels of immunoglobulin E, interleukin-4, transforming growth factor-ß and lung malondialdehyde. It also increased serum levels of interferon-γ and interleukin-10, in addition to the enzymatic activity of glutathione peroxidase, catalase and superoxide dismutase in lung tissue in comparison to the OVA and OVA+Placebo groups. This study showed that administration of hAM-MSC-CM can improve pathological conditions, such as inflammation, fibrosis and oxidative stress, in OVA-induced allergic asthma.

Human amniotic membrane mesenchymal stem cells-conditioned medium attenuates myocardial ischemia-reperfusion injury in rats by targeting oxidative stress.

OBJECTIVES: Ischemic heart diseases (IHD) are one of the major causes of death worldwide. Studies have shown that mesenchymal stem cells can secrete and release conditioned medium (CM) which has biological activities and can repair tissue injury. This study aimed to investigate the effects of human amniotic membrane mesenchymal stem cells (hAMCs)-CM on myocardial ischemia/reperfusion (I/R) injury in rats by targeting oxidative stress. MATERIALS AND METHODS: Male Wistar rats (40 rats, weighing 200-250 g) were randomly divided into four groups: Sham, myocardial infarction (MI), MI + culture media, and MI + conditioned medium. MI was induced by ligation of the left anterior descending coronary artery for 30 min. After 15 min of reperfusion, intramyocardial injections of hAMCs-CM or culture media (150 µl) were performed. At the end of the experiment, serum levels of cardiac troponin-I (cTn-I), myocardial levels of malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GPx), as well as cardiac histological changes were evaluated. RESULTS: HAMCs-CM significantly decreased cTn-I and MDA levels and increased SOD and GPx activities (P<0.05). In addition, hAMCs-CM improved cardiac histological changes and decreased myocardial injury percentage (P<0.05). CONCLUSION: This study showed that hAMCs-CM has cardioprotective effects in the I/R injury condition. Reduction of oxidative stress by hAMCs-CM plays a significant role in this context. Based on the results of this study, it can be concluded that hAMCs-CM can be offered as a therapeutic candidate for I/R injury in the future, but more research is needed.

Conductive carbon nanofibers incorporated into collagen bio-scaffold assists myocardial injury repair.

Currently, treatment of myocardial infarction considered as unmet clinical need. Nanomaterials have been used in the regeneration of tissues such as bone, dental and neural tissue in the body and have increased hope for revitalizing of damaged tissues. Conductive carbon base nanomaterials with its superior physicochemical properties have emerged as promising materials for cardiovascular application. In this study, we applied a biosynthetic collagen scaffold containing carbon nanofiber for regenerating of damaged heart tissue. The collagen-carbon nanofiber scaffold was fabricated and fully characterised. The scaffold was grafted on the affected area of myocardial ischemia, immediately after ligation of the left anterior descending artery in the wistar rat's model. After 4 weeks, histological analyses were performed for investigation of formation of immature cardio-myocytes, epicardial cells, and angiogenesis. Compared to untreated hearts, this scaffold significantly protects heart tissue against injury. This improvement is accompanied by a reduction in fibrosis and the increased formation of a blood vessel network and immature cardio-myocytes in the infarction heart. No toxicity detected with apoptotic and TUNEL assays. In conclusion, the mechanical support of the collagen scaffold with carbon nanofiber enhanced the regeneration of myocardial tissue.

Apigenin attenuates doxorubicin induced cardiotoxicity via reducing oxidative stress and apoptosis in male rats.

AIMS: Doxorubicin, an antibiotic belonging to anthracycline family, has been used for treatment of malignancies. Cardiotoxicity is the main adverse effect of doxorubicin. Apigenin, as a flavonoid, has antioxidant, anti-inflammatory and anti-tumoral properties. The aim of this study was the assessment of any protective effect of apigenin on cardiotoxicity induced by doxorubicin. MAIN METHODS: 40 male Wistar rats were randomly divided into 4 groups: control, cardiotoxicity (DOX), apigenin treated group (DOX + Api 25) and apigenin group (Api 25). At the end of the experiment, the markers of cardiac function (%EF, %FS, LVIDs, LVIDd), cardiac and liver injury (LDH, CK-MB, cTn-I, ALT, and AST), cardiac apoptosis (Bax, Bcl-2 and Caspase3), cardiac oxidative stress (SOD, GSH, MDA) and cardiac fibrosis were measured. KEY FINDINGS: Apigenin improved cardiac functional parameters. The levels of cardiac and liver injury markers were significantly decreased in DOX + Api 25 compared to DOX. Treatment with apigenin caused significant decrease in percentage of cardiac fibrosis in comparison with DOX. Apigenin in DOX + Api 25 group led to significant decrease in apoptotic proteins (Casp3, Bax) and a significant increase in anti-apoptotic proteins (Bcl2). In apigenin treatment groups, SOD levels significantly increased while a significant decrease was observed in MDA. The amount of GSH in DOX + Api 25 had no significant change in comparison to control and Api 25 groups. SIGNIFICANCE: Apigenin reduced cardiac injuries induced by DOX through anti-fibrotic, antioxidant and anti-apoptotic properties. It seems that apigenin prevents cardiac injuries and improves cardiac function.