Yaser Azizi

Autism Spectrum Disorder (ASD) is characterized by difficulties in social communication, anxiety, and repetitive behaviors, and it may also be associated with cognitive memory impairment. The etiology of ASD is complex, and current treatments have limited efficacy in addressing all ASD-related symptoms. Diosgenin (Dios) has shown neuroprotective effects in various neurological conditions. This study aimed to investigate the effects of Dios on hippocampal oxidative stress, apoptosis, and behavioral outcomes in a Valproic acid (VPA) induced rat model of Autism. We examined the potential role of Dios in altering recognition memory behaviors in male rats prenatally exposed toVPA (600 mg/kg). The offspring received Dios (40 mg/kg) or Carboxymethyl cellulose (5 mg/kg) from postnatal day (PND) 23 to PND 52. Subsequently, these animals were tested with behavioral tests, including the Three-Chamber, Marble Burying, Open Field, and Passive Avoidance tests (n=8). Additionally, reactive oxygen species (ROS) markers (GSH, CAT, ROS, n=3), apoptotic markers (Caspase3, Bax, Bcl-2, n=3), and histological evaluations (Nissl staining) were performed. VPA-exposed rats displayed Autism-like behavioral impairments, including deficits in recognition memory and increased repetitive/anxiety-like behaviors. Additionally, Caspase-3 and Bax were upregulated, and Bcl2 was downregulated in hippocampal tissues. The rats in the study displayed a reduced antioxidant function, as shown by the decreased levels of GSH and CAT. Treatment with Dios mitigated markers of apoptosis and ROS, and enhanced recognition memory behavior in rats exposed to VPA. Furthermore, those treated with Dios exhibited a decrease in dark cell rates in the CA1 region of the hippocampus. This study demonstrated that markers of apoptosis and oxidative stress are elevated in rats exposed to VPA. The administration of Dios significantly reduces these markers, which in turn alleviates neuronal damage in the hippocampus and behavioral symptoms. Overall, these findings provide preclinical evidence supporting the potential neuroprotective role of Dios in an experimental model of ASD.

Background Doxorubicin (DOX) is one of the most widespread antibiotics used in the treatment of malignancies. Cardiotoxicity is the main side effect of DOX. Although the protective effects of apigenin have been shown, its mechanisms are still unknown. This study aimed to assess the role of nitric oxide (NO) in the protective effects of apigenin, particularly by altering the expression of connexin 43 (CX43) in the heart tissue. Methods and results In this study, 60 male Wistar rats were divided into six equal groups: control (normal), DOX (2 mg/kg every 48 h for 12 days i.p.), apigenin (Api, 50 mg/kg oral administration), DOX + Api, DOX + L-NAME (Nitro-L-arginine methyl ester) (30 mg/kg i.p.), and DOX + Api + L-NAME. Our study assessed alterations in the heart weight and body weight, markers of cardiac function via echocardiography Ejection Fraction (%EF), Fractional Shortening (%FS), Left Ventricular Internal Diameter in Systole (LVIDs), and Left Ventricular Internal Diameter in Diastole (LVIDd), cardiac oxidative stress factors Superoxide Dismutase (SOD), Reduced Glutathione (GSH), Malondialdehyde (MDA), Catalase (CAT), cardiac injury markers Lactate Dehydrogenase (LDH), Creatine Kinase–MB (CK-MB), and Cardiac Troponin I (cTn-I), cardiac fibrosis, and CX43 expression (immunohistochemistry). Apigenin improved cardiac tissue damage and functional parameters such as left ventricular EF. Furthermore, treatment with apigenin, but not DOX, caused a significant reduction in the percentage of cardiac fibrosis and oxidative stress activity. Apigenin can also elevate the cardiac CX43 expression in the DOX + Api compared to the DOX group. NOS inhibition by L-NAME attenuates the protective effects of apigenin in DOX-induced cardiotoxicity Cocclusion Apigenin could exert its cardioprotective effects through an NO-dependent mechanism and elevation of CX43 expression. Graphical abstract

Sodium-glucose cotransporter-2 inhibitors (SGLT2is) are a class of antidiabetic drugs that have demonstrated significant cardiovascular and renal benefits. Accumulating evidence suggests that SGLT2is also exert neuroprotective effects and may influence the progression of neurodegenerative diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS). SGLT2is modulate glucose metabolism, reduce oxidative stress, suppress inflammation, and enhance mitochondrial function. Beyond glycemic control, they show potential therapeutic effects in ameliorating the metabolic dysregulation associated with neurodegenerative pathologies. Current preclinical and clinical evidence including metabolic regulation, anti-inflammatory actions, and neuroprotective effects mediated through SGLT2is associated molecular pathways have been critically evaluated to delineate their therapeutic potential in neurodegenerative disorders. Although preclinical studies have shown promising results, more clinical trials are needed. This review highlights key research gaps and proposes future translational applications. Graphical Abstract SGLT2is mitigate neurodegeneration via anti-inflammatory, metabolic, and mitochondrial pathways.

Matrix metalloproteinases (MMPs) are a family of enzymes that play an important role in the pathophysiology of hypertensive disorders, particularly through their involvement in extracellular matrix (ECM) remodeling and vascular dysfunction. Their activity is closely linked to hypertension-mediated organ damage, which affects the vascular and cardio-renal systems. MMPs are responsible for degrading various components of the ECM, which is crucial for maintaining vascular structure and function. In hypertensive patients, several MMPs, including MMP-1, MMP-3, and MMP-9, are often found at elevated levels. This is associated with vascular remodeling and dysfunction due to chronic high blood pressure. The activation of MMPs in hypertension can be triggered by several factors, such as oxidative stress, inflammatory cytokines, and vasoactive agents like angiotensin II. In addition to increasing MMP activity, these variables cause an imbalance between MMPs and tissue inhibitors of metalloproteinases (TIMPs), which are the MMPs’ natural inhibitors. This imbalance contributes to excessive degradation of the ECM and promotes pathological changes in vascular smooth muscle cells (VSMCs), leading to their transition from a contractile to a synthetic phenotype. This shift facilitates cell growth and migration, exacerbating vascular remodeling. Given their critical roles in hypertension-related organ damage, MMPs are being explored as potential pharmacological targets. Inhibitors of MMPs may help mitigate the adverse effects of hypertension by restoring balance in ECM remodeling processes. Understanding their mechanisms opens avenues for targeted therapies that could significantly improve outcomes for individuals suffering from hypertension-related complications.

Chemotherapy is one of the routine treatment for preventing rapid growth of the tumor cells. However, chemotherapeutic agents, especially doxorubicin cause damages to the normal cells especially cardiomyocytes. Cardiotoxicity induced by chemotherapeutic drugs lead to the myocardial cell injury and finally causes left ventricular dysfunction. It seems that there were some differences in the severity of cardiovascular side effects of drugs used in the treatment of cancers. Sex hormones in male and female play crucial roles in cardiovascular development and physiological function of the heart and blood vessels. Gender differences and sex-specific hormones influence various aspects of cardiovascular health, including ventricular function, mitochondrial autophagy, and the development of abdominal aortic aneurysms. The most important gender related hormones are LH, FSH, testosterone, estrogen, progesterone, prolactin and oxytocin. They exert very important cardiovascular effects via different signaling mechanisms. Sex related hormones are also important in the cardiovascular side effects of chemotherapeutic agents, so that chronic cardiotoxicity induced by anthracyclines is more common in women. During different stages of life (before, during, and after sexual life), the levels of these hormones will be changed. This alterations can affect cardiovascular function during physiological conditions and pathological process. Because of the importance of the sex related hormones in the cardiac function, in this review we tried to comprehensively elucidate the role of these physiological hormones in cardiotoxicity induced by chemotherapeutic agents with emphasizing their signaling mechanisms.

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.

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.