👤 Shadi Moradi

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social impairments, and repetitive and aggressive behaviors. The pathophysiology of ASD still remains unclear, while the population with ASD is 1/36 in children in the USA in 2024. Evidence suggests a wide range of inconsistent changes in brain-derived neurotrophic factor (BDNF), the most important neurotrophin in the central nervous system, in ASD. The present systematic review investigated studies that examined BDNF levels in three main ASD-like models in rodents [induced by valproic acid (VPA) and propionic acid (PPA), and in the BTBR mouse strain] in accord with PRISMA guidelines and in PubMed database. Forty-two studies were included. Most studies used male rats/mice. The results showed ASD model induced by VPA often leads to decreased BDNF, although unchanged or increased BDNF levels were also reported. ASD model induced by PPA leads to both increased and decreased BDNF. BDNF changes in BTBR mouse strain were also inconsistent. We found that the type of molecular assay appears to be important in evaluating BDNF. Also, few evidence showed a role for postnatal day and sex difference in BDNF changes in ASD-like rodent models. In addition, some studies have shown the potential role of the brain region in BDNF changes in different ASD-like models. In conclusion, it was suggested that inconsistencies in BDNF changes in rodent models of ASD may be related to the type of the molecular assay, the brain region, ASD model, sex, or even the postnatal day. However, evidence is still insufficient. Show less

In heart failure (HF), atherogenic dyslipidemia and lipotoxicity contribute to adverse remodeling. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) improve HF outcomes, yet their lipid effects remain debated. This review aims to synthesize quantitative changes in lipid parameters and plausible mechanisms by which SGLT2i modulate lipoproteins in HF. Across trials and HF-focused cohorts, SGLT2i are associated with small increases in low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) and small decreases in triglycerides. Beyond concentrations, emerging data suggest qualitative remodeling - a shift toward less atherogenic LDL phenotypes (small-dense LDL (sd-LDL)↓) and increases in HDL2 - although evidence is limited and heterogeneous. Mechanistically, enhanced adipose lipolysis and hepatic β-oxidation/ketogenesis may raise ketone availability for the myocardium ("thrifty substrate"), while hepatic cholesterol pool-driven LDL receptor (LDLR) downregulation could explain modest LDL-C increases. These lipid shifts coexist with consistent reductions in HF events, independent of diabetes, implying benefits not captured by traditional lipid metrics alone. In HF, SGLT2i likely exert modest quantitative lipid changes but potentially meaningful qualitative lipoprotein remodeling alongside improved metabolic flexibility. Clinically, apolipoprotein B (ApoB)-targeted therapy (e.g., statins ± ezetimibe) remains essential when LDL-C/ApoB are above goal, with SGLT2i used for cardiorenal benefit. HF-specific trials powered for ApoB, sd-LDL, low-density lipoprotein particle number (LDL-P), HDL function, and lipidomics are lacking. In conclusion, SGLT2i produce small, mixed lipid changes in HF, but mechanistic and particle-level effects may align with improved outcomes; definitive HF-centric lipid studies are a priority. Show less

Genome-wide scan for run of homozygosity (ROH) stretches, effective population size (Ne) and selection signatures can help to elucidate mechanisms of selection and pinpoint genomic regions linked with phenotypic traits. This study aimed to identify the genomic patterns of ROH, Ne and selection signatures in two Iranian main sheep breeds including Afshari and Qezel (known as meat and dairy sheep, respectively) using 49,017 single nucleotide polymorphisms (SNPs) generated using the ovine 50K SNP BeadChips. Analysis of ROH in Iranian sheep breeds revealed the differences in the pattern of ROH length and burden in these breeds. Inbreeding estimated based on ROH stretches showed very low amount of inbreeding in these indigenous sheep breeds. The Qezel breed displayed a higher Ne than Afshari breed. Furthermore, the potential selection was detected in genomic regions using three complementary approaches including FST (fixation index), XP-EHH (cross-population extended haplotype homozygosity), and hapFLK (haplotype differentiation). Our results identified the genomic regions that were enriched with the genes associated with immune response (e.g., IL23A, STAT2 and DOCK5), milk traits (e.g., PCCA, ACAP3, TTK and BTG3), energy metabolisms (e.g., GLS2), reproduction (e.g., ANGPT2), fecundity (e.g., BMP5), nervous system (e.g., DLG2, PCDH9, and FRMPD4), growth traits and muscle formation (NPY, MYF5 and PPP1R12A), and sweat gland development (SCNN1D). Some regions were also detected for the first time and overlapped with no genes suggesting novel loci associated with traits that differentiate these breeds. Overall, the finding of this study may shed light on the genomic regions linked to economically important traits in sheep as well as for developing the conservation and selection breeding programs. Show less

Neurological disorders like Alzheimer's disease (AD) and Parkinson's disease (PD) manifest through gradually deteriorating cognitive functions. An encouraging strategy for addressing these disorders involves the inhibition of precursor-cleaving enzyme 1 (BACE1). In the current research, a virtual screening technique was employed to identify potential BACE1 inhibitors among selected herbal isolates. This study evaluated 79 flavonoids, anthraquinones (AQs), and cinnamic acid derivatives for their potential blood-brain barrier (BBB) permeability. Using the AutoDock 4.0 tool, molecular docking analysis was conducted to determine the binding affinity of BBB permeable compounds to the BACE1 active site. Molecular dynamics (MD) simulations were performed to assess the stability of the docked poses of the most potent inhibitors. The interactions between the most effective plant-based inhibitors and the residues within the BACE1 catalytic site were examined before and after MD simulations. Ponciretin, danthron, chrysophanol, and N-p-coumaroyltyramine were among the highest-ranking BACE1 inhibitors, with inhibition constant values calculated in the nanomolar range. Furthermore, during 10 ns simulations, the docked poses of these ligands were observed to be stable. The findings propose that ponciretin, danthron, chrysophanol, and N-p-coumaroyltyramine might serve as potential choices for the treatment of AD and PD, laying the groundwork for the creation of innovative BACE1 inhibitors. Show less

Since obesity and diabetes are prevalent worldwide, identifying the factors affecting these two conditions can effectively alter them. We decided to investigate the expression of obesity and diabetes genes in infants with birth weights lower than 2500 g in comparison with infants with normal birth weights. 215 healthy infants between the ages of 5-6 months were used in the current case-control research, which was conducted at health and treatment facilities in Kermanshah. Infants who were healthy were chosen for the research after their weight and height were measured and compared to the WHO diagram to ensure that they were well-grown and in good health. There were 137 infants in the control group and 78 infants in the case group. All newborns had 5 cc of blood drawn intravenously. To assess the expression of the genes MC4R, MTNR1B, PTEN, ACACB, PPAR-γ, PPAR-α, NRXN3, NTRK2, PCSK1, A2BP1, TMEM18, LXR, BDNF, TCF7L2, FTO and CPT1A, blood samples were gathered in EDTA-coated vials. Chi-square, Mann-Whitney U, and Spearman analyses were used to examine the data. A significant inverse correlation between birth weight and obesity and diabetes genes, including MTNR1B, NTRK2, PCSK1, and PTEN genes (r= -0.221, -0.235, -0.246, and - 0.418, respectively). In addition, the LBW infant's expression level was significantly up-regulated than the normal-weight infants (P = 0.001, 0.007, 0.001, and < 0.001, respectively). The expression level of the PPAR-a gene had a significantly positive correlation with birth weight (r = 0.19, P = 0.005). The expression level of the PPAR-a gene in the normal-weight infants was significantly up-regulated than the LBW infants (P = 0.049). The expression levels of MTNR1B, NTRK2, PCSK1, and PTEN genes were up-regulated in the LBW infants; however, the expression level of PPAR-a gene was significantly down-regulated in the LBW infants compared to the infants with normal birth weight. Show less

Genome-wide studies related to neurological disorders and neurodegenerative diseases have pointed to the role of epigenetic changes such as DNA methylation, histone modification, and noncoding RNAs. DNA methylation machinery controls the dynamic regulation of methylation patterns in discrete brain regions. This review aims to describe the role of DNA methylation in inhibiting and progressing neurological and neurodegenerative disorders and therapeutic approaches A Systematic search of PubMed, Web of Science, and Cochrane Library was conducted for all qualified studies from 2000 to 2022. For the current need of time, we have focused on the DNA methylation role in neurological and neurodegenerative diseases and the expression of genes involved in neurodegeneration such as Alzheimer's, Depression, and Rett Syndrome. Finally, it appears that the various epigenetic changes do not occur separately and that DNA methylation and histone modification changes occur side by side and affect each other. We focused on the role of modification of DNA methylation in several genes associated with depression (NR3C1, NR3C2, CRHR1, SLC6A4, BDNF, and FKBP5), Rett syndrome (MECP2), Alzheimer's, depression (APP, BACE1, BIN1 or ANK1) and Parkinson's disease (SNCA), as well as the co-occurring modifications to histones and expression of non-coding RNAs. Understanding these epigenetic changes and their interactions will lead to better treatment strategies. This review captures the state of understanding of the epigenetics of neurological and neurodegenerative diseases. With new epigenetic mechanisms and targets undoubtedly on the horizon, pharmacological modulation and regulation of epigenetic processes in the brain holds great promise for therapy. Show less

Non-alcoholic fatty liver disease (NAFLD) is associated with a substantial increased risk of atherosclerotic cardiovascular disease (ASCVD), which is partly related to dyslipidemia and low HDL-C level. The cardioprotective activity of HDL in the body is closely connected to its role in promoting cholesterol efflux, which is determined by cholesterol efflux capacity (CEC). Hitherto, the role of HDL, as defined by CEC has not been assessed in NAFLD patients. In this research study, we present the results of a study of cAMP-treated J774 CEC and THP-1 macrophage CEC in ApoB-depleted plasma of 55 newly diagnosed NAFLD patients and 30 controls. Circulating levels of ApoA-I, ApoB, preβ-HDL, plasma activity of CETP, PLTP, LCAT and carotid intima-media thickness (cIMT) were estimated. cAMP-treated J774 and THP-1 macrophage CEC were found to be significantly lower in NAFLD patients compared to controls (P < 0.001 and P = 0.003, respectively). In addition, it was discovered that both ApoA-I and preβ1-HDL were significantly lower in NAFLD patients (P < 0.001). Furthermore, cAMP-treated J774 CEC showed independent negative correlation with cIMT, as well as the presence of atherosclerotic plaque in NAFLD patients. In conclusion, our findings showed that HDL CEC was suppressed in NAFLD patients, and impaired cAMP-treated J774 CEC was an independent risk factor for subclinical atherosclerosis in NAFLD patients, suggesting that impaired HDL functions as an independent risk factor for atherosclerosis in NAFLD. Show less