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Pregnancy as a sensitive period has a critical effect on the mother and infant's life. It is well understood that dietary habits and mother awareness can improve health status and prevent pregnancy complications such as gestational diabetes, pre-eclampsia, and nausea and vomiting. The current study was conducted to investigate the association between dietary habits and self-care behaviors with pregnancy complications. This cross-sectional study was conducted across 300 pregnant women in their third trimester referred to healthcare centers and Yas hospital in Tehran, Iran. Dietary habits and self-care behaviors were assessed by valid and reliable questionnaires. Dietary intake and physical activity were evaluated using valid and reliable Food Frequency Questionnaires and Pregnancy Physical Activity questionnaires, respectively. Women with self-care behaviors had a lower rate of pre-eclampsia (P = 0.9). Regarding food habits, pregnant women who ate their meals faster had a non-significantly higher rate of gestational diabetes and pre-eclampsia. Pregnant women who consumed red meat on a daily frequency had a significantly higher rate of nausea and vomiting (OR 1.85; 95% CI 1.05-3.28, P = 0.03). Also, there was a significant positive association between the mother's pre-pregnancy BMI and gestational diabetes and pre-eclampsia [(OR 2.03; 95% CI 1.03-3.98, P = 0.03) and (OR 4.23; 95% CI 1.12-16.0, P = 0.03) respectively]. There was no significant association between pregnant women's dietary habits and GDM and pre-eclampsia. However, pregnant women with pre-pregnancy overweight and obesity had increased odds of gestational diabetes and pre-eclampsia significantly., (© 2024. The Author(s).)

Myocardial infarction (MI) is a significant cardiovascular disease that restricts blood flow, resulting in massive cell death and leading to stiff and noncontractile fibrotic scar tissue formation. Recently, sustained oxygen release in the MI area has shown regeneration ability; however, improving its therapeutic efficiency for regenerative medicine remains challenging. Here, a combinatorial strategy for cardiac repair by developing cardioprotective and oxygenating hybrid hydrogels that locally sustain the release of stromal cell-derived factor-1 alpha (SDF) and oxygen for simultaneous activation of neovascularization at the infarct area is presented. A sustained release of oxygen and SDF from injectable, mechanically robust, and tissue-adhesive silk-based hybrid hydrogels is achieved. Enhanced endothelialization under normoxia and anoxia is observed. Furthermore, there is a marked improvement in vascularization that leads to an increment in cardiomyocyte survival by ≈30% and a reduction of the fibrotic scar formation in an MI animal rodent model. Improved left ventricular systolic and diastolic functions by ≈10% and 20%, respectively, with a ≈25% higher ejection fraction on day 7 are also observed. Therefore, local delivery of therapeutic oxygenating and cardioprotective hydrogels demonstrates beneficial effects on cardiac functional recovery for reparative therapy., (© 2024 Wiley‐VCH GmbH.)

Alzheimer's disease is the most prevalent neurodegenerative disorder characterized by significant memory loss and cognitive impairments. Studies have shown that the expression level and activity of the butyrylcholinesterase enzyme increases significantly in the late stages of Alzheimer's disease, so butyrylcholinesterase can be considered as a promising therapeutic target for potential Alzheimer's treatments. In the present study, a novel series of 2,4-disubstituted quinazoline derivatives (6a-j) were synthesized and evaluated for their inhibitory activities against acetylcholinesterase (AChE) and butyrylcholinestrase (BuChE) enzymes, as well as for their antioxidant activities. The biological evaluation revealed that compounds 6f, 6h, and 6j showed potent inhibitory activities against eqBuChE, with IC 50 values of 0.52, 6.74, and 3.65 µM, respectively. These potent compounds showed high selectivity for eqBuChE over eelAChE. The kinetic study demonstrated a mixed-type inhibition pattern for both enzymes, which revealed that the potent compounds might be able to bind to both the catalytic active site and peripheral anionic site of eelAChE and eqBuChE. In addition, molecular docking studies and molecular dynamic simulations indicated that potent compounds have favorable interactions with the active sites of BuChE. The antioxidant screening showed that compounds 6b, 6c, and 6j displayed superior scavenging capabilities compared to the other compounds. The obtained results suggest that compounds 6f, 6h, and 6j are promising lead compounds for the further development of new potent and selective BuChE inhibitors., (© 2024. The Author(s).)

Objectives: Long-term video-EEG monitoring (LTM) is a new technique to assess and track fluctuations, classify seizures, identify epileptic syndromes, and determine the number of seizures and epilepsy-simulating disorders. The present study aims to evaluate the concordance of traditional EEG and LTM in assessing childhood epilepsy., Materials & Methods: This cross-sectional before-after study was performed on 120 children with epilepsy who were referred to the Epilepsy Monitoring Unit (EMU) at the Children's Medical Center between September 2021 and September 2022 and were monitored for at least eight hours in this unit. The source of the study information collection was the patients' recorded files. A neurologist reviewed the primary EEGs, and two experts blindly reviewed and interpreted the patients' LTMs under a clinical neurophysiologist's supervision., Results: The diagnoses changed after employing LTM in most children with epilepsy. Based on the diagnostic agreement analysis between EEG and LTM, the coefficient value for LTM was calculated at -0.37 (p= 0.229), showing that LTM has significantly expanded patients' diagnoses and care plans., Conclusion: The use of LTM improves the diagnosis, classification, and monitoring of epilepsy in affected children and can be a reliable supplement to EEG in some instances., Competing Interests: The authors have no conflict of interest, (© 2023 The Authors.)

Noninvasive monitoring of biofabricated tissues during the biomanufacturing process is needed to obtain reproducible, healthy, and functional tissues. Measuring the levels of biomarkers secreted from tissues is a promising strategy to understand the status of tissues during biofabrication. Continuous and real-time information from cultivated tissues enables users to achieve scalable manufacturing. Label-free biosensors are promising candidates for detecting cell secretomes since they can be noninvasive and do not require labor-intensive processes such as cell lysing. Moreover, most conventional monitoring techniques are single-use, conducted at the end of the fabrication process, and, challengingly, are not permissive to in-line and continual detection. To address these challenges, we developed a noninvasive and continual monitoring platform to evaluate the status of cells during the biofabrication process, with a particular focus on monitoring the transient processes that stem cells go through during in vitro differentiation over extended periods. We designed and evaluated a reusable electrochemical immunosensor with the capacity for detecting trace amounts of secreted osteogenic markers, such as osteopontin (OPN). The sensor has a low limit of detection (LOD), high sensitivity, and outstanding selectivity in complex biological media. We used this OPN immunosensor to continuously monitor on-chip osteogenesis of human mesenchymal stem cells (hMSCs) cultured 2D and 3D hydrogel constructs inside a microfluidic bioreactor for more than a month and were able to observe changing levels of OPN secretion during culture. The proposed platform can potentially be adopted for monitoring a variety of biological applications and further developed into a fully automated system for applications in advanced cellular biomanufacturing.

Background: To investigate the genetics of early-onset progressive cerebellar ataxia in Iran, we conducted a study at the Children's Medical Center (CMC), the primary referral center for pediatric disorders in the country, over a three-year period from 2019 to 2022. In this report, we provide the initial findings from the national registry., Methods: We selected all early-onset patients with an autosomal recessive mode of inheritance to assess their phenotype, paraclinical tests, and genotypes. The clinical data encompassed clinical features, the Scale for the Assessment and Rating of Ataxia (SARA) scores, Magnetic Resonance Imaging (MRI) results, Electrodiagnostic exams (EDX), and biomarker features. Our genetic investigations included single-gene testing, Whole Exome Sequencing (WES), and Whole Genome Sequencing (WGS)., Results: Our study enrolled 162 patients from various geographic regions of our country. Among our subpopulations, we identified known and novel pathogenic variants in 42 genes in 97 families. The overall genetic diagnostic rate was 59.9%. Notably, we observed PLA2G6, ATM, SACS, and SCA variants in 19, 14, 12, and 10 families, respectively. Remarkably, more than 59% of the cases were attributed to pathogenic variants in these genes., Conclusions: Iran, being at the crossroad of the Middle East, exhibits a highly diverse genetic etiology for autosomal recessive hereditary ataxia. In light of this heterogeneity, the development of preventive strategies and targeted molecular therapeutics becomes crucial. A national guideline for the diagnosis and management of patients with these conditions could significantly aid in advancing healthcare approaches and improving patient outcomes., (© 2024. The Author(s).)

Objective: Mitochondrial leukodystrophies (MLs) are mainly caused by impairments of the mitochondrial respiratory chains. This study reports the mutation and phenotypic spectrum of a cohort of 41 pediatric patients from 39 distinct families with MLs among 320 patients with a molecular diagnosis of leukodystrophies., Methods: This study summarizes the clinical, imaging, and molecular data of these patients for five years., Results: The three most common symptoms were neurologic regression (58.5%), pyramidal signs (58.5%), and extrapyramidal signs (43.9%). Because nuclear DNA mutations are responsible for a high percentage of pediatric MLs, whole exome sequencing was performed on all patients. In total, 39 homozygous variants were detected. Additionally, two previously reported mtDNA variants were identified with different levels of heteroplasmy in two patients. Among 41 mutant alleles, 33 (80.4%) were missense, 4 (9.8%) were frameshift (including 3 deletions and one duplication), and 4 (9.8%) were splicing mutations. Oxidative phosphorylation in 27 cases (65.8%) and mtDNA maintenance pathways in 8 patients (19.5%) were the most commonly affected mitochondrial pathways. In total, 5 novel variants in PDSS1, NDUFB9, FXBL4, SURF1, and NDUSF1 were also detected. In silico analyses showed how each novel variant may contribute to ML pathogenesis., Conclusions: The findings of this study suggest whole-exome sequencing as a strong diagnostic genetic tool to identify the causative variants in pediatric MLs. In comparison between oxidative phosphorylation (OXPHOS) and mtDNA maintenance groups, brain stem and periaqueductal gray matter (PAGM) involvement were more commonly seen in OXPHOS group (P value of 0.002 and 0.009, respectively), and thinning of corpus callosum was observed more frequently in mtDNA maintenance group (P value of 0.042)., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by high blood sugar levels. It was shown that modulating the activity of α-glucosidase, an enzyme involved in carbohydrate digestion and absorption, can improve blood sugar control and overall metabolic health in individuals with T2DM. As a result, in the current study, a series of imidazole bearing different substituted thioquinolines were designed and synthesized as α-glucosidase inhibitors. All derivatives exhibited significantly better potency (IC 50  = 12.1 ± 0.2 to 102.1 ± 4.9 µM) compared to the standard drug acarbose (IC 50  = 750.0 ± 5.0 µM). 8g as the most potent analog, indicating a competitive inhibition with K i  = 9.66 µM. Also, the most potent derivative was subjected to molecular docking and molecular dynamic simulation against α-glucosidase to determine its mode of action in the enzyme and study the complex's behavior over time. In vivo studies showed that 8g did not cause acute toxicity at 2000 mg/kg doses. Additionally, in a diabetic rat model, treatment with 8g significantly reduced fasting blood glucose levels and decreased blood glucose levels following sucrose loading compared to acarbose, a standard drug used for blood sugar control. The findings suggest that the synthesized compound 8g holds promise as an α-glucosidase inhibitor for improving blood sugar control and metabolic health., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Introduction: TPP1 variants have been identified as a causative agent of neuronal ceroid lipofuscinosis 2 disease, that ataxia is one of its clinical features. Therefore, here, molecular study of TPP1 variants is presented in an Iranian cohort and a novel pathogenic variant is described., Methods: This investigation was conducted as a cross-sectional study in a tertiary referral hospital, Children's Medical Center, Pediatrics Center of Excellence. Clinical presentations and pedigrees were documented. Patients with cerebellar ataxia were enrolled in this study. Next-generation sequencing was applied to confirm the diagnosis. Segregation and bioinformatics analyses were also done for the variants using Sanger sequencing., Results: Forty-five patients were included in our study. The mean age of onset was 104 (+55.60) months (minimum = 31 months, maximum = 216 months). The majority of cases (73.3%) were born to consanguineous parents and only 1 patient (2.2%) had an affected sibling. Of the 45 patients, only 1 patient with a novel pathogenic variant (c.1425_1425+1delinsAT, p.A476Cfs*15) in the TPP1 gene was identified., Discussion: The main strength of current study is the relatively large sample size. Besides, a novel pathogenic variant could be important toward the diagnosis and management of this condition. With significant advances in various therapies, early diagnosis could improve the treatments using personalized-based medicine., Competing Interests: The authors have no conflicts of interest to declare., (© 2023 S. Karger AG, Basel.)

Background: Leishmaniasis is a parasitic disease caused by the Leishmania protozoan affecting millions of people worldwide, especially in tropical and subtropical regions. The immune response involves the activation of various cells to eliminate the infection. Understanding the complex interplay between Leishmania and the host immune system is crucial for developing effective treatments against this disease., Methods: This study collected extensive transcriptomic data from macrophages, dendritic, and NK cells exposed to Leishmania spp. Our objective was to determine the Leishmania-responsive genes in immune system cells by applying meta-analysis and feature selection algorithms, followed by co-expression analysis., Results: As a result of meta-analysis, we discovered 703 differentially expressed genes (DEGs), primarily associated with the immune system and cellular metabolic processes. In addition, we have substantiated the significance of transcription factor families, such as bZIP and C2H2 ZF, in response to Leishmania infection. Furthermore, the feature selection techniques revealed the potential of two genes, namely G0S2 and CXCL8, as biomarkers and therapeutic targets for Leishmania infection. Lastly, our co-expression analysis has unveiled seven hub genes, including PFKFB3, DIAPH1, BSG, BIRC3, GOT2, EIF3H, and ATF3, chiefly related to signaling pathways., Conclusions: These findings provide valuable insights into the molecular mechanisms underlying the response of immune system cells to Leishmania infection and offer novel potential targets for the therapeutic goals., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Rezaei et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The design and synthesis of novel cytotoxic agents is still an interesting topic for medicinal chemistry researchers due to the unwanted side effects of anticancer drugs. In this study, a novel series of uracil-azole hybrids were designed and synthesized. The cytotoxic activity, along with computational studies: molecular docking, molecular dynamic simulation, density functional theory, and ADME properties were also, evaluated. The compounds were synthesized by using 3-methyl-6-chlorouracil as the starting material. Cytotoxicity was determined using MTT assay in the breast carcinoma cell line (MCF-7) and Hepatocellular carcinoma cell line (HEPG-2). These derivatives demonstrated powerful inhibitory activity against breast and hepatocellular carcinoma cell lines in comparison to Cisplatin as positive control. Among these compounds, 4j displayed the best selectivity profile and good activity with IC 50 values of 16.18 ± 1.02 and 7.56 ± 5.28 µM against MCF-7 and HEPG-2 cell lines respectively. Structure-activity relationships revealed that the variation in the cytotoxic potency of the synthesized compounds was affected by various substitutions of benzyl moiety. The docking output showed that 4j bind well in the active site of EGFR and formed a stable complex with the EGFR protein. DFT was used to investigate the reactivity descriptors of 4a and 4j. The outputs demonstrated that these uracil-azole hybrids can be considered as potential cytotoxic agents., (© 2023. The Author(s).)

Background: Cinnamic acid, an active compound in cinnamon spp., has anti-inflammatory and antioxidant characteristics and is favorable in managing inflammatory bowel diseases., Objectives: Evaluate cinnamic acid's effects on colitis in rats., Methods: To induce colitis in experimental rats, excluding the sham group, a 4% intrarectal solution of acetic acid was administered. The rats were then given oral doses of cinnamic acid at 30, 45, and 90 mg/kg for two days. The animals were assessed for macroscopic and microscopic changes, and the levels of inflammatory mediators such as tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and myeloperoxidase (MPO) were measured using Eliza kits. Additionally, real-time PCR was performed to examine the gene level of toll-like receptor 4 (TLR-4) in the colon., Results: Effective reduction of inflammation in acetic acid-induced colitis was achieved through Cinnamic acid administration at doses of 45 and 90 mg/kg. The decrease was achieved by inhibiting the activities of TNF-α, IL-6, and MPO while downregulating the expression of TLR-4. It is important to note that macroscopic and microscopic evaluations were significant in determining the effectiveness of cinnamic acid in reducing inflammation., Conclusion: Downregulation of inflammatory cytokines and TLR-4 expression may contribute to cinnamic acid's anti-inflammatory effect., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Introduction: Successful frozen-thawed embryo transfer (FTET) depends on multiple factors among which the woman's vaginal microbiota has recently been considered important. Using probiotic products, such as Lactovag in infertile women, the vaginal microbiome can become close to the healthy status., Objectives: The aim of this study was to evaluate the effect of Lactovag on normalizing vaginal microbiome, as well as its role in improving pregnancy outcomes in FTET cycles., Patients and Methods: This randomized blinded clinical trial was conducted on 103 patients undergoing Assisted Reproductive Technology (ART) treatment at a tertiary university-based hospital between January and August of 2019. In the experiment group, the vaginal suppository Lactavag was prescribed, whereas in the control group, patients did not receive any microbiome supplements. Then, the pregnancy rate was compared in the two groups., Results: There were no significant differences in baseline characteristics between the two study groups (p > 0.05). Positive B hCG was present in 28% (n = 26) of women, clinical pregnancy was achieved in 23.4% (n = 22) of them and fetal heart rate was detected in 21.3% (n = 20). These proportions were higher in the Lactovag group, although these differences were not significant (p > 0.05). Results showed that although transferring fetuses with grade A increased the odds of pregnancy with 1.53 (p = 0.001) folds, this ratio would be improved using Lactovag;1.68 (P value = 0.008)., Conclusions: It seems that the vaginal microbiota critically interplays with women's health and reproduction. A probiotic agent such as Lactovag can be useful in normalizing this environment and improving pregnancy outcomes in infertile women., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Leukodystrophies (LDs) are a heterogeneous group of progressive neurological disorders and characterized by primary involvement of white matter of the central nervous system (CNS). This is the first report of the Iranian LD Registry database to describe the clinical, radiological, and genomic data of Persian patients with leukodystrophies. From 2016 to 2019, patients suspicious of LDs were examined followed by a brain magnetic resonance imaging (MRI). A single gene testing or whole-exome sequencing (WES) was used depending on the neuroradiologic phenotypes. In a few cases, the diagnosis was made by metabolic studies. Based on the MRI pattern, diagnosed patients were divided into cohorts A (hypomyelinating LDs) versus cohort B (Other LDs). The most recent LD classification was utilized for classification of diagnosed patients. For novel variants, in silico analyses were performed to verify their pathogenicity. Out of 680 registered patients, 342 completed the diagnostic evaluations. In total, 245 patients met a diagnosis which in turn 24.5% were categorized in cohort A and the remaining in cohort B. Genetic tests revealed causal variants in 228 patients consisting of 213 variants in 110 genes with 78 novel variants. WES and single gene testing identified a causal variant in 65.5% and 34.5% cases, respectively. The total diagnostic rate of WES was 60.7%. Lysosomal disorders (27.3%; GM2-gangliosidosis-9.8%, MLD-6.1%, KD-4.5%), amino and organic acid disorders (17.15%; Canavan disease-4.5%, L-2-HGA-3.6%), mitochondrial leukodystrophies (12.6%), ion and water homeostasis disorders (7.3%; MLC-4.5%), peroxisomal disorders (6.5%; X-ALD-3.6%), and myelin protein disorders (3.6%; PMLD-3.6%) were the most commonly diagnosed disorders. Thirty-seven percent of cases had a pathogenic variant in nine genes (ARSA, HEXA, ASPA, MLC1, GALC, GJC2, ABCD1, L2HGDH, GCDH). This study highlights the most common types as well as the genetic heterogeneity of LDs in Iranian children., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Autosomal recessive spastic ataxia of Charlevoix Saguenay (ARSACS) is now increasingly identified from all countries over the world, possibly rendering it one of the most common autosomal recessive ataxias. Here, we selected patients harboring SACS variants, the causative gene for ARSACS, in a large cohort of 137 patients with early-onset ataxia recruited from May 2019 to May 2021 and were referred to the ataxia clinic. Genetic studies were performed for 111 out of 137 patients (81%) which led to a diagnostic rate of 72.9% (81 out of 111 cases). Ten patients with the molecular diagnosis of ARSACS were identified. We investigated the phenotypic and imaging spectra of all confirmed patients with ARSACS. We also estimated the frequency of ARSACS in this cohort and described their clinical and genetic findings including seven novel variants as well as novel neuroimaging findings. While the classic clinical triad of ARSACS is progressive cerebellar ataxia, spasticity, and sensorimotor polyneuropathy, it is not a constant feature in all patients. Sensorimotor axonal-demyelinating neuropathy was detected in all of our patients, but spasticity and extensor plantar reflex were absent in 50% (5/10). In all patients, brain magnetic resonance imaging (MRI) showed symmetric linear hypointensities in the pons (pontine stripes) and anterior superior cerebellar atrophy as well as a hyperintense rim around the thalami (thalamic rim). Although infratentorial arachnoid cyst has been reported in ARSACS earlier, we report anterior temporal arachnoid cyst in two patients for the first time, indicating that arachnoid cyst may be an associated imaging feature of ARSACS. We also extended molecular spectrum of ARSACS by presenting 8 pathogenic and one variant of unknown significance (VUS) sequence variants, which 7 of them have not been reported previously. MetaDome server confirmed that the identified VUS variant was in the intolerant regions of sacsin protein encoded by SACS., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Phospholipase-associated neurodegeneration (PLAN) caused by mutations in the PLA2G6 gene is a rare neurodegenerative disorder that presents with four sub-groups. Infantile neuroaxonal dystrophy (INAD) and PLA2G6-related dystonia-parkinsonism are the main two subtypes. In this cohort, we reviewed clinical, imaging, and genetic features of 25 adult and pediatric patients harboring variants in the PLA2G6., Methods: An extensive review of the patients' data was carried out. Infantile Neuroaxonal Dystrophy Rating Scale (INAD-RS) was used for evaluating the severity and progression of INAD patients. Whole-exome sequencing was used to determine the disease's underlying etiology followed by co-segregation analysis using Sanger sequencing. In silico prediction analysis based on the ACMG recommendation was used to assess the pathogenicity of genetic variants. We aimed to survey a genotype-genotype correlation in PLA2G6 considering all reported disease-causing variants in addition to our patients using the HGMD database and the chi-square statistical approach., Results: Eighteen cases of INAD and 7 cases of late-onset PLAN were enrolled. Among 18 patients with INAD, gross motor regression was the most common presenting symptom. Considering the INAD-RS total score, the mean rate of progression was 0.58 points per month of symptoms (Standard error 0.22, lower 95% - 1.10, and upper 95% - 0.15). Sixty percent of the maximum potential loss in the INAD-RS had occurred within 60 months of symptom onset in INAD patients. Among seven adult cases of PLAN, hypokinesia, tremor, ataxic gate, and cognitive impairment were the most frequent clinical features. Various brain imaging abnormalities were also observed in 26 imaging series of these patients with cerebellar atrophy being the most common finding in more than 50%. Twenty unique variants in 25 patients with PLAN were detected including nine novel variants. Altogether, 107 distinct disease-causing variants from 87 patient were analyzed to establish a genotype-phenotype correlation. The P value of the chi-square test did not indicate a significant relationship between age of disease onset and the distribution of reported variants on PLA2G6., Conclusion: PLAN presents with a wide spectrum of clinical symptoms from infancy to adulthood. PLAN should be considered in adult patients with parkinsonism or cognition decline. Based on the current knowledge, it is not possible to foresee the age of disease onset based on the identified genotype., (© 2023. The Author(s).)

Competing Interests: The authors declare no conflict of interest.

TbMex67 is the major mRNA export factor known to date in trypanosomes, forming part of the docking platform within the nuclear pore. To explore its role in co-transcriptional mRNA export, recently reported in Trypanosoma brucei, pulse labelling of nascent RNAs with 5-ethynyl uridine (5-EU) was performed with cells depleted of TbMex67 and complemented with a dominant-negative mutant (TbMex67-DN). RNA polymerase (Pol) II transcription was unaffected, but the procyclin loci, which encode mRNAs transcribed by Pol I from internal sites on chromosomes 6 and 10, showed increased levels of 5-EU incorporation. This was due to Pol I readthrough transcription, which proceeded beyond the procyclin and procyclin-associated genes up to the Pol II transcription start site on the opposite strand. Complementation by TbMex67-DN also increased Pol I-dependent formation of R-loops and γ-histone 2A foci. The DN mutant exhibited reduced nuclear localisation and binding to chromatin compared to wild-type TbMex67. Together with its interaction with chromatin remodelling factor TbRRM1 and Pol II, and transcription-dependent association of Pol II with nucleoporins, our findings support a role for TbMex67 in connecting transcription and export in T. brucei. In addition, TbMex67 stalls readthrough by Pol I in specific contexts, thereby limiting R-loop formation and replication stress., (© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.)

In this study, two series of novel 1,4-benzothiazine-3-one derivatives with alkyl substitution (series 1: 4a-4f) and aryl substitution (series 2: 4g-4l) were designed and synthesized based on the chemical scaffolds of perampanel, hydantoins, progabide and etifoxine as anti-convulsant agents. The chemical structures of the synthesized compounds were confirmed by FT-IR, 1 H NMR and 13 C NMR spectroscopy. Anti-convulsant effect of the compounds was examined through intraperitoneal pentylenetetrazol (i.p. PTZ) induced epilepsy mouse models. Compound 4h (4-(4-bromo-benzyl)- 4 H-benzo[b] [1,4] thiazin-3(4 H)-one) demonstrated a promising activity toward chemically-induced seizure experiment. Molecular dynamics simulation on GABA-Aergic receptors as a plausible mechanism were also done to achieve the binding and orientation of compounds in the active site of the target to evaluate the results of docking and experimental studies. The computational results were confirmed the biological activity. DFT study of 4c and 4h was performed on B3LYP/6-311 G ** level of theory. Reactivity descriptors such as HOMO, LUMO, electron affinity, ionization potential, chemical potential, hardness and softness were studied in detail and show that 4h has higher activity than 4c. Also, the frequency calculations were performed on the same level of theory and the results are in line with experimental data. Moreover, in silico ADMET properties were done to establish a relationship between the physiochemical data of the designed compounds and their in-vivo activity. Appropriate plasma protein binding and high blood-brain barrier penetration are the main features of desired in-vivo performance., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Giant axonal neuropathy (GAN) is a progressive childhood hereditary polyneuropathy that affects both the peripheral and central nervous systems. Disease-causing variants in the gigaxonin gene (GAN) cause autosomal recessive giant axonal neuropathy. Facial weakness, nystagmus, scoliosis, kinky or curly hair, pyramidal and cerebellar signs, and sensory and motor axonal neuropathy are the main symptoms of this disorder. Here, we report two novel variants in the GAN gene from two unrelated Iranian families., Methods: Clinical and imaging data of patients were recorded and evaluated, retrospectively. Whole-exome sequencing (WES) was undertaken in order to detect disease-causing variants in participants. Confirmation of a causative variant in all three patients and their parents was carried out using Sanger sequencing and segregation analysis. In addition, for comparing to our cases, we reviewed all relevant clinical data of previously published cases of GAN between the years 2013-2020., Results: Three patients from two unrelated families were included. Using WES, we identified a novel nonsense variant [NM_022041.3:c.1162del (p.Leu388Ter)], in a 7-year-old boy of family 1, and a likely pathogenic missense variant [NM_022041.3:c.370T>A (p.Phe124Ile)], in two affected siblings of the family 2. Clinical examination revealed typical features of GAN-1 in all three patients, including walking difficulties, ataxic gait, kinky hair, sensory-motor polyneuropathy, and nonspecific neuroimaging abnormalities. Review of 63 previously reported cases of GAN indicated unique kinky hair, gait problem, hyporeflexia/areflexia, and sensory impairment were the most commonly reported clinical features., Conclusions: One homozygous nonsense variant and one homozygous missense variant in the GAN gene were discovered for the first time in two unrelated Iranian families that expand the mutation spectrum of GAN. Imaging findings are nonspecific, but the electrophysiological study in addition to history is helpful to achieve the diagnosis. The molecular test confirms the diagnosis., (© 2023 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)

Toxoplasma gondii (T. gondii) is one of the most successful parasites in the world, because about a third of the world's population is seropositive for toxoplasmosis. Treatment regimens for toxoplasmosis have remained unchanged for the past 20 years, and no new drugs have been introduced to the market recently. This study, performed molecular docking to identify interactions of FDA-approved drugs with essential residues in the active site of proteins of T. gondii Dihydrofolate Reductase (TgDHFR), Prolyl-tRNA Synthetase (TgPRS), and Calcium-Dependent Protein Kinase 1 (TgCDPK1). Each protein was docked with 2100 FDA-approved drugs using AutoDock Vina. Also, the Pharmit software was used to generate pharmacophore models based on the TgDHFR complexed with TRC-2533, TgPRS in complex with halofuginone, and TgCDPK1 in complex with a bumped kinase inhibitor, RM-1-132. Molecular dynamics (MD) simulation was also performed for 100 ns to verify the stability of interaction in drug-protein complexes. Molecular Mechanics Poisson-Boltzmann Surface Area (MMPBSA) analysis evaluated the binding energy of selected complexes. Ezetimibe, Raloxifene, Sulfasalazine, Triamterene, and Zafirlukast drugs against the TgDHFR protein, Cromolyn, Cefexim, and Lactulose drugs against the TgPRS protein, and Pentaprazole, Betamethasone, and Bromocriptine drugs against TgCDPK1 protein showed the best results. These drugs had the lowest energy-based docking scores and also stable interactions based on MD analyses with TgDHFR, TgPRS, and TgCDPK1 drug targets that can be introduced as possible drugs for laboratory investigations to treat T. gondii parasite infection., (© 2023. The Author(s).)

Coordinated peri-ripple activity in the hippocampal-neocortical network is essential for mnemonic information processing in the brain. Hippocampal ripples likely serve different functions in sleep and awake states. Thus, the corresponding neocortical activity patterns may differ in important ways. We addressed this possibility by conducting voltage and glutamate wide-field imaging of the neocortex with concurrent hippocampal electrophysiology in awake mice. Contrary to our previously published sleep results, deactivation and activation were dominant in post-ripple neocortical voltage and glutamate activity, respectively, especially in the agranular retrosplenial cortex (aRSC). Additionally, the spiking activity of aRSC neurons, estimated by two-photon calcium imaging, revealed the existence of two subpopulations of excitatory neurons with opposite peri-ripple modulation patterns: one increases and the other decreases firing rate. These differences in peri-ripple spatiotemporal patterns of neocortical activity in sleep versus awake states might underlie the reported differences in the function of sleep versus awake ripples., Competing Interests: JK, ZR, TK, BM, MM No competing interests declared, (© 2023, Karimi Abadchi et al.)

Heart disease is the leading cause of death worldwide and imposes a significant burden on healthcare systems globally. A major hurdle to the development of more effective therapeutics is the reliance on animal models that fail to faithfully recapitulate human pathophysiology. The predictivity of in vitro models that lack the complexity of in vivo tissue remain poor as well. To combat these issues, researchers are developing organ-on-a-chip models of the heart that leverage the use of human induced pluripotent stem cell-derived cardiomyocytes in combination with novel platforms engineered to better recapitulate tissue- and organ-level physiology. The integration of novel biosensors into these platforms is also a critical step in the development of these models, as they allow for increased throughput, real-time and longitudinal phenotypic assessment, and improved efficiency during preclinical disease modeling and drug screening studies. These platforms hold great promise for both improving our understanding of heart disease as well as for screening potential therapeutics based on clinically relevant endpoints with better predictivity of clinical outcomes. In this review, we describe state-of-the-art heart-on-a-chip platforms, the integration of novel biosensors into these models for real-time and continual monitoring of tissue-level physiology, as well as their use for modeling heart disease and drug screening applications. We also discuss future perspectives and further advances required to enable clinical trials-on-a-chip and next-generation precision medicine platforms., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Deok-Ho Kim is a scientific founder and equity holder of Curi Bio. Deok-Ho Kim reports a relationship with Curi Bio that includes: board membership, consulting or advisory, equity or stocks, funding grants, and travel reimbursement., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Azoles are the famous and widespread scaffold in the pharmaceutical industry due to their wide range of activities, high efficacy, good tolerability, and oral availability. Furthermore, azole derivatives have attracted attention as potent antimicrobial agents., Introduction: The purpose of this review is to provide an overview of pharmacological aspects of the main scaffolds of azoles, including imidazole, benzimidazole, triazole, and tetrazole, which possess antimicrobial activity, reported from 2016 to 2020, as well as all of our publication in this field. In addition, we discuss the relationship between structure and activity and molecular docking studies of the azole derivatives to provide critical features and valuable information for the synthesis of novel azole compounds with desirable biological activities. The presented structures in this review have been tested against several bacteria and fungi, such as E. coli and C. albicans, which have been common in all of these studies., Results: A comparison of the reported MIC for tested compounds showed fluconazole base structures as the most active antifungal agents, and triazole derivatives bearing nitrophenyl and coumarin moieties to have the most dominant antibacterial activity., Conclusion: Triazole and imidazole scaffolds are more important for designing antimicrobial compounds than other azole derivatives, like benzimidazole or tetrazole. All the most active compounds were observed to fulfill the Lipinski rule., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Insufficient amounts of survival motor neuron protein is leading to one of the most disabling neuromuscular diseases, spinal muscular atrophy (SMA). Before the current study, the detailed characteristics of Iranian patients with SMA had not been determined., Objective: To describe the key demographic, clinical, and genetic characteristics of patients with SMA registered in the Iranian Registry of SMA (IRSMA)., Methods: IRSMA has been established since 2018, and the demographic, clinical, and genetic characteristics of patients with SMA were recorded according to the methods of treat neuromuscular disease (TREAT-NMD) project., Results: By October 1, 2022, 781 patients with 5q SMA were registered. Of them, 164 patients died, the majority of them had SMA type 1 and died during the first 20 months of life. The median survival of patients with type 1 SMA was 23 months. The consanguinity rate in 617 alive patients was 52.4%, while merely 24.8% of them had a positive family history. The most common type of SMA in live patients was type 3. Morbidities were defined as having scoliosis (44.1%), wheelchair dependency (36.8%), tube feeding (8.1%), and requiring mechanical ventilation (9.9%). Most of the registered patients had a homozygous deletion of SMN1, while the frequency of patients with higher copy numbers of SMN2, was less in more severe types of the disease. Earlier onset of the disease was significantly seen in patients with lower copy numbers of SMN2. The neuronal apoptosis inhibitory protein (NAIP) gene deletion was associated with a higher incidence of more severe types of SMA, higher dependency on ventilators, tube feeding, and earlier onset of the disease., Conclusions: The IRSMA is the first established Iranian nationwide registry of patients with SMA. Using this registry, decision-makers, researchers, and practitioners can precisely understand the epidemiology, characteristics, and genetics of patients with SMA in Iran.

The global spread of the coronavirus has generated one of the most critical circumstances forcing healthcare systems to deal with it everywhere in the world. The complexity of crisis management, particularly in Iran, the unfamiliarity of the disease, and a lack of expertise, provided the foundation for researchers and implementers to propose innovative solutions. One of the most important obstacles in COVID-19 crisis management is the lack of information and the need for immediate and real-time data on the situation and appropriate solutions. Such complex problems fall into the category of semi-structured problems. In this respect, decision support systems use people's mental resources with computer capabilities to improve the quality of decisions. In synergetic situations, for instance, healthcare domains cooperating with spatial solutions, coming to a decision needs logical reasoning and high-level analysis. Therefore, it is necessary to add rich semantics to different classes of involved data, find their relationships, and conceptualize the knowledge domain. For the COVID-19 case in this study, ontologies allow for querying over such established relationships to find related medical solutions based on description logic. Bringing such capabilities to a spatial decision support system (SDSS) can help with better control of the COVID-19 pandemic. Ontology-based SDSS solution has been developed in this study due to the complexity of information related to coronavirus and its geospatial aspect in the city of Tehran. According to the results, ontology can rationalize different classes and properties about the user's clinical information, various medical centers, and users' priority. Then, based on the user's requests in a web-based SDSS, the system focuses on the inference made, advises the users on choosing the most related medical center, and navigates the user on a map. The ontology's capacity for reasoning, overcoming knowledge gaps, and combining geographic and descriptive criteria to choose a medical center all contributed to promising outcomes and the satisfaction of the sample community of evaluators., Competing Interests: Conflict of interestThe authors have no competing interests to declare that are relevant to the content of this article., (© The Author(s), under exclusive licence to Springer Nature B.V. 2022. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Monkeypox is a zoonotic virus that has recently affected different countries worldwide. On July 23, 2022, the WHO declared the outbreak of monkeypox as a public health emergency of international concern. Surveillance studies conducted in Central Africa in the 1980s and later during outbreaks in the same region showed smallpox vaccines to be clinically somewhat effective against Monkeypox virus. However, there is no specific vaccine against this virus. This research used bioinformatics techniques to establish a novel multi-epitope vaccine candidate against Monkeypox that can induce a strong immune response. Five well-known antigenic proteins (E8L, A30L, A35R, A29L, and B21R) of the virus were picked and assessed as possible immunogenic peptides. Two suitable peptide candidates were selected according to bio-informatics analysis. Based upon in silico evaluation, two multi-epitope vaccine candidates (ALALAR and ALAL) were built with rich-epitope domains consisting of high-ranking T and B-cell epitopes. After predicting and evaluating the 3D structure of the protein candidates, the most efficient 3D models were considered for docking studies with Toll-like receptor 4 (TLR4) and the HLA-A * 11:01, HLA-A*01:01, HLA-A*02:01, HLA-A*03:01, HLA-A*07:02, HLA-A*15:01, HLA-A*30:01 receptors. Subsequently, molecular dynamics (MD) simulation of up to 150 nanoseconds was employed to assess the durability of the interaction of the vaccine candidates with immune receptors. MD studies showed that M5-HLA-A*11:01, ALAL-TLR4, and ALALAR-TLR4 complexes were stable during simulation. Analysis of the in silico outcomes indicates that the M5 peptide and ALAL and ALALAR proteins may be suitable vaccine candidates against the Monkeypox virus.Communicated by Ramaswamy H. Sarma.

In the current study, twenty-five indole-carbohydrazide derivatives linked to different aryl substitutions were rationally designed and synthesized. The structures of all derivatives were confirmed using different spectroscopic techniques including 1 H NMR, 13 C NMR, Mass spectrometry, and elemental analysis. The tyrosinase inhibitory activities of all synthetic compounds exhibited IC 50 values in the range of 0.070 to > 100 μM. Structure-activity relationships showed that compounds 4f (R = 4-OH, IC 50  = 0.070 μM), 8f (R = 4-OH, IC 50  = 0.072 μM), and 19e (IC 50  = 0.19 μM) with para-OH substituent at the R position was found to be the most active members of all three tested series. Kinetic studies exhibited that compounds 4f, 8f, and 19e are mixed-type inhibitors. Furthermore, toxicity and cell-based anti-melanogenesis assessments were performed on the most potent derivatives and it was shown that 4f, 8f, and 19e had no toxicity at 8 µM and reduced the percent of melanin content to 68.43, 72.61, 73.47 at 8 μM, respectively. In silico analyses of absorption, distribution, metabolism, and excretion (ADME) profile of synthesized compounds showed that these molecules followed drug-likeness rules and acceptable predictive ADMET features. Results of the docking study were almost in line with biological results with ChemPLP values of 53.56 to 79.33. Also, the docking study showed the critical interactions of potent inhibitors with the active site of the enzyme which affects the potency of the synthesized hybrids. Based on molecular dynamic simulations, compound 4f exhibited pronounced interaction with the critical residues of the tyrosinase active site so that the indole ring participated in H-bond interaction with Gly281 and 4-hydroxy benzylidene recorded another H-bond interaction with Asp289 plus hydrophobic interactions with Phe292. Hydrazide linker also exhibited three H-bond interactions with His263 and Gly281., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Herein, we reported the synthesis of nineteen novel 1,2,4-triazole derivatives including 1,3-diphenyl-2-(1H-1,2,4-triazol-1-yl) propan-1-ones (7a-e), 1-(1,3-diphenylpropan-2-yl)-1H-1,2,4-triazole (8a-c) and 1,4-diphenyl-2-(1H-1,2,4-triazol-1-yl) butane-1,4-diones (10a-k). The structures of these derivatives were confirmed by spectroscopic techniques like IR, 1 H-NMR, Mass spectroscopy and Elemental analysis. The cytotoxic activities of the synthesized compounds were evaluated against three human cancer cell lines including MCF-7, Hela and A549 using MTT assay. Compounds 7d, 7e, 10a and 10d showed a promising cytotoxic activity lower than 12 μM against Hela cell line. The safety of these compounds was also, evaluated on MRC-5 as a normal cell line and relieved that most of the synthesized compounds have proper selectivity against normal and cytotoxic cancerous cell lines. Finally, molecular docking studies were also, done to understand the mechanism and binding modes of these derivatives in the binding pocket of aromatase enzyme as a possible target., (© 2022. The Author(s).)

Non-targeted persistent immune activation or suppression by different drug delivery platforms can cause adverse and chronic physiological effects including cancer and arthritis. Therefore, non-toxic materials that do not trigger an immunogenic response during delivery are crucial for safe and effective in vivo treatment. Hydrogels are excellent candidates that can be engineered to control immune responses by modulating biomolecule release/adsorption, improving regeneration of lymphoid tissues, and enhancing function during antigen presentation. This review discusses the aspects of hydrogel-based systems used as drug delivery platforms for various diseases. A detailed investigation on different immunomodulation strategies for various delivery options and deliberate upon the outlook of such drug delivery platforms are conducted.

Background: The current study aimed to determine the seroprevalence of Toxoplasma gondii infection among HIV-positive patients and healthy subjects., Methods: This study was carried out on HIV-positive patients and healthy individuals in Southwest Iran. Five millilitres of venous blood samples were collected aseptically from each individual. Sera and buffy coats were isolated from each sample and evaluated for anti-Toxoplasma antibodies and T. gondii DNA using ELISA kit and real-time PCR, respectively. Statistical analysis was performed using SPSS 18 software., Results: Of 64 AIDS/HIV-positive patients, six (9.3%, 95% CI 7.2 to 11.3%) were seropositive for only IgG and five (7.8%, 95% CI 6.0 to 9.5%) were seropositive for both IgG and IgM. Moreover, among 64 healthy controls, 10 (15.6%, 95% CI 12.1 to 19.0%) were seropositive for only IgG and 2 (3.1%, 95% CI 2.4 to 3.7%) were seropositive for both IgG and IgM. Toxoplasma gondii DNA was detected in six samples (9.3%, 95% CI 7.2 to 11.3%) in the AIDS/HIV-positive patients group and eight samples (5.95%, 95% CI 4.6 to 7.2%) in the control group using real-time PCR. Consumption of undercooked meat was documented as an associated risk factor for T. gondii seropositivity in AIDS patients (OR 4.06, 95% CI 0.966 to 17.09; p=0.045)., Conclusions: Our findings showed a lower prevalence of Toxoplasma infection in AIDS/HIV-positive patients vs healthy controls; however, a considerable number of AIDS/HIV-positive patients were also seen to be at risk of toxoplasmosis. Based on the findings, screening and prophylaxis for toxoplasmosis should be implemented for all AIDS/HIV-positive patients in Southwest Iran., (© The Author(s) 2022. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

In the development of novel anti-α-glucosidase agents, we synthesized novel thieno[2,3-b]quinoline-hydrazones 9a-n by facile and efficient conventional chemical reactions. These compounds were characterized by IR, 1 H NMR, 13 C NMR, and elemental analysis. Inhibitory activities of the title compounds were evaluated against yeast α-glucosidase. In particular, compounds 9c, 9d, and 9h exhibited high anti-α-glucosidase activity. Representatively, compound 9c with IC 50  = 1.3 µM, was 576-times more potent than positive control acarbose. Molecular docking study of the most active compounds showed that these compounds formed important binding interactions at α-glucosidase active site. Molecular dynamics study of compound 9c was also performed and the obtained results were compared with acarbose. Compounds 9c, 9d, and 9h were also evaluated for in silico druglikeness properties and ADMET prediction. These studies showed that the title most potent compounds could be exploited as drug candidates., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: Intrauterine insemination (IUI) is the first-line treatment in couples suffering from various causes of subfertility and infertility. Considering the relatively low rate of pregnancy achieved with each cycle in this method, optimizing various steps in the process including the time interval from sperm collection to IUI may result in an increased rate of success. The goal of this study was to assess the impact of time intervals from the end of sperm processing to IUI (SP-IUI) on the pregnancy rate in IUI. Materials and methods: This single-center prospective cohort study evaluated couples with normal male partner sperm analysis and idiopathic female infertility undergoing IUI from 2018 to 2021. Cycles were stimulated using subcutaneous recombinant FSH and oral Letrozole. Ovulation was triggered using GnRH antagonist when the leading follicle's size reached greater than 14mm. The participants were placed in one of the three groups based on SP-IUI: group 1 (0-60 min), group II (60-90 min), and Group III: (>90 min). Results: 269 couples were included in the study. Sperm processing expectedly resulted in an increased concentration of total sperm count and sperm motility (P<0.001). The rate of chemical or clinical pregnancy, abortion, IUFD, multigestation, pregnancy, term birth, and ectopic pregnancy was not significantly different across study groups (P>0.05). Conclusion: The results of this study suggest that SP-IUI intervals evaluated in this study do not vary in terms of pregnancy rate or adverse pregnancy outcomes in IUI with normal male partner semen analysis. Hence, infertile couples can be flexible in the collection of semen specimens without time and site (at home or hospital) limitations., (Copyright © 2022 Tehran University of Medical Sciences. Published by Tehran University of Medical Sciences.)

In additive manufacturing, bioink formulations govern strategies to engineer 3D living tissues that mimic the complex architectures and functions of native tissues for successful tissue regeneration. Conventional 3D-printed tissues are limited in their ability to alter the fate of laden cells. Specifically, the efficient delivery of gene expression regulators (i.e. microRNAs (miRNAs)) to cells in bioprinted tissues has remained largely elusive. In this study, we explored the inclusion of extracellular vesicles (EVs), naturally occurring nanovesicles (NVs), into bioinks to resolve this challenge. EVs show excellent biocompatibility, rapid endocytosis, and low immunogenicity, which lead to the efficient delivery of miRNAs without measurable cytotoxicity. EVs were fused with liposomes to prolong and control their release by altering their physical interaction with the bioink. Hybrid EVs-liposome (hEL) NVs were embedded in gelatin-based hydrogels to create bioinks that could efficiently encapsulate and deliver miRNAs at the target site in a controlled and sustained manner. The regulation of cells' gene expression in a 3D bioprinted matrix was achieved using the hELs-laden bioink as a precursor for excellent shape fidelity and high cell viability constructs. Novel regulatory factors-loaded bioinks will expedite the translation of new bioprinting applications in the tissue engineering field., (© 2022 IOP Publishing Ltd.)

A novel series of diphenylquinoxaline-6-carbohydrazide hybrids 7a-o were rationally designed and synthesized as anti-diabetic agents. All synthesized compounds 7a-o were screened as possible α-glucosidase inhibitors and exhibited good inhibitory activity with IC 50 values in the range of 110.6 ± 6.0 to 453.0 ± 4.7 µM in comparison with acarbose as the positive control (750.0 ± 10.5 µM). An exception in this trend came back to a compound 7k with IC 50 value > 750 µM. Furthermore, the most potent derivative 7e bearing 3-fluorophenyl moiety was further explored by kinetic studies and showed the competitive type of inhibition. Additionally, the molecular docking of all derivatives was performed to get an insight into the binding mode of these derivatives within the active site of the enzyme. In silico assessments exhibited that 7e was well occupied in the binding pocket of the enzyme through favorable interactions with residues, correlating to the experimental results., (© 2022. The Author(s).)

Background: Query ID="Q1" Text="Graphical abstract: As per journal requirements, graphical abstract is necessary. Kindly check and provide the same."The magnitude of the health problems caused by leishmaniasis has been a major driving factor behind the development and implementation of leishmaniasis control programs by the national authorities in Iran, with a priority for health and environmental management. Such programs are not achievable unless all of the factors leading to the infection, including the parasite's life-cycle, vectors and reservoirs, are recognized. So far in Iran, humans and rodents have been considered the principal reservoirs of Leishmania tropica and Leishmania major, respectively, both associated with cutaneous leishmaniasis (CL), with domestic dogs considered to be the main reservoir for Leishmania infantum, associated with visceral leishmaniasis (VL). The role of other mammals in maintaining the Leishmania parasite has remained unclear. This study aimed to investigate Leishmania infection among livestock in endemic areas of VL and CL in Fars province, southern Iran, using serological and molecular methods., Methods: Blood samples from 181 clinically healthy livestock, including 49 sheep, 114 goats, 16 cattle and two donkeys, were screened to detect Leishmania DNA and anti-Leishmania antibodies using qPCR (quantitative PCR) and the direct agglutination test (DAT), respectively. Four qPCR-positive samples were amplified using the internal transcribed spacer one (ITS1) primers in conventional PCR and sent for directional sequencing., Results: Of the 181 livestock tested, 51 (28.2%) were infected with Leishmania, using serological and molecular methods. Anti-Leishmania antibodies were detected in 70 (38.7%) (95% confidence interval [CI]: 31.5-46.2) and Leishmania DNA in 93 (51.4%) (95% CI: 43.9-58.9) livestock. The identified Leishmania spp. were L. infantum and L. major., Conclusions: The findings of the present study show a relatively high prevalence of Leishmania infection among livestock in endemic areas of the disease, in Fars province, southern Iran. Given the large population of this group of animals and the fact that they live in the vicinity of the main reservoirs of the disease and vectors, it seems that sand flies regularly bite these animals. Further studies are needed to determine the role of livestock in the parasite's life-cycle and the epidemiology of Leishmania infection., (© 2022. The Author(s).)

A series of 2-aryl/alkyl-2,3-dihydro-1H-naphtho[1,2-e][1,3]oxazines (S 1 -S 11 ) were synthesized with an eco-friendly and recoverable nanocatalyst (GO-Fe 3 O 4 -Ti (IV) ) as an efficient magnetic composite. The new nanocatalyst was characterized by FT-IR, XRD and, EDS analysis. A conformable procedure, easy to work up and having a short reaction time with high yields are some advantages of this method. The new catalyst is also thermal-stable, reusable and, environment-friendly. The chemical structures of the synthesized 1,3-oxazine compounds were confirmed by comparing their melting points with those reported in literature. Then, the anticonvulsant activity of these compounds was assessed by the intraperitoneal pentylenetetrazole test (ipPTZ). Compounds S 10 and S 11 displayed considerable activity against chemically-induced seizure tests. The molecular simulation was also done to achieve their binding affinities as γ-aminobutyric acid A (GABA-A) receptor agonists as an assumptive mechanism of their anticonvulsant action. The result of molecular studies represented strongly matched with biological activity. Molecular docking simulation of the potent compound (S 10 ) and diazepam as the positive control was performed and some critical residues like Thr262, Asn265, Met286, Phe289, and Val290 were identified. Based on the anticonvulsant results and also in silico ADME predictions, S 11 can be to become a potential drug candidate as an anticonvulsant agent., (© 2022. The Author(s).)

Reduced graphene oxide (rGO) and Mg/rGO nanocomposites (NCs) were prepared by an eco-friendly technique using Rosa canina fruit extract. Physicochemical properties and cytotoxicity to Mentha longifolia in vitro cultures of these nanomaterials were examined by using XRD, FESEM, EDX, FT-IR, DLS/zeta potential, UV-Visible, and GC-MS techniques. The characterization techniques confirmed the synthesis of rGO and Mg/rGO NCs with particle sizes less than 20 nm (based on FESEM). In accordance to the biological measurements, rGO showed in vitro cytotoxicity to M. longifolia shoot cultures. Mg/rGO NCs showed no significant difference in the growth parameters except for a decrease in the shoot number at the concentrations of 50 and 150 mg/L and a decrease in the length of the tallest root at the concentrations of 100 and 150 mg/L, however efficiently improved the photosynthetic pigment contents. The phytochemical assay depicted that the total content of volatile compounds was increased in the treated cultures with 25, 50, and 100 mg/L of rGO and Mg/rGO NCs in comparison to the control. Generally, the more oxygenated and hydrocarbon sesquiterpenes were observed in the cultures treated with 25 and 100 mg/L of rGO and 25 and 50 mg/L of Mg/rGO NCs., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Coenzyme Q10 deficiency can be due to mutations in Coenzyme Q10-biosynthesis genes (primary) or genes unrelated to biosynthesis (secondary). Primary Coenzyme Q10 deficiency-4 (COQ10D4), also known as autosomal recessive spinocerebellar ataxia-9 (SCAR9), is an autosomal recessive disorder caused by mutations in the ADCK3 gene. This disorder is characterized by several clinical manifestations such as severe infantile multisystemic illness, encephalomyopathy, isolated myopathy, cerebellar ataxia, or nephrotic syndrome., Methods: In this study, whole-exome sequencing was performed in order to identify disease-causing variants in an affected girl with developmental regression and Epilepsia Partialis Continua (EPC). Next, Sanger sequencing method was used to confirm the identified variant in the patient and segregation analysis in her parents., Case Presentation: The proband is an affected 11-year-old girl with persistent seizures, EPC, and developmental regression including motor, cognition, and speech. Seizures were not controlled with various anticonvulsant drugs despite adequate dosing. Progressive cerebellar atrophy, stroke-like cortical involvement, multifocal hyperintense bright objects, and restriction in diffusion-weighted imaging (DWI) were seen in the brain magnetic resonance imaging (MRI)., Conclusions: A novel homozygous missense variant [NM&#95;020247.5: c.814G>T; (p.Gly272Cys)] was identified within the ADCK3 gene, which is the first mutation in this gene in the Iranian population. Bioinformatics analysis showed this variant is damaging. Based on our patient, clinicians should consider genetic testing earlier to instant diagnosis and satisfactory treatment based on exact etiology to prevent further neurologic sequelae., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

To evaluate the diagnostic performance of five alternative serodiagnostic tests, serum samples from 100 confirmed visceral leishmaniasis (VL) patients, 197 healthy endemic individuals, and 58 non-VL patients living in southern Iran were compared. The VL patients were defined as individuals with a positive result of the immunofluorescent antibody test (IFAT), having clinical signs and symptoms and appropriate response to treatment. The index tests were two direct agglutination tests, DAT-ITM (Institute of Tropical Medicine, Antwerp, Belgium) and DAT-KIT (Royal Tropical Institute, Amsterdam, The Netherlands), and three rapid diagnostic tests (RDTs), Kalazar Detect (InBios International Inc., USA), IT Leish (Bio-Rad, catalog 710124), and Leishmania test (Cypress Diagnostic Company, Belgium). Sensitivities of DAT-ITM and DAT-KIT were low, respectively, 56% and 59%, while specificities were acceptable, respectively, 98% and 93%. Observed sensitivities and specificities of RDTs were higher (71%, 81%, 70% and 99%, 99%, 98% for Kalazar Detect, IT Leish, and Leishmania test, respectively). Even with a maximum sensitivity of 81%, RDTs missed almost one-fifth of VL patients that were positive in IFAT. We conclude that RDTs in VL patients do not possess adequate performance in southern Iran and require some improvement, but they can still be helpful in the diagnosis and screening of the disease in this region due to their high specificity and speed., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Zahra Rezaei et al.)

The present study aims to investigate the changes in different parameters related to the storage time of red blood cell (RBC) units. Microscopic, flow cytometric, and electrophoretic assessments were employed every few days for 60 days to investigate the alterations in morphology, size, phosphatidylserine (PS) externalization, and membrane proteins over time. Morphological transformation from discocytes to spherocytes progressed as the storage time increased, which was accompanied by an increment of cellular size. However, this storage period did not result in the externalization of significant amounts of PS ( p  > 0.05). Mean Fluorescence Intensity (MFI) values increased by 11% to 23% between days 21 and 35 compared to the day 1 sample ( p  < 0.001). By day 60, the MFI decreased to about 70% of the day 1 sample. The analysis of membrane proteins' distribution showed a significant drop in band 3 expression after 35 days ( p  < 0.05 and 0.001 on days 42 and 60, respectively); however, no significant change was observed up to five weeks ( p  > 0.05). The inconsistency observed between Eosin-5-Maleimide (5-EMA) binding and the relative band 3 content could be due to additional accessibility of 5-EMA to hidden domains of other membrane proteins on RBCs as a result of increased mean corpuscular volume (MCV) and changes in morphology. Overall, our present study represents a step-wise and time-dependent series of events that progressively affects stored RBCs., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© Indian Society of Hematology and Blood Transfusion 2021.)

In the present study, to evaluate the role of the basolateral amygdala (BLA) in morphine addiction, the BLA was stimulated electrically, or inactivated temporarily using lidocaine. The electrical stimulation (ES) was delivered to BLA with low or high intensities (LI or HI: 25 or 150 µA, respectively), and five minutes before morphine administration with effective or ineffective doses, lidocaine was microinjected into the BLA. Using a 5-day conditioned place preference (CPP) paradigm, the dependence on morphine was evaluated. The results showed that LI-ES of BLA induced CPP in both the acquisition and expression phases, in the control and the ineffective dose of morphine groups. HI-ES had no effect on CPP acquisition but induced aversion in the expression, with both effective and ineffective doses of morphine. Inactivation of BLA using lidocaine, inhibited morphine-induced CPP in both acquisition and expression phases. The results of the present study indicate the prominent role of BLA in morphine addiction and dependence. Considering the contradictory results of different intensities of ES, it can be inferred that there are different neural circuits in this area of the brain, in relation to the reward responses., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: In the present study, the effects of intra-basolateral amygdala (BLA) blockade of dopamine D1 receptor on morphine-induced conditioned place preference (CPP) were investigated in male Wistar rats., Materials and Methods: A 5-day CPP paradigm was used. Morphine was injected subsequently at effective (5 mg/kg) and ineffective (0.5 mg/kg) doses. SCH 23390 (0.5- μg/rat), as a selective D1 receptor antagonist, was microinjected bilaterally into the BLA., Results: Effective dose of morphine induced a significant CPP, and increased the locomotor activity during the testing phase. The results showed that morphine-induced CPP was significantly suppressed by D1 receptors antagonist in BLA in the acquisition phase and caused an aversion even at high doses. The antagonist also significantly prevented CPP expression. Morphine increased the motor activity, but the D1 receptors blockade, significantly reduced it., Conclusions: The findings of this study suggest a possible role for BLA dopamine D1 receptors in reward responses in morphine dependency., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Advanced Biomedical Research.)

Background: Blastocystis sp., located in the large intestine, is one of the most common zoonotic parasites. Risk factors affect its prevalence and pathogenicity, and it causes gastrointestinal disorders. Thus, this study aimed to investigate the Blastocystis sp. prevalence and its relationship with gastrointestinal disorders, in patients referred to laboratories, and provide some prevention strategies., Methods: In this descriptive-analytical study, 1,000 stool specimens were collected from patients referred to Ilam, Iran laboratories from 2018-2019. Wet mount method was conducted on samples, and suspected specimens were confirmed using trichrome staining. The demographic and clinical information was recorded in a questionnaire. Finally, the results were analyzed using the SPSS., Results: Blastocystis infection was detected in 81 out of 1,000 patients (8.1%) including 61 (75.3%) males and 20 (24.7%) females. and illiterate people were more at risk. The prevalence in rural was more than urban areas, and it was more in the age group of 31-50 year., Conclusion: There was a significant relationship between Blastocystis sp. and risk factors (age, sex, level of education, and residence) and clinical symptoms (stomach ache and nausea) ( P <0.05), but interestingly there was no significant relationship between bloating and diarrhea., Competing Interests: Conflict of interest The authors have no conflicts of interest to declare., (Copyright © 2022 Viesy et al. Published by Tehran University of Medical Sciences.)

Background: Tubulin inhibitors have proved to be a promising treatment against cancer. Tubulin inhibitors target different areas in microtubule structure to exert their effects. The colchicine binding site (CBS) is one of them for which there is no FDA-approved drug yet. This makes CBS a desirable target for drug design., Methods: Primary virtual screening is done by developing a possible pharmacophore model of colchicine binding site inhibitors of tubulins, and 2,3-diphenylquinoxaline is chosen as a lead compound to synthesis. In this study, 28 derivatives of 2,3-diphenylquinoxalines are synthesized, and their cytotoxicity is evaluated by the MTT assay in different human cancer cell lines, including AGS (Adenocarcinoma gastric cell line), HT-29 (Human colorectal adenocarcinoma cell line), NIH3T3 (Fibroblast cell line), and MCF-7 (Human breast cancer cell)., Results: Furthermore, the activity of the studied compounds was investigated using computational methods involving molecular docking of the 2,3-diphenylquinoxaline derivatives to β-tubulin. The results showed that the compounds with electron donor functionalities in positions 2 and 3 and electron-withdrawing groups in position 6 are the most active tubulin inhibitors., Conclusion: Apart from the high activity of the synthesized compounds, the advantage of this report is the ease of the synthesis, work-up, and isolation of the products in safe, effective, and high-quality isolated yields., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background. Toxoplasma gondii is an intracellular protozoan parasite responsible for systemic disease in a wide range of warm-blooded animals. The current study is aimed at evaluating the prevalence of Toxoplasma infection in dogs, using serological and molecular methods in rural areas in Kazeroun Township, Fars province, southern Iran. Methods. Blood samples were obtained from 60 clinically healthy dogs with an age range of 1 to 7 years in three rural areas of Fars province, southern Iran. Sera and buffy coats were used to assess the T. gondii infection using both modified agglutination test (MAT) and real-time PCR. Results . Antibodies against T. gondii were detected in 5 out of 60 (8.3%) dogs by the MAT method, and T. gondii DNA was detected in 17 out of 60 (28.3%) studied animals. There was no significant association between sex and seropositivity to Toxoplasma ( p > 0.05). Fair agreement (kappa = 0.27) was seen between molecular and serological findings where three dogs with positive serological results had a positive molecular test. Conclusion. Findings of the present study show a relatively high prevalence of T. gondii infection in dogs in rural areas in Fars province, southern Iran. Finding the parasite genotype in dogs deserves further study., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Zahra Rezaei et al.)