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Abstract The use of drug delivery systems in targeting and achieving the targeting of drugs in treating diseases, especially cancer, has attracted the attention of researchers. Letrozole is one of the drugs for the treatment of breast cancer. In this study, the organic-metallic pharmaceutical porous nanostructure based on zirconium UiO-66 loaded letrozole was synthesized. Its cytotoxicity and effect on apoptosis and migration against breast cancer cell line were investigated. In this experimental study, the UiO-66 nanoparticle-loaded letrozole was synthesized using zirconium chloride (ZrCl4), dimethylformamide (DMF), and HCl. Its characteristics were determined by scanning electron microscopy, and its average size was determined by the DLS method. Also, the rate of letrozole drug release from the nanoparticle was investigated in 24, 48, and 72 h. In addition, its cytotoxicity effects were investigated using the MTT colorimetric method at concentrations of 3.125-100 µg/ml against the breast cancer cell line (MCF-7) in the periods of 48 and 72 h. Also, the expression level of apoptotic genes Bax and Bcl2 was investigated by the Real-Time PCR method. Also, the amount of cell migration was done by the migration assay method. The results showed that UiO-66 bound to letrozole had a spherical morphology and an average size of 9.2 ± 160.1. Also, the letrozole drug was loaded by 62.21 ± 1.80% in UiO-66 nanoparticles and had a slower release pattern than free letrozole in the drug release test, so within 72 h, 99.99% of free letrozole was released in If in UiO-66 containing letrozole, 57.55% of the drug has been released. Also, the cytotoxicity results showed that UiO-66 bound to letrozole has more significant cytotoxic effects than free letrozole (p

Human leukocyte antigen G (HLA-G) levels are among the biomarkers suggested for pre-eclampsia (PE). This studyis aimed at determining the possible relationship between low soluble HLA-G (sHLA-G) levels in maternal blood atthe beginning of pregnancy and subsequent PE. We searched the international scientific databases of Web of Science,Embase, PubMed, Cochrane, and Scopus. We extracted the studies investigating the relationship between the serumlevels of HLA-G in the first trimester of pregnancy and the onset of PE using the appropriate keywords. The collecteddata were analyzed using the random-effects meta-analysis model and STATA (version 14). A total of 5 studies metthe eligibility criteria, and the total sample size was 668 subjects. The mean and SD age of case subjects was 31.41 ±4.16 years, while it was 30.56 ± 3.5 for control subjects. According to the findings, there was an inverse relationshipbetween HLA-G serum level in the first trimester of pregnancy and the subsequent onset of PE, standard mean difference(SMD)=-1.51 [95% confidence interval (CI): -2.26, -0.75, I2=90.8%, P=0.000]. Based on these results, lowsHLA-G level in early pregnancy has a positive correlation with subsequent PE, and the significant role of sHLA-Gin the early stages of placentation can be proven.

Background and objectiveMultiple sclerosis (MS) is a chronic progressive autoimmune disorder of the central nervous system (CNS) that can cause inflammation, demyelination, and axon degeneration. Insulin-like growth factor-1 (IGF-1) is a single-chain polypeptide mainly synthesized in the liver and brain. IGF-1 causes neuronal and non-neuronal cell proliferation, survival, and differentiation. Therefore, it can be used in treating neuro-demyelinating diseases such as MS. The current systematic review and meta-analysis aims to compare the levels of IGF-1 in MS patients and healthy controls and also investigates IGF binding proteins (IGF-BP) and growth hormone (GH) levels between MS patients and healthy controls.MethodsIn this study, we systematically searched electronic databases of PubMed, Scopus, Web of Science (WOS), and Google Scholar, up to December 2022. Studies that measured IGF-1, GH, IGFBP-1, IGFBP-2, or IGFBP-3 in MS patients and healthy controls in either blood or cerebral spinal fluid (CSF) were identified. We calculated Standardized mean differences (SMD) to compare levels of IGF-1, GH, IGFBP-1, IGFBP-2, or IGFBP-3 in MS patients and controls.ResultsFinally, we included 11 eligible studies from 1998 to 2018. The sample size of included studies varied from 20 to 200 resulting in a total sample size of 1067 individuals, 531 MS patients, and 536 healthy controls. The mean age of the patient and control groups were 38.96 and 39.38, respectively. The average EDSS among patients was 4.56. We found that blood levels of IGF-1 (SMD = 0.20, 95% CI = -0.20 to 0.59, I2 = 82.4%, K = 8, n = 692), CSF level of IGF-1 (SMD = 0.25, 95% CI = -0.06 to 0.56, I2 = 0.0%, K = 3 n = 164) and blood levels of GH were not significantly higher in MS patients than controls (SMD = 0.08, 95% CI = -0.33 to 0.49, I2 = 77.0% K = 3, n = 421). Moreover, the blood levels of IGFBP-1 (SMD = 0.70, 95% CI = 0.01 to 1.40, I2 = 77%, K = 4, n = 255) were significantly higher in MS cases than in controls. However, the blood levels of IGFBP-2 (SMD = 0.43, 95% CI = -0.34 to 1.21, I2 = 64.2%, K = 3, n = 78) and blood levels of IGFBP-3 (SMD = 1.04, 95% CI = -0.09 to 2.17, I2 = 95.6%, K = 6, n = 443) were not significantly higher in patients than controls.ConclusionOur meta-analysis revealed no significant difference in serum levels of IGF-1, GH, IGFBP-2, and IGFBP-3 between the MS group and healthy controls, except for IGFBP1. However, our systematic review showed that the studies were controversial for IGFBP-3 serum levels. Some studies found an increase in serum level of IGFBP-3 in MS patients compared to the healthy group, while others showed a decrease.

Background & objectives: The resistance to insecticide among Anopheles stephensi population due to insecticide selection pressure has been previously reported from Iran. The current study was performed to evaluate the susceptibility of different insecticide reagents against An. stephensi by bioassay and molecular methods in Saravan County, a malaria-endemic area in southeastern Iran. Methods: An. stephensi mosquitoes were collected from different larval habitats in Saravan City, southeastern Iran in 2022. At first, the susceptibility of collected samples for DDT, permethrin, and deltamethrin were evaluated by bioassay test. The collected mosquitoes were then evaluated for the presence of different kdr mutations. Results: Insecticide susceptibility tests were conducted on the field population of An. stephensi from Saravan, revealing its potential resistance to pyrethroids and DDT. Of the 150 An. stephensi samples, 4 % carried the kdr L1014F mutation as heterozygous and the rest of them were homozygous L1014 wild type. Interpretation & conclusion: The current study revealed the presence of L1014F mutation for the first time in Iran. So, further monitoring of kdr mutations in the VGSC gene and resistance phenotypes should be performed.

Background and aims: Social capital, by encouraging people to collaborate and engage in social interactions, has been considered as an effective factor for development of mental disorders. In the preset study, we aimed to investigate the relationship between different aspects of social capital and psychiatric disorders in children and adolescents. Methods: This study was conducted between 2016 and 2017 in Kohgiloyeh and Boyer-Ahmad province, Iran. A total of 1001 children and adolescents aged 6-18 years and their parents were randomly selected using multistage cluster sampling to participate in the study. The data in the present study were compiled using a Persian translated version of the Kiddie-SADS-Present and Lifetime Version (K-SADS-PL) semi-structured questionnaire as well as the Social Capital Questionnaire of Nahapiet and Ghoshal. The raw data were analyzed statistically using Fisher and chi-square tests. The statistical analysis was performed using SPSS 16.0 version. Results: Our results show that better relationship, cooperation, mutual understanding, and commitment are significantly and inversely correlated to psychiatric disorders among children and adolescents. In this regard we found that the mutual understanding (P=0.008) and relationships (P=0.001) are strongly related to social capital, while other components may have more or less effects. Conclusion: Our findings show that various aspects of social capital are associated with development of psychiatric disorders in children and adolescents. Some of the social capital components including better relationship, cooperation, mutual understanding, and obligation have significant effects; however, others including networks, values and trust could not exert significant effects on mental health.

The gut microbiota undergoes significant alterations in response to viral infections, particularly the novel SARS-CoV-2. As impaired gut microbiota can trigger numerous neurological disorders, we suggest that the long-term neurological symptoms of COVID-19 may be related to intestinal microbiota disorders in these patients. Thus, we have gathered available information on how the virus can affect the microbiota of gastrointestinal systems, both in the acute and the recovery phase of the disease, and described several mechanisms through which this gut dysbiosis can lead to long-term neurological disorders, such as Guillain-Barre syndrome, chronic fatigue, psychiatric disorders such as depression and anxiety, and even neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease. These mechanisms may be mediated by inflammatory cytokines, as well as certain chemicals such as gastrointestinal hormones (e.g., CCK), neurotransmitters (e.g., 5-HT), etc. (e.g., short-chain fatty acids), and the autonomic nervous system. In addition to the direct influences of the virus, repurposed medications used for COVID-19 patients can also play a role in gut dysbiosis. In conclusion, although there are many dark spots in our current knowledge of the mechanism of COVID-19-related gut-brain axis disturbance, based on available evidence, we can hypothesize that these two phenomena are more than just a coincidence and highly recommend large-scale epidemiologic studies in the future.

BackgroundTryptophan (TRP) is an essential amino acid that must be provided in the diet. The kynurenine pathway (KP) is the main route of TRP catabolism into nicotinamide adenosine dinucleotide (NAD+), and metabolites of this pathway may have protective or degenerative effects on the nervous system. Thus, the KP may be involved in neurodegenerative diseases.ObjectivesThe purpose of this systematic review and meta-analysis is to assess the changes in KP metabolites such as TRP, kynurenine (KYN), kynurenic acid (KYNA), Anthranilic acid (AA), 3-hydroxykynurenine (3-HK), 5-Hydroxyindoleacetic acid (5-HIAA), and 3-Hydroxyanthranilic acid (3-HANA) in Alzheimer’s disease (AD), Parkinson’s disease (PD), and Huntington’s disease (HD) patients compared to the control group.MethodsWe conducted a literature search using PubMed/Medline, Scopus, Google Scholar, Web of Science, and EMBASE electronic databases to find articles published up to 2022. Studies measuring TRP, KYN, KYNA, AA, 3-HK, 5-HIAA, 3-HANA in AD, PD, or HD patients and controls were identified. Standardized mean differences (SMDs) were used to determine the differences in the levels of the KP metabolites between the two groups.ResultsA total of 30 studies compromising 689 patients and 774 controls were included in our meta-analysis. Our results showed that the blood levels of TRP was significantly lower in the AD (SMD=-0.68, 95% CI=-0.97 to -0.40, p=0.000, I2 = 41.8%, k=8, n=382), PD (SMD=-0.77, 95% CI=-1.24 to -0.30, p=0.001, I2 = 74.9%, k=4, n=352), and HD (SMD=-0.90, 95% CI=-1.71 to -0.10, p=0.028, I2 = 91.0%, k=5, n=369) patients compared to the controls. Moreover, the CSF levels of 3-HK in AD patients (p=0.020) and the blood levels of KYN in HD patients (p=0.020) were lower compared with controls.ConclusionOverall, the findings of this meta-analysis support the hypothesis that the alterations in the KP may be involved in the pathogenesis of AD, PD, and HD. However, additional research is needed to show whether other KP metabolites also vary in AD, PD, and HD patients. So, the metabolites of KP can be used for better diagnosing these diseases.

Parkinson's disease (PD), the second most common neurodegenerative disorder, is characterized by neuroinflammation, formation of Lewy bodies, and progressive loss of dopaminergic neurons in the substantia nigra of the brain. In this review, we summarize evidence obtained by animal studies demonstrating neuroinflammation as one of the central pathogenetic mechanisms of PD. We also focus on the protein factors that initiate the development of PD and other neurodegenerative diseases. Our targeted literature search identified 40 pre-clinical in vivo and in vitro studies written in English. Nuclear factor kappa B (NF-kB) pathway is demonstrated as a common mechanism engaged by neurotoxins such as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 6-hydroxydopamine (6-OHDA), as well as the bacterial lipopolysaccharide (LPS). The α-synuclein protein, which plays a prominent role in PD neuropathology, may also contribute to neuroinflammation by activating mast cells. Meanwhile, 6-OHDA models of PD identify microsomal prostaglandin E synthase-1 (mPGES-1) as one of the contributors to neuroinflammatory processes in this model. Immune responses are used by the central nervous system to fight and remove pathogens; however, hyperactivated and prolonged immune responses can lead to a harmful neuroinflammatory state, which is one of the key mechanisms in the pathogenesis of PD.

Background Approximately 20% of all transient ischaemic attacks (TIAs) and ischaemic strokes occur within the posterior circulation, with vertebrobasilar stenosis identified as the cause in roughly 25% of the cases. Studies have shown that about a quarter of these patients have atherosclerotic stenosis of at least 50% of the vertebrobasilar artery. Stenosis has been shown to be associated with an increased risk of 90-day recurrent vertebrobasilar stroke, particularly in the first few weeks, which is significantly higher when compared with patients with stenosis of the anterior circulation. Therefore, aggressive treatment is important for the patient’s prognosis. Stenting is emerging as a promising therapeutic strategy for persistent ischaemia events that do not respond to the best medical treatment, but it is not without complications. We systematically reviewed the literature on percutaneous transluminal angioplasty and stenting (PTAS) for intracranial vertebrobasilar artery stenosis (IVBS).Methods PubMed, Web-of-Science and Scopus were searched upon the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to include prospective/retrospective cohort, randomised/non-randomised clinical trials and case series studies describing PTAS for IVBS. Pooled rates of intervention-related complications and outcomes were analysed with random-effect model meta-analysis using StataMP V.18.0 software.Results 31 studies were found eligible which included 1928 cases. 1103 basilar artery stenosis cases were reported in 27 studies 0.65 (95% CI 0.53, 0.76), I2: 99.72%. 648 vertebral cases were reported in 18 studies 0.60 (95% CI 0.49, 0.70), I2: 97.49%. In four studies, the rate of vertebrobasilar stenosis cases calculated as a proportion of the total sample size was 0.10 (95% CI 0.05, 0. 15). Mean stenosis in 21 included studies was found to be 0.83 (95% CI 0.79, 0.88), I2: 0.00%, which shows variation of baseline stenosis between studies was minimal. 51 deaths were recorded in 24 studies. Meta-analysis of mortality showed the overall rate of mortality was 0.03 (95% CI 0.02, 0.05), I2: 44.90%. In 14 studies, symptomatic intracranial haemorrhage events were recorded at an overall rate of 0.01 (95% CI 0.00, 0.02), I2: 0.00%. Generally, a follow-up period of at least 3 months was reported in the included studies. Furthermore, procedural stroke/TIA was evaluated in seven studies, four of which reported no events (0.03 (95% CI 0.00, 0.08), I2: 20.38%). Mean time from initial symptoms to recanalisation was 23.98 (95% CI 18.56, 29.40), I2=98.8%, p=0.00 days.Conclusion In certain individuals with medically unresolved, severe, symptomatic and non-acute IVBS, elective vertebrobasilar PTAS appears to be both safe and effective. Various stent designs and angioplasty-assisted techniques should be taken into consideration based on the specific clinical and radiological traits of the lesions. Future randomised controlled trials are required to verify these results.