The Schiff base hydrazine copper(II) complexes induce apoptosis by P53 overexpression and prevent cell migration through protease-independent pathways.

Although chemotherapy has increased the life expectancy of cancer patients, its toxic side effects remain a major challenge. Recently, organometallic compounds, such as Schiff base copper complexes, have become promising candidates for next-generation anticancer drugs owing to their unique anticancer activities. In this study, binuclear copper(II) complex-1 and mononuclear copper(II) complex-2 were examined to analyze their anticancer mechanisms further. For this purpose, a viability test, flow cytometry analysis of apoptosis and the cell cycle, migration assay, and gene expression analysis were performed. According to our results, complex-1 was more cytotoxic than complex-2 at 24/48-h intervals. Our findings also demonstrated that both complexes induced apoptosis at IC50 concentrations and arrested the cell cycle at the G1-S checkpoint. However, complex-1 accelerates cell cycle arrest at the sub-G0/G1 phase more than complex-2 does. Furthermore, gene expression analysis showed that only complex-1 induces the expression of p53. Interestingly, both complexes induced Bcl-2 overexpression. However, they did not affect MMP-13 expression. More interestingly, both complexes inhibited cell migration in different ways, including amoeboid and collective, by recruiting protease-independent pathways. This study confirmed that adding several metal cores and co-ligands increased the activity of the complex. It also appeared that Cu-containing complexes could prevent the migration of cancer cells through protease-independent pathways, which can be used for novel therapeutic purposes.

Association Study between DUF1220 Copy Number and Severity of Social Impairment in Sex-balanced Simplex Cases of Autism.

Introduction: Copy number variations (CNVs), which are genetic factors responsible for human evolution, have emerged as underlying pathogenic factors for a number of diseases such as autism spectrum disorders (ASD). DUF1220 coding sequences have been shown to be positively associated with the severity of symptoms in familial/multiplex cases of autism. However, this association has not been confirmed in simplex autism, and the potential impact of gender/sex has not been studied. Methods: Using saliva samples taken from Iranian children with non-syndromic simplex autism, different ethnicity/race and genetic backgrounds from previous studies, we assessed the association between DUF1220 CNVs and Autism Diagnostic Interview-Revised (ADI-R) domain scores in both males and females. Results: In the male and female combined group with autism, in line with previous reports, our findings showed that there were no significant associations between DUF1220 CNVs with either total ADI-R score, social, communication, or repetitive diagnostic scores in simplex autism cases. Interestingly, however, in sex classified groups, despite the insignificant results, our findings in girls with autism showed a negative trend between DUF1220 CNVs and severity of symptoms for the social interaction and communication domains. By contrast, in male children with autism, the results showed a positive trend. Conclusion: It seems that association of DUF1220 CNV with the severity of symptoms in simplex children with autism may follow a sexually dimorphic pattern that needs to be re-examined in prospective studies.

Sexual Dimorphism in Telomere Length in Childhood Autism.

Autism spectrum disorders (ASD) are strikingly more prevalent in males, but the molecular mechanisms responsible for ASD sex-differential risk are poorly understood. Abnormally shorter telomeres have been associated with autism. Examination of relative telomere lengths (RTL) among non-syndromic male (N = 14) and female (N = 10) children with autism revealed that only autistic male children had significantly shorter RTL than typically-developing controls (N = 24) and paired siblings (N = 10). While average RTL of autistic girls did not differ significantly from controls, it was substantially longer than autistic boys. Our findings indicate a sexually-dimorphic pattern of RTL in childhood autism and could have important implications for RTL as a potential biomarker and the role/s of telomeres in the molecular mechanisms responsible for ASD sex-biased prevalence and etiology.

Enhancement of nerve regeneration with nimodipine treatment after sciatic nerve injury.

Peripheral nerve injuries (PNI/s) are common orthopedic conditions, characterized by motor and sensory deficits in the damaged region. There is growing evidence that the L-type calcium channel antagonist nimodipine has neuroprotective and neuroregenerative effects in animal models of neurological disorders. The efficacy of nimodipine on improving motor function and sensation following a sciatic nerve crush model was investigated in male Wistar rats as a model of PNI. At different time periods following damage, we evaluated motor function, sensory recovery, electrophysiology, histomorphometry, and gene expression. Moreover, we used histological and mass ratio analysis of the gastrocnemius muscle to assess atrophy. Our findings suggest that the nimodipine improves motor and sensory function more quickly in the damaged region 2, 4, and 6 weeks after 1 week of treatment. Nimodipine treatment also increased the number of myelinated fibers while decreasing their thickness, as shown by histomorphometry. Additionally, nimodipine treatment increases the mRNA levels of neurotrophic factors (BDNF and NGF), which are known to contribute to the regeneration of injured neurons. The impact of nimodipine in PNI recovery may be due to its stimulation of the CREB signaling pathway and suppression of pro-inflammatory factor production.

Can anti-parasitic drugs help control COVID-19?

Novel COVID-19 is a public health emergency that poses a serious threat to people worldwide. Given the virus spreading so quickly, novel antiviral medications are desperately needed. Repurposing existing drugs is the first strategy. Anti-parasitic drugs were among the first to be considered as a potential treatment option for this disease. Even though many papers have discussed the efficacy of various anti-parasitic drugs in treating COVID-19 separately, so far, no single study comprehensively discussed these drugs. This study reviews some anti-parasitic recommended drugs to treat COVID-19, in terms of function and in vitro as well as clinical results. Finally, we briefly review the advanced techniques, such as artificial intelligence, that have been used to find effective drugs for the treatment of COVID-19.

Selection of Suitable Reference Genes for Analysis of Salivary Transcriptome in Non-Syndromic Autistic Male Children.

Childhood autism is a severe form of complex genetically heterogeneous and behaviorally defined set of neurodevelopmental diseases, collectively termed as autism spectrum disorders (ASD). Reverse transcriptase quantitative real-time PCR (RT-qPCR) is a highly sensitive technique for transcriptome analysis, and it has been frequently used in ASD gene expression studies. However, normalization to stably expressed reference gene(s) is necessary to validate any alteration reported at the mRNA level for target genes. The main goal of the present study was to find the most stable reference genes in the salivary transcriptome for RT-qPCR analysis in non-syndromic male childhood autism. Saliva samples were obtained from nine drug naïve non-syndromic male children with autism and also sex-, age-, and location-matched healthy controls using the RNA-stabilizer kit from DNA Genotek. A systematic two-phased measurement of whole saliva mRNA levels for eight common housekeeping genes (HKGs) was carried out by RT-qPCR, and the stability of expression for each candidate gene was analyzed using two specialized algorithms, geNorm and NormFinder, in parallel. Our analysis shows that while the frequently used HKG ACTB is not a suitable reference gene, the combination of GAPDH and YWHAZ could be recommended for normalization of RT-qPCR analysis of salivary transcriptome in non-syndromic autistic male children.

Optimized quantities of GDNF overexpressed by engineered astrocytes are critical for protection of neuroblastoma cells against 6-OHDA toxicity.

Optimized levels of glial cell line-derived neurotrophic factor (GDNF) are critical for protection of dopaminergic neurons against parkinsonian cell death. Recombinant lentiviruses harboring GDNF coding sequence were constructed and used to infect astrocytoma cell line 1321N1. The infected astrocytes overexpressed GDNF mRNA and secreted an average of 2.2 ng/mL recombinant protein as tested in both 2 and 16 weeks post-infection. Serial dilutions of GDNF-enriched conditioned medium from infected astrocytes added to growing neuroblastoma cell line SK-N-MC resulted in commensurate resistance against 6-OHDA toxicity. SK-N-MC cell survival rate rose from 51% in control group to 84% in the cells grown with astro-CM containing 453 pg secreted GDNF, an increase that was highly significant (P < 0.0001). However, larger volumes of the GDNF-enriched conditioned medium failed to improve cell survival and addition of volumes that contained 1,600 pg or more GDNF further reduced survival rate to below 70%. Changes in cell survival paralleled to changes in the percent of apoptotic cell morphologies. These data demonstrate the feasibility of using astrocytes as minipumps to stably oversecrete neurotrophic factors and further indicate that GDNF can be applied to neuroprotection studies in PD pending the optimization of its concentrations.