A systematic review of novel cannabinoids and their targets: Insights into the significance of structure in activity.

To provide a comprehensive framework of the current information on the potency and efficacy of interaction between phyto- and synthetic cannabinoids and their respective receptors, an electronic search of the PubMed, Scopus, and EMBASE literature was performed. Experimental studies included reports of mechanistic data providing affinity, efficacy, and half-maximal effective concentration (EC50). Among the 108 included studies, 174 structures, and 16 targets were extracted. The most frequent ligands belonged to the miscellaneous category with 40.2% followed by phytocannabinoid-similar, indole-similar, and pyrrole-similar structures with an abundance of 17.8%, 16.6%, and 12% respectively. 64.8% of structures acted as agonists, 17.1 % appeared as inverse agonists, 10.8% as antagonists, and 7.2% of structures were reported with antagonist/inverse agonist properties. Our outcomes identify the affinity, EC50, and efficacy of the interactions between cannabinoids and their corresponding receptors and the subsequent response, evaluated in the available evidence. Considering structures' significance and very important effects of on the activities, the obtained results also provide clues to drug repurposing.

The novel anti-fibrillary effects of volatile compounds α-asarone and ß-caryophyllene on tau protein: Towards promising therapeutic agents for Alzheimer's disease.

The abnormal deposition of tau protein is one of the critical causes of tauopathies including Alzheimer's disease (AD). In recent years, there has been great interest in the use of essential oils and volatile compounds in aromatherapy for treating AD, since volatile compounds can directly reach the brain through intranasal administration. The volatile compounds α-asarone (ASA) and ß-caryophyllene (BCP) have revealed various important neuroprotective properties, useful in treating AD. In this study, the volatile compounds ASA and BCP were assessed for their effectiveness in preventing tau fibrillation, disassembly of pre-formed tau fibrils, and disaggregation of tau aggregates. SDS-PAGE and AFM analyses revealed that ASA and BCP inhibited tau fibrillation/aggregation and decreased the mean size of tau oligomers. Tau samples treated with ASA and BCP, showed a reduction in ThT and ANS fluorescence intensities, and a decrease in the ß-sheet content. Additionally, ASA and BCP disassembled the pre-formed tau fibrils to the granular and linear oligomeric intermediates. Treatment of neuroblastoma SH-SY5Y cells with tau samples treated with ASA and BCP, revealed protective effects as shown by reduced toxicity of the cells, due to the inhibition of tau fibrillation/aggregation. Overall, ASA and BCP appeared to be promising therapeutic candidates for AD.

Unravelling the Novel Effects of Three Volatile Compounds in Preventing Fibril Formation of Disease Related Tau and α-Synuclein Proteins- Towards Identifying Candidate Aromatic Substances for Treating Neurodegenerative Diseases.

Background: The aggregation of tau and α-synuclein into fibrillary assemblies in nerve cells is the molecular hallmark of Alzheimer's and Parkinson's diseases, respectively. In our previous studies, we investigated the anti-amyloidogenic effects of three different aroma-producing (volatile) compounds including cinnamaldehyde, phenyl ethyl alcohol, and TEMED on the fibrillation process of HEWL, as a model protein. Our previous results showed that while TEMED was able to completely stop the process of fibril formation, cinnamaldehyde and phenyl ethyl alcohol gave rise to oligomeric/protofibrillar forms and were involved in the entrapment of intermediate species of HEWL. In this study, we investigated the anti-amyloidogenic effect of the same three volatile compounds on recombinantly produced tau and α-synuclein proteins. Methods: The thioflavin T fluorescence assay, circular dichroism, SDS-PAGE/native-PAGE, dynamic light scattering, and atomic force microscopy were used, where necessary, to further our understanding of the inhibitory effects of the three volatile compounds on the fibril formation of tau and α-synuclein proteins and allow for a comparison with previous data obtained for HEWL. Results: Our results revealed that contrary to the results obtained for HEWL (a globular protein), the volatile compound TEMED was no longer able to prevent fibril formation in either of the natively unstructured tau or α-synuclein proteins, and instead, cinnamaldehye and phenyl ethyl alcohol, in particular, had the role of preventing fibril formation of tau or α-synuclein. Conclusion: The results of this study further emphasized the exclusion of HEWL as a model protein for fibrillation studies and highlighted the importance of studying brain-related proteins such as tau or α-synuclein and the need to assess the effects of volatile compounds such as cinnamaldehye and phenyl ethyl alcohol as potential substances in the treatment of neurodegenerative diseases.

An Infertile Azoospermic Male With 45, X T(Yp;15) Karyotype.

Objective: 45, X is a very rare condition that usually results from Y/autosomal translocations or insertions. Here we present an infertile azoospermic man who had 45, X t(Yp;15) karyotype and deletion of AZF (azoospermia factor) gene region. Case report : A 35-year-old infertile azoospermic man with a typical male appearance came for infertility genetic counseling. He was infertile for more than ten years and had short height. High-resolution of metaphase chromosomes of 50 peripheral white blood cells were analyzed for karyotyping. Fluorescence in situ hybridization (FISH) analysis and Polymerase chain reaction (PCR) were done for SRY and AZF gene localization. Karyotyping and FISH analysis revealed 45, X t(Yp;15) karyotype and no mosaicism. More investigation on the Y chromosome revealed no deletion in the SRY region, but AZF a/b/c were deleted. It was revealed that Yp's subtelomeric region but not Yq was translocated to chromosome 15. Conclusion: This study shows that despite the lack of a complete Y chromosome in this person, the occurrence of secondary male traits is a result of the short arm translocation of the Y chromosome, which contains the (ex-determining region Y) SRY gene. Infertility is also due to the Y chromosomes long arm's deletion containing the AZF gene region.

Prenatal Diagnosis of Mosaic Tetrasomy 18p in a Case without Sonographic Abnormalities.

Small supernumerary marker chromosomes (sSMC) are still a major problem in clinical cytogenetics as they cannot be identified or characterized unambiguously by conventional cytogenetics alone. On the other hand, and perhaps more importantly in prenatal settings, there is a challenging situation for counseling how to predict the risk for an abnormal phenotype, especially in cases with a de novo sSMC. Here we report on the prenatal diagnosis of a mosaic tetrasomy 18p due to presence of an sSMC in a fetus without abnormal sonographic signs. For a 26-year-old, gravida 2 (para 1) amniocentesis was done due to consanguineous marriage and concern for Down syndrome, based on borderline risk assessment. Parental karyotypes were normal, indicating a de novo chromosome aberration of the fetus. FISH analysis as well as molecular karyotyping identified the sSMC as an i(18)(pter->q10:q10->pter), compatible with tetrasomy for the mentioned region. Cordocentesis was done due to normal sonography and the results from amniocentesis were confirmed. The parents opted for pregnancy termination and post mortem examination now noted, low anterior hairline, large philtrum, low-set posteriorly rotated malformed ears with prominent antihelix, lower limbs joint contracture and digital anomalies, including long and narrow toes with clinodactyly of the 1st and 5th toes and postaxial polydactyly of one hand. De novo i(18p) can be considered as a special case in the sense that the major relevant phenotypes mentioned for it, i.e. feeding difficulties, abnormalities in muscle tone and developmental/mental retardation, cognitive and behavioral characteristics, recurrent otitis media and seizures, are mostly postnatal. This emphasizes the necessity to determine the nature of a de novo euchromatic marker chromosome, especially in cases with normal ultrasound result and the suitability of a cordocentesis in order to better predicting the pregnancy outcome and parental counseling.

Relative frequency of human papillomavirus genotypes and related sociodemographic characteristics in women referred to a general hospital in Tehran, 2014-2015: A cross-sectional study.

BACKGROUND: Human papilloma virus (HPV) is one of the major public health problems and the main causes of cervical cancer. The prevalence HPV infection in developing countries with low financial resources is high. OBJECTIVE: This study aimed to determine the relative frequency of HPV genotypes and its sociodemographic characteristics in women referred to a general hospital in Tehran, Iran from 2014-2015. MATERIALS AND METHODS: This cross-sectional study was performed in 400 women with Pap smear samples, referring to to a general hospital in Tehran, Iran from 2014-2015. The detection of 28 HPV genotypes was performed by using the Multiplex PCR technique. The sociodemographic survey was conducted for each HPV positive woman. RESULTS: HPV-positive infection was detected in 155 (38.75%) women aged 17-85 years. HPV 16 (19.1%) was the most prevalent type, followed by HPV 39 (12.5%) and HPV 18 (8.9%). The highest rate of HPV infection was observed at the age of 36 years (7.7%). The level of education and economic situation of each woman were showed most of HPV-positive women had a high school diploma (34.6%) and average economic situation (67,9%). 60.9% of these women were a housewife, and 67.3% lived in the capital . CONCLUSION: Determination of HPV genotype and risk factor related to HPV infection in each geographical region can lead to the production of effective vaccines against the HPV virus. It can also be useful for disease management and high sensitivity diagnosis of cervical intraepithelial neoplasia.