MicroRNA-124 Overexpression in Associated with Lymph Node Metastasis in Breast Cancer

Breast cancer as a heterogeneous sophisticated disease includes several group with discrete clinical consequences. The disease is the most prevalent malignancy after non-melanoma skin cancers and it is also considered as the second leading cause of death after lung cancer. In fact, breast cancer is account for 23% of all cancer cases and 14% of deaths from cancer. The major cause of breast cancer deaths is actually metastasis of the tumor. As a result, it is prominent to identify the disease mechanism and diagnose molecular tools in order to predict metastasis. The specimens were collected from 30 metastatic and 30 primary tumor tissues of breast cancer patients. After that, RNA extraction was accomplished by means of GeneAll kit and then was stored in -80 degrees. Then, cDNA synthesis was carried out by miscript II RT kit from Qiagenecompany. Finally, sybergreen Real Time PCR of all samples was done for miRNA124, miRNA130a and miRNA 16 as a reference by means of Pre-designed primers of Qiagene Company. The results of molecular expression study showed that the amount of miRNA 124 in metastatic tissues has approximately increased double of primary tumor tissues. It is also revealed that the amount of miRNA has similarly increased by about 1.7 times. According to recent results, it can be possible to regard molecule as a major cause of metastasis process in breast cancer.

In Vitro Cytotoxicity Of Folate-Silica-Gold Nanorods On Mouse Acute Lymphoblastic Leukemia And Spermatogonial Cells

Objective The purpose of this study was to evaluate in vitro cytotoxicity of gold nanorods (GNRs) on the viability of spermatogonial cells (SSCs) and mouse acute lymphoblastic leukemia cells (EL4s). Materials And Methods In this experimental study, SSCs were isolated from the neonate mice, following enzymatic digestion and differential plating. GNRs were synthesized, then modified by silica and finally conjugated with folic acid to form F-Si-GNRs. Different doses of F-Si-GNRs (25, 50, 75, 100, 125 and 140 µM) were used on SSCs and EL4s. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) proliferation assay was performed to examine the GNRs toxicity. Flow cytometry was used to confirm the identity of the EL4s and SSCs. Also, the identity and functionality of SSCs were determined by the expression of specific spermatogonial genes and transplantation into recipient testes. Apoptosis was determined by flow cytometry using an annexin V/propidium iodide (PI) kit. Results Flow cytometry showed that SSCs and EL4s were positive for Plzf and H-2kb, respectively. The viability percentage of SSCs and EL4s that were treated with 25, 50, 75, 100, 125 and 140 µM of F-Si-GNRs was 65.33 ± 3.51%, 60 ± 3.6%, 51.33 ± 3.51%, 49 ± 3%, 30.66 ± 2.08% and 16.33 ± 2.51% for SSCs and 57.66 ± 0.57%, 54.66 ± 1.5%, 39.66 ± 1.52%, 12.33 ± 2.51%, 10 ± 1% and 5.66 ± 1.15% for EL4s respectively. The results of the MTT assay indicated that 100 µM is the optimal dose to reach the highest and lowest level of cell death in EL4s and in SSCs, respectively. Conclusion Cell death increased with increasing concentrations of F-Si-GNRs. Following utilization of F-Si-GNRs, there was a significant difference in the extent of apoptosis between cancer cells and SSCs

sj-docx-1-pev-10.1177_22840265241240212 – Supplemental material for Shared biological features between ovarian cancer and endometriosis based on co-expression networks analysis

Supplemental material, sj-docx-1-pev-10.1177_22840265241240212 for Shared biological features between ovarian cancer and endometriosis based on co-expression networks analysis by Abolfazl Mehdizadeh Kashi, Samaneh Rokhgireh, Shahla Chaichian, Nadia Barjaste, Neda Eslahi, Marziyeh Ajdary, Kobra Tahermanesh and Sara Minaeian in Journal of Endometriosis and Pelvic Pain Disorders</p

In vitro development of embryos from experimentally Kerack-addicted Mice

Background: Prenatal drug exposure, as a common public health concern, is associated with an increased risk of adverse effects on early embryo development. Objective: To investigate the in vitro development of - embryo from experimentally Kerack-addicted mice. Materials and Methods: Twenty-five female mice were studied in five groups: control, vehicle, and three experimental groups of Kerack-dependent mice (I, II, and III) which received different doses of Kerack for 14 days. After the establishment of addiction model (7 days), experimental groups I, II, and III were given Kerack intraperitoneally at the doses of 5, 35, and 70 mg/kg, twice a day for a period of 7 days, respectively. The vehicle group received normal saline and lemon juice whilst the control group just received water and food. Morulae were obtained through oviduct flashing. The survived embryos were cultured in T6+ 5mg/ml bovine serum albumin. The developmental rates up to hatched stage daily and embryo quality (differential staining and Tunnel staining) were also assessed Results: The developmental potential of embryos obtained from the addicted mother was significantly decreased in comparison with control group. There was a significant reduction in the rate of blastocyst formation in the high dose Kerack dependent group. However, in addicted mice there was reduction in the total cell number (40.92% vs. 65.08% in control) and, inner cell mass percentage (17.17% vs. 26.15% in control) while apoptotic cells numbers were increased (7.17 vs. 1.46 in control) (p<0.05). Conclusion: The Kerack addiction during pregnancy retards preimplantation development and induces apoptosis

Triple combination of heat, drug and radiation using alginate hydrogel co-loaded with gold nanoparticles and cisplatin for locally synergistic cancer therapy

Although multimodal cancer therapy has shown superior antitumor efficacy in comparison to individual therapy due to the potential generation of synergistic interactions among the treatments, its clinical usage is highly hampered by systemic dose-limiting toxicities. Herein, we developed a multi-responsive nanocomplex constructed from alginate hydrogel co-loaded with cisplatin and gold nanoparticles (AuNPs) (abbreviated as ACA) to combine chemotherapy, radiotherapy (RT) and photothermal therapy. The nanocomplex markedly improved the efficiency of drug delivery where ACA resulted in noticeably higher tumor growth inhibition than free cisplatin. The tumor treated with ACA showed an increased heating rate upon 532 nm laser irradiation, indicating the photothermal conversion ability of the nanocomplex. While RT alone resulted in slight tumor growth inhibition, thermo-chemo therapy, chemoradiation therapy and thermo-radio therapy using ACA dramatically slowed down the rate of tumor growth. Upon 532 nm laser and 6 MV X-ray, the nanocomplex could enable a trimodal thermo-chemo-radio therapy that yielded complete tumor regression with no evidence of relapse during the 90-days follow up period. The results of this study demonstrated that the incorporation of AuNPs and cisplatin into alginate hydrogel network can effectively combine chemotherapy, RT and photothermal therapy to achieve a locally synergistic cancer therapy. (C) 2020 Elsevier B.V. All rights reserved

The conserved p.Arg108 residue in S1PR2 (DFNB68) is fundamental for proper hearing: evidence from a consanguineous Iranian family

Background: Genetic heterogeneity and consanguineous marriages make recessive inherited hearing loss in Iran the second most common genetic disorder. Only two reported pathogenic variants (c.323G>C, p.Arg108Pro and c.419A>G, p.Tyr140Cys) in the S1PR2 gene have previously been linked to autosomal recessive hearing loss (DFNB68) in two Pakistani families. We describe a segregating novel homozygous c.323G>A, p.Arg108Gln pathogenic variant in S1PR2 that was identified in four affected individuals from a consanguineous five generation Iranian family. Methods: Whole exome sequencing and bioinformatics analysis of 116 hearing loss-associated genes was performed in an affected individual from a five generation Iranian family. Segregation analysis and 3D protein modeling of the p.Arg108 exchange was performed. Results: The two Pakistani families previously identified with S1PR2 pathogenic variants presented profound hearing loss that is also observed in the affected Iranian individuals described in the current study. Interestingly, we confirmed mixed hearing loss in one affected individual. 3D protein modeling suggests that the p.Arg108 position plays a key role in ligand receptor interaction, which is disturbed by the p.Arg108Gln change. Conclusion: In summary, we report the third overall mutation in S1PR2 and the first report outside the Pakistani population. Furthermore, we describe a novel variant that causes an amino acid exchange (p.Arg108Gln) in the same amino acid residue as one of the previously reported Pakistani families (p.Arg108Pro). This finding emphasizes the importance of the p.Arg108 amino acid in normal hearing and confirms and consolidates the role of S1PR2 in autosomal recessive hearing loss

Additional file 1: of The conserved p.Arg108 residue in S1PR2 (DFNB68) is fundamental for proper hearing: evidence from a consanguineous Iranian family

List of exome panel evaluated genes with OMIM number. (DOCX 21 kb

A relatively common homozygous TRAPPC4 splicing variant is associated with an early-infantile neurodegenerative syndrome

Trafficking protein particle (TRAPP) complexes, which include the TRAPPC4 protein, regulate membrane trafficking between lipid organelles in a process termed vesicular tethering. TRAPPC4 was recently implicated in a recessive neurodevelopmental condition in four unrelated families due to a shared c.454+3A&gt;G splice variant. Here, we report 23 patients from 17 independent families with an early-infantile-onset neurodegenerative presentation, where we also identified the homozygous variant hg38:11:119020256 A&gt;G (NM_016146.5:c.454+3A&gt;G) in TRAPPC4 through exome or genome sequencing. No other clinically relevant TRAPPC4 variants were identified among any of over 10,000 patients with neurodevelopmental conditions. We found the carrier frequency of TRAPPC4 c.454+3A&gt;G was 2.4-5.4 per 10,000 healthy individuals. Affected individuals with the homozygous TRAPPC4 c.454+3A&gt;G variant showed profound psychomotor delay, developmental regression, early-onset epilepsy, microcephaly and progressive spastic tetraplegia. Based upon RNA sequencing, the variant resulted in partial exon 3 skipping and generation of an aberrant transcript owing to use of a downstream cryptic splice donor site, predicting a premature stop codon and nonsense mediated decay. These data confirm the pathogenicity of the TRAPPC4 c.454+3A&gt;G variant, and refine the clinical presentation of TRAPPC4-related encephalopathy