Molecular Biology Research Communications最新文献

Scorpion venom contains various toxin peptides with pharmacological and biological properties. Scorpion toxins specifically interact with membrane ion channels which play key roles in progression of cancer. Therefore, scorpion toxins have received special attention for targeting cancer cells. Two new toxins MeICT and IMe-AGAP, isolated from Iranian yellow scorpion, Mesobuthus eupeus, interact specifically with chloride and sodium channels, respectively. Anti-cancer properties of MeICT and IMe-AGAP have been determined before, in addition they show 81 and 93% similarity with two well-known anti-cancer toxins, CTX and AGAP, respectively. The aim of this study was construction of a fusion peptide MeICT/IMe-AGAP to target different ion channels involved in cancer progression. Design and structure of the fusion peptide were investigated by bioinformatics studies. Two fragments encoding MeICT and IMe-AGAP were fused using overlapping primers by SOEing-PCR. MeICT/IMe-AGAP chimeric fragment was cloned into pET32Rh vector, expressed in Escherichia coli host and analyzed by SDS-PAGE. The in silico studies showed that chimeric peptide with GPSPG linker preserved the three-dimensional structure of both peptides and can be functional. Due to the high expression of chloride and sodium channels in various cancer cells, MeICT/IMe-AGAP fusion peptide can be used as an effective agent to target both channels in cancers, simultaneously.

Human leukocyte antigen-DQB1 (HLA-DQB1, OMIM: 604305) is the human major histocompatibility complex (MHC) system. HLA genes are classified into three classes (I, II, and III). The HLA-DQB1 belongs to class II, is mainly involved in the actions of the human immune system and plays a fundamental role in donor-recipient matching in transplantation and can be associated with most autoimmune diseases. In this study, the potential influence(s) of the G-71C (rs71542466) and T-80C (rs9274529) genetic polymorphisms were investigated. These polymorphisms, located in the HLA-DQB1 promoter region, have a significant frequency in the world population. The online software ALGGEN-PROMO.v8.3 was used in this work. The results indicate that the C allele at the -71 position actually creates a new potential binding site for NF1/CTF and the C allele at the -80 position changes the TFII-D binding site into a GR-alpha response element. The NF1/CTF plays the role of activator and the GR-alpha is the inhibitor; thus, according to the roles of these transcription factors, it is suggested that the above-mentioned polymorphisms alter the expression levels of HLA-DQB1. Therefore, this genetic variation is associated with autoimmune diseases; however, this cannot be generalized because this is the first report and more studies are needed in the future.

Toxicity and autophagy effects of a new complex of platinum II (CPC) were evaluated on HeLa cells cultured on a PCL/gelatin electrospinning scaffold. HeLa cells were treated with CPC on the first, third, and fifth days and the concentration of IC₅₀ was determined. The autophagic and apoptotic effects of CPC were examined by MTT assay, Acridine Orange, Giemsa, DAPI, MDC, real-time PCR, Western blot testing, and molecular docking. The cell viability was obtained on days 1, 3, and 5 as much as 50, 7.28, and 19%, respectively with a concentration of IC₅₀ (100μM) of CPC. The staining results indicated that the treatment of HeLa cells with CPC had antitumor and autophagic effects. Results of RT-PCR showed that the expression of BAX, BAD, P53, and LC3 genes was significantly increased in the sample treated with IC₅₀ concentration compared to the control sample whereas the expression of BCL2, mTOR, and ACT genes in cells was significantly decreased compared to the control group. Also, these results were confirmed by Western blotting. The data indicated the induction of apoptotic death and autophagy in the studied cells. The new compound of CPC has antitumor effects.

Canine hepatozoonosis is a tick-transmitted apicomplexan infection caused by two species of Hepatozoon, H. canis, and H. americanum. The present research aimed at detection of Hepatozoon spp. in dogs and its effects on hematological alterations. Blood samples were taken from 108 dogs to assess Hepatozoon spp. Phylogenetic analysis was performed based on the 18S rDNA marker by PCR assay and Giemsa-stained blood smear examination. Of the 108 blood samples of dogs tested in the present study, eight (7.40%, 95% CI: 3.25-14.07%) were positive by the Hepatozoon-specific PCR assay. However, in the microscopic examination, only one sample (0.93%) was positive. All of the sequenced samples were H. canis. The Hepatozoon sequences obtained from PCR amplicons in the canine-positive cases exhibited 100% similarity to each other and 98.47-100% similarity to other relevant sequences in GenBank. These findings represent the first molecular evidence of H. canis in dog populations in South Iran. Furthermore, according to the hematological analysis, significantly higher average numbers of neutrophils and lymphocytes were found in the infected group compared to the non-infected dogs. In this study, no statistically significant connection (P<0.05) was observed between H. canis infection and the examined risk factors.

Thyroid cancer is the most common malignancy of the endocrine system. LncRNAs play critical role in various cellular processes and are associated with several diseases. CCAT2 is a lncRNA molecule overexpressed in thyroid cancer. Single nucleotide polymorphisms in CCAT2 gene can cause changes in the structure and function of CCAT2 transcripts and susceptibility to several diseases. This study aimed to evaluate the association of rs6983267 in CCAT2 gene with thyroid cancer susceptibility in the Azeri population of Iran. In this "case-control" study, genomic DNA was extracted from peripheral blood of 102 individuals affected by thyroid cancer and 103 healthy individuals as controls. Genotyping was performed using TETRA-ARMS polymerase chain reaction. Statistical analysis showed no significant association between genotypes and/or alleles with the occurrence of thyroid cancer in the studied population, patients' gender, and tumor type. Nevertheless, we found that the allelic and genotypic distribution of this SNP was associated with the size of thyroid tumors in patients. It is assumed that investigating more individuals from both case and control group may further determine the genotypic and allelic frequencies of this SNP locus in Iranian-Azeri population.

Human BK polyomavirus (BKPyV) is a latent infectious agent in the genitourinary tract associated with hemorrhagic cystitis and nephropathy. This virus can be a risk factor for various human malignancies, including prostate cancer (PCa). It may contribute to prostate cancer development, as it demonstrates oncogenic properties by encoding oncoproteins. This study assessed the prevalence of this virus in benign and malignant prostate tissues. Between 2009 and 2019, 49 formalin-fixed paraffin-embedded (FFPE) PCa and 49 benign prostatic hyperplasia (BPH) samples were gathered from the pathology department of a tertiary care university hospital. They were used as cases and controls, respectively. After deparaffinization and DNA extraction, nested PCR was applied to identify the BKPyVgp5 gene (LTAg) using inner and outer primers. The nested PCR showed a 278-bp bond corresponding to the BKPyVgp5 genome (LTAg) in 53.1% (26/49) of PCa and 14.3% (7/49) of BPH (p<0.001). The presence of BKV was significantly associated with an increased risk of PCa development (OR=6.78, 95% CI=2.55-18.02, p<0.001). The BKV LTAg gene was significantly more prevalent in PCa samples than in BPH samples. These results demonstrate the presence of the virus in prostate cancer tissues.

There has been a concerning increase in the incidence of autoimmune diseases following SARS-CoV-2 infection, with molecular mimicry proposed as a potential mechanism. Our study identified nine fertility-associated proteins (AMH, BMP2, CUBN, DNER, ERCC1, KASH5, MSLN, TPO, and ZP3) that exhibit potential molecular mimicry with MHC-II epitopes of SARS-CoV-2 proteins (N, ORF1A, ORF1AB, and S). We screened for epitopes based on in silico binding using DR-, DQ-, and DP-haplotypes that predispose susceptible individuals to autoimmune diseases. Our systematic analysis revealed that 41 countries with population coverage of over 50% had a pre-COVID pandemic total fertility rate of less than 2.1 births per woman. With over 761 million people from 229 countries and territories infected since December 2019, there may be a potential for a foreseeable negative effect on fertility in specific countries, particularly in high-income economies experiencing rapid demographic changes.

Despite various treatment options available for colorectal cancer, the survival rates for patients remain low. This study investigated the effects of hyperthermia and Ibuprofen on human colorectal adenocarcinoma cells (HT-29) viability, proliferation, and gene expression related to tumor suppression, Wnt signaling pathways, proliferation, and apoptosis The cells were exposed to hyperthermia at 42 or 43°C for 3 hours or Ibuprofen at different concentrations (700-1500 μM), and the effects were analyzed through MTT assay, trypan blue staining, and quantitative Real-time PCR. The study used quantitative Real-time PCR (qRT-PCR) to evaluate the effect of hyperthermia and Ibuprofen on the expression of various genes associated with tumor suppression, proliferation, Wnt signaling pathway, and apoptosis. The results revealed that hyperthermia caused a minor reduction in the viability and proliferation of HT-29 cells, but the decrease was not statistically significant (P<0.05). On the other hand, Ibuprofen caused a concentration-dependent decrease in the viability and proliferation of HT-29 cells. Both hyperthermia and Ibuprofen reduced the expression of WNT1, CTNNB1, BCL2, and PCNA genes, and increased the expression of KLF4, P53, and BAX genes. However, the changes in gene expression were not statistically significant in cells treated with hyperthermia. The findings suggest that Ibuprofen is more effective in reducing cancer cell proliferation by promoting apoptosis and inhibiting the Wnt signaling pathway than hyperthermia, which had some impact but was not statistically significant. The study highlights the potential of Ibuprofen as a targeted therapy for colorectal cancer.

The human epidermal growth factor receptor (EGFR/ErbB) family consists of four members (ErbB1-4) and belongs to the superfamily of receptor tyrosine kinases (RTKs). The ErbB family members participate in multiple cellular pathways and are the key players in several cancers (brain, breast, lung etc.). Activation of these family members depends on their extracellular domains forming back-to-back hetero/homo dimers. Moreover, dimers are glycosylated, which is a crucial post-translational modification that affects the conformation and function of the protein. Here, molecular modeling and molecular docking are used to comprehensively investigate the dimerization mechanism in glycosylated back-to-back active dimer formation in the entire ErbB receptors for the first time. Results showed that 21 out of 37 clusters of active back-to-back dimers formed by all family members are through heterodimerization. Including; ErbB1-ErbB3/ErbB4, ErbB2-ErbB3/ErbB4 and ErbB3-ErbB4. Ranking ErbB2-ErbB3 as the most stabilized back-to-back dimeric construct. While glycan arrangements favor both homo/hetero dimerization at the dimeric interfaces, it promotes heterodimerization by stabilizing and packing the ligand binding sites of EGFR and ErbB2 respectively. These findings pave the path to future heterodimeric interface/glycan targeting rational anti-cancer drug designs for ErbB receptors.

The most often diagnosed and fatal malignancy in women is breast cancer. The International Agency for Research on Cancer (IARC) estimates that there are 2.26 million new cases of cancer in 2020. Adoptive cell therapy using T cells with chimeric antigen receptor shows potential for the treatment of solid tumors, such as breast cancer. In this work the effectiveness of CAR-T cells against monolayer and three-dimensional bioprinted tumor-like structures made of modified MCF-7 breast cancer cells was assessed. The cytokine profile of supernatants after co-cultivation of MCF-7 tumor cell models with CAR-T cells was also measured to reveal the inflammatory background associated with this interaction.