Search

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer (BC) that currently lacks specific therapy options. Thus, chemotherapy continues to be the primary treatment, and developing novel targets is a top clinical focus. The androgen receptor (AR) has emerged as a therapeutic target in a subtype of TNBC, with substantial clinical benefits shown in various clinical studies. Numerous studies have shown that cancer is associated with changes in components of the cell cycle machinery. Although cell cycle cyclin-dependent kinase (CDK) 4/6 inhibitors are successful in the treatment of ER-positive BC, they are not helpful in the treatment of patients with TNBC. We investigated the possibility of combining CDK4/6 inhibitor(ribociclib) with AR inhibitor(enzalutamide) in the AR-positive TNBC cell line. Ribociclib showed an inhibitory effect in TNBC cells. Additionally, we found that enzalutamide reduced cell migration/invasion, clonogenic capacity, cell cycle progression, and cell growth in AR-positive cells. Enzalutamide therapy could increase the cytostatic impact of ribociclib in AR+ TNBC cells. Furthermore, dual inhibition of AR and CDK4/6 demonstrated synergy in an AR+ TNBC model compared to each treatment alone. [ABSTRACT FROM AUTHOR]

Background: Breast cancer is one of the most prevalent types of cancer in Iranian women and the second cause of death in women worldwide. Gene mutations are the key determinants of the disease; therefore, the genetic study of this disease is of paramount importance. One of the genetic evaluation methods of this disease is microarray technology, which allows the examination of the simultaneous expression of thousands of genes. Clustering is the method for analyzing high-dimension data, which we used in the present research for collecting similar genes in separated clusters. Method: A descriptive and inferential statistical analysis was carried out to evaluate unsupervised learning models of gene expression analysis and five bi-clustering methods (including PLAID (PL), Fabia, Bimax, Cheng & Church (CC), and Xmotif) were compared. For this purpose, we obtained the microarray gene expression data for lapatinib-resistant breast cancer cell lines from previously published research. The enrichment efficacy of the clusters was evaluated with gene ontology, and the results of these five models were compared with the Jaccard index, variance stability, least-square error, and goodness of fit indices. Furthermore, the results of the best model were assessed for building a genes sets network with Bayesian networks. Results: After preprocessing, clustering was performed on the data with the dimension (4710 x 18) of the genes. Four models, except for CC, successfully found bi-clusters in the data set. The data evaluation revealed that the results of the models were almost the same, but the PL model performed better than the others, finding 11 bi-clusters; this model was used to build the network of gene sets. Conclusion: According to the results, the PL method was suitable for clustering the data. Accordingly, it could be recommended for data analysis. In addition, the gene sets network formed on gene expression data was incompetent. [ABSTRACT FROM AUTHOR]

Mesenchymal stem cells (MSCs) are earmarked as perfect candidates for cell therapy and tissue engineering due to their capacity to differentiate into different cell types. However, their potential for application in regenerative medicine declines when the levels of the reactive oxygen and nitrogen species (RONS) increase from the physiological levels, a phenomenon which is at least inevitable in ex vivo cultures and air‐exposed damaged tissues. Increased levels of RONS can alter the patterns of osteogenic and adipogenic differentiation and inhibit proliferation, as well. Besides, oxidative stress enhances senescence and cell death, thus lowering the success rates of the MSC engraftment. Hence, in this review, we have selected some representatives of antioxidants and newly emerged nano antioxidants in three main categories, including chemical compounds, biometabolites, and protein precursors/proteins, which are proved to be effective in the treatment of MSCs. We will focus on how antioxidants can be applied to optimize the clinical usage of the MSCs and their associated signaling pathways. We have also reviewed several paralleled properties of some antioxidants and nano antioxidants which can be simultaneously used in real‐time imaging, scaffolding techniques, and other applications in addition to their primary antioxidative function. [ABSTRACT FROM AUTHOR]

In situations where the molecular mechanism of many ocular disorders is unknown, owing to the difficulties associated with sampling from ocular tissues, human tear film can be a promising medium in ophthalmic research. The present study demonstrates an in-depth gel-based proteome optimization survey to approach more appropriate and efficient systems in various situations such as normal and dry-eye syndromes. Therefore, systematic and statistical evaluations were performed on different preparation methods, including acetone, acetone-methanol, chloroform-methanol-water, trichloroacetic acid (TCA)-acetone, tri- n-butylphosphate-acetone-methanol precipitations and ammonium sulfate fractionation at three different percentages of saturations (50, 70 and 90%). Methods were compared quantitatively on both one- and two-dimensional patterns. Some important parameters such as total protein recovery yield, densitometric analysis of some protein contaminants, banding patterns and total spot numbers along with statistical models for proper clustering were considered. Findings revealed noticeable impacts of preparation methods on all aspects of gel-based separations as well as recovery yield (ranging from 5.29 ± 0.96 to 22.56 ± 1.77 µg/mm) and banding and pattern resolution. In addition to all these, the most important point is that the total protein spot number on the final two-dimensional patterns (varied from 528.00 ± 19.00 to 657.00 ± 21.52 for different methods) were also noticeably increased in comparison with previously published reports (maximum of 250 spots), which is essential for a more comprehensive analysis. Increasing the proteome coverage in the present study is supposed to originate from improved solubility and effective rehydration during the sample application and isoelectric focusing (IEF) procedure along with proper sample preparation. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Objective. Sulfur mustard (SM) is a highly reactive alkylating agent which produces ocular, respiratory, and skin damages. Eyes are the most sensitive organ to SM due to high intrinsic metabolic and rapid turnover rate of corneal epithelium and aqueous-mucous interfaces of the cornea and conjunctiva. Here we investigate underlying molecular mechanism of SM exposure delayed effects which is still a controversial issue after about 30 years. Materials and Methods. Following ethical approval, we have analyzed serum proteome of ten severe SM exposed male patients with delayed eye symptoms with two-dimensional electrophoresis followed by matrix-assisted laser desorption/ionization time-of-flight/time-of-flight mass spectrometry. The western blotting was used to confirm the proteins that have been identified. Results. We have identified thirteen proteins including albumin, haptoglobin, and keratin isoforms as well as immunoglobulin kappa chain which showed upregulation while transferrin and alpha 1 antitrypsin revealed downregulation in these patients in comparison with healthy control group. Conclusions. Our results elevated participation of free iron circulatory imbalance and local matrix-metalloproteinase activity in development of delayed ocular symptoms induced by SM. It demonstrates that SM induced systemic toxicity leads to some serum protein changes that continually and gradually exacerbate the ocular surface injuries. [ABSTRACT FROM AUTHOR]

Thirty-eight different milk and milk powder samples from Tehran-Iran were collected and analyzed for Sr activity using a method in which the daughter product of Sr decay (Y) was extracted by tributyl phosphate from ashed milk. Y was then back extracted with water, and oxalate was precipitated . Following the sample analyzing, beta counting was performed with an ultralow-level liquid scintillation spectrometer. The quality control and assurance of the method were obtained by standard samples prepared with an IAEA-certified reference material. The mean determined Sr activity concentration in the analyzed milk and milk powder (0.225 ± 0.042 and 0.216 ± 0.024 Bq kg, respectively) showed that the radioactivity concentration in our samples was too low to induce biological hazards. These data can provide useful information of the background level of contamination, which in turn can be used in the following environmental monitoring programs. [ABSTRACT FROM AUTHOR]

Evaluating the effectiveness of drugs on an individual basis before prescribing them has an influential role in choosing a successful treatment plan. The advent of microfluidic devices has provided us with more real platforms capable of mimicking the natural microenvironment (scales, shear stress, diffusion transport, etc.). This research has introduced a truncated microfluidic gradient maker that can create a linear concentration gradient of trastuzumab (showing good correlation (r(9) = 0.9968) with simulation data) with a wide range of flow rates (20–190 µl/min) and investigate its effect on SK-BR-3 spheroid cells. The results of trastuzumab efficacy on 3D spheroid cells in the microchip were compared with the conventional 2D cell cultured by MTT assay at 24 h, 48 h, and 72 h. The results showed that trastuzumab had dose-dependent effects in both 2D and spheroid cell cultures. However, the IC50 values for trastuzumab were significantly higher in 2D cell culture (560 ± 23 µg/mL) compared to 3D spheroid models (407 ± 17 µg/mL). Moreover, compared with conventional drug sensitivity tests, this microchip required fewer samples and reagents and a lower risk of fluctuation and contamination due to automatic medium exchange. [Display omitted] • A novel truncated microfluidic chip which can generate nine different dosages of the drug in a smaller design was constructed. • Effects of the different dosages of trastuzumab on SK-BR-3 spheroids were observed. • The performance of trastuzumab on SK-BR-3 spheroids cultured in chip and 2d conventional model was compared. [ABSTRACT FROM AUTHOR]

• MERS-CoV, SARS-CoV-1/2 as members of β-CoVs family have many similar pathogenicity. • Frequency of emerging β-CoVs infections reported in males are higher than females. • Sex-hormones and X-chromosome related genes may be the cause of these sex differences. • Immune response of women might protect further against MERS, SARS-CoV1/2 infections. • Sex-based immune-responses may provide new insights for upcoming immunotherapies. Emerging beta-coronaviruses (β-CoVs), including Severe Acute Respiratory Syndrome CoV-1 (SARS-CoV-1), Middle East Respiratory Syndrome-CoV (MERS-CoV), and Severe Acute Respiratory Syndrome CoV-2 (SARS-CoV-2, the cause of COVID19) are responsible for acute respiratory illnesses in human. The epidemiological features of the SARS, MERS, and new COVID-19 have revealed sex-dependent variations in the infection, frequency, treatment, and fatality rates of these syndromes. Females are likely less susceptible to viral infections, perhaps due to their steroid hormone levels, the impact of X-linked genes, and the sex-based immune responses. Although mostly inactive, the X chromosome makes the female's immune system more robust. The extra immune-regulatory genes of the X chromosome are associated with lower levels of viral load and decreased infection rate. Moreover, a higher titer of the antibodies and their longer blood circulation half-life are involved in a more durable immune protection in females. The activation rate of the immune cells and the production of TLR7 and IFN are more prominent in females. Although the bi-allelic expression of the immune regulatory genes can sometimes lead to autoimmune reactions, the higher titer of TLR7 in females is further associated with a stronger anti-viral immune response. Considering these sex-related differences and the similarities between the SARS, MERS, and COVID-19, we will discuss them in immune responses against the β-CoVs-associated syndromes. We aim to provide information on sex-based disease susceptibility and response. A better understanding of the evasion strategies of pathogens and the host immune responses can provide worthful insights into immunotherapy, and vaccine development approaches. [ABSTRACT FROM AUTHOR]

Among different types of breast cancers (BC), triple-negative BC (TNBC) amounts to 15% to 20% of breast malignancies. Three principal characteristics of TNBC cells are (i) extreme aggressiveness, (ii) absence of hormones, and (iii) growth factor receptors. Due to the lack or poor expression of the estrogen receptor, human epidermal growth factor receptor 2, and progesterone receptor, TNBC is resistant to hormones and endocrine therapies. Consequently, chemotherapy is currently used as the primary approach against TNBC. Expression of androgen receptor (AR) in carcinoma cells has been observed in a subset of patients with TNBC; therefore, inhibiting androgen signaling pathways holds promise for TNBC targeting. The new AR inhibitors have opened up new therapy possibilities for BC patients carrying AR-positive TNBC cells. Our group provides a comprehensive review of the structure and function of the AR and clinical evidence for targeting the cell's nuclear receptor in TNBC. We updated AR agonists, inhibitors, and antagonists. We also presented a new era of genetic manipulating CRISPR/Cas9 and nanotechnology as state-of-the-art approaches against AR to promote the efficiency of targeted therapy in TNBC. SIGNIFICANCE STATEMENT: The lack of effective treatment for triple-negative breast cancer is a health challenge. The main disadvantages of existing treatments are their side effects, due to their nonspecific targeting. Molecular targeting of cellular receptors, such as androgen receptors, increased expression in malignant tissues, significantly improving the survival rate of breast cancer patients., (Copyright © 2023 by The American Society for Pharmacology and Experimental Therapeutics.)

Background: The unique expression pattern of prostate stem cell antigen (PSCA) in a number of prevalent neoplasms has made the antigen a great target for cancer researches, and many clinical methods have been developed based on the application of this tumor marker. Hence, optimal PSCA laboratory production can be considered a hallmark for many researchers., Objective: An analytical study was designed to improve the quality and quantity of PSCA production., Materials and Methods: The effects of different compositions of lysis buffers and some ultrasound durations were assessed by calculation of the protein recovery followed by PSCA specific blotting experiments. Then, based on the results of the web-based characterization, interference removal, followed by re-solubilization of the protein in various buffers, was designed, applied, and assessed., Results: Since the selection of an appropriate methodology depends merely on the research purposes, we tried to discuss the pros and cons of the investigated methods according to the hydrophobic nature of PSCA as well as its dramatic tendency to aggregate in the form of inclusion bodies in the expression hosts., Conclusions: We introduced a newly designed method to fit the delicate immunological surveys and overcome some limiting factors in PSCA production., (Copyright: © 2021 The Author(s); Published by Iranian Journal of Biotechnology.)