PAMAM dendrimer roles in gene delivery methods and stem cell research

Nanotechnology has provided new technological opportunities, which could help in challenges confronting stem cell research. Polyamidoamine (PAMAM) dendrimers, a new class of macromolecular polymers with high molecular uniformity, narrow molecular distribution specific size and shape and highly functionalised terminal surface have been extensively explored for biomedical application. PAMAM dendrimers are also nanospherical, hyperbranched and monodispersive molecules exhibiting exclusive properties which make them potential carriers for drug and gene delivery

Induction of pluripotency in human umbilical cord mesenchymal stem cells in feeder layer-free condition

Induced Pluripotent Stem Cells (iPSCs) has been produced by the reprogramming of several types of somatic cells through the expression of different sets of transcription factors. This study consists of a technique to obtain iPSCs from human umbilical cord mesenchymal stem cells (UC-MSCs) in a feeder layer-free process using a mini-circle vector containing defined reprogramming genes, Lin28, Nanog, Oct4 and Sox2. The human MSCs transfected with the minicircle vector were cultured in iPSCs medium. Human embryonic stem cell (ESC)-like colonies with tightly packed domelike structures appeared 7–10 days after the second transfection. In the earliest stages, the colonies were green fluorescence protein (GFP)-positive, while upon continuous culture and passage, genuine hiPSC clones expressing GFP were observed. The induced cells, based on the ectopic expression of the pluripotent markers, exhibited characteristics similar to the embryonic stem cells. These iPSCs demonstrated in vitro capabilities for differentiation into the three main embryonic germ layers by embryoid bodies formation. There was no evidence of transgenes integration into the genome of the iPSCs in this study. In conclusion, this method offers a means of producing iPSCs without viral delivery that could possibly overcome ethical concerns and immune rejection in the use of stem cells in medical applications

Harnessing the TP53INP1/TP53I3 axis for inhibition of colorectal cancer cell proliferation through MEG3 and Linc-ROR Co-expression

Dysregulation of long noncoding RNAs (lncRNAs), such as maternally expressed gene 3 (MEG3) and long intergenic noncoding RNA regulator of reprogramming (linc-ROR), plays a crucial role in colorectal cancer progression. We aimed to assess linc-ROR silencing and MEG3 activation on the colorectal cancer cell proliferation simultaneously; and explore the underlying mechanisms in the TP53-associated Pathway.The MEG3 and linc-ROR shRNA were cloned under the bidirectional CEA promoter (UM1). Subsequently, additional vectors were constructed to express linc-ROR shRNA (UM2) and MEG3 (UM3). After transfecting colorectal cancer cell lines with these recombinant vectors, experiments on cell viability, apoptosis, and cell cycle analysis were conducted. Furthermore, TP53's transcriptional activity and associated genes were assessed using quantitative real-time polymerase chain reaction (qRT-PCR).Interestingly, UM1 significantly inhibited the proliferation of both cell lines than UM2 and UM3. In response to UM1, TP53 transcript remarkably increased in HCT116 cells (10.46) than SW480 cells (6.16); which resulted in up-regulation of TP53INP1, TP53I3, GDF15, CCKN1A and BAX, and down-regulation of G1 cyclins (D1, E1). The rate of apoptosis increased in HCT116 (36.35 %) and SW480 (16.64 %) cells than control. Moreover, UM1-transfected HCT116 cells exhibited a notable arrest in the G0/G1 phase, accompanied by a reduction in the G2/M cell population.Compared to unidirectional vectors, the concurrent targeting approach enhanced TP53 activation at the transcription level. The cell response to UM1 resulted in rapid upregulation of TP53, leading to inhibition of cell proliferation, increased apoptosis, and cell cycle arrest. These findings suggest that the synergistic effect of targeting both MEG3 and linc-ROR could serve as a promising therapeutic strategy for TP53-associated colon cancer

Composition for promoting lactation with tumour suppressive properties and preparation method thereof.

The present invention discloses a nutraceutical composition alone or in combination with other biological active ingredients that is capable of increasing milk production and suppressing tumour in human and other mammals, the composition comprises marine algae, particularly seaweed plant extract having anti-estrogenic property. The seaweed plant derived nutraceutiacal either alone or in combination with other galactogogues, provides the necessary nutrients to increase milk production in mammmals

Epidemiology of Gastrointestinal Cancers (Stomach, Esophageal and Colorectal) in Neyshabur City during 2006-2012

Introduction and Aims Gastrointestinal cancers (GI) are considered as the most common cancer among men and are the second in women. The aim of this study was to evaluate the changes in crude and age specific incidence rates of gastrointestinal cancers in Neyshabur during 2006-2012. Materials and Methods In this study the recorded data of Neyshabur’s patients with cancer in the hospitals of Mashhad and Neyshabur were analyzed using Excel and SPSS v.16. Crude and age specific incidence rates were also estimated. Results Three hundred and thirty-five (42.8%) out of all 783 patients with cancer, were GI cancers. Gastric cancer showed the highest prevalence (41.8%) with the rate of 63.3 and 36.7 percent in men and women respectively. The results indicated the incidence of gastric cancer had a falling tendency. Conclusion About half of all the cancers in Neyshabur are of the GI type and their incidence rate up to 2012 showed a decreasing trend so that, this rate is higher in men and older age groups. This decline may be due to numerous reasons such as control of risk factors, failure to identify eligible patients, referring to medical centers outside the province, or an increase in mortality and etc. that needs further investigation. * Corresponding Author: Mashhad University of Medical Sciences, Clinical Research Development Unit. Email: [email protected]

Prevalence of chlamydia psittaci in pigeons in Chaharmahal va Bakhtiari and Yazd provinces of Iran, by nested-PCR, 2012

Background and objectives: Chlamydia psittaci is an intracellular bacterium that may cause endemic avian chlamydios is and respiratory psittacosis in humans. Feral birds and domesticated poultry are considered as potential hosts. While feral pigeons in towns worldwide are commonly infected, infection may occur via inhalation of aerosols of dried infective avian excreta. The aim of this study was the determination of prevalence of C. psittaci in feces of pigeons in Chaharmahal va Bakhtiari and Yazd provinces in Iran using nested PCR.Material and Methods: Samples were collected from pigeons in bird shops, backyards or cages in houses. Eighty eight genomic DNAs were extracted from the samples with a DNA purification kit (CinnaGen Inc. Iran) according to the manufacturer’s instructions. Extracted DNA was tested to detect C. psittaci DNA by a nested genus- and species-specific PCR. Primers were designed to amplify 16s rRNA. The first pair of primers was specific for the genus, and the second pair was specific to the species of C. psittaci. Results: he average infection rate was about %52 (46 samples from 88 samples). Conclusion:T It shows that a relatively high percentage of pigeons were infected with C. psittaci and may be able to play an important role as a source of infection for human or other mammals. More studies should be done to find more information like predominant genotypes of C. psittaci in Iran

Induction of mammary gland tumor in female Sprague-Dawley rats with LA7 cells

The current methods for tumor induction in breast cancer research animal models are time-consuming, hazardous, expensive, sometimes irreproducible and inconvenient. We successfully developed a new, simple and cost-effective method in developing solid mammary gland tumor in female Sprague-Dawley rat using LA7 rat mammary tumor cells. Tumors developed in 7- 8 weeks old rats within 6 to 8 days of subcutaneous injection of LA7 cells into the mammary gland pad. Tumor size increased exponentially for four weeks. Histopathology examination confirmed that the induced tumors were adenocarcinomas. Evaluation of blood enzymes showed significantly higher (P < 0.005) serum alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) in tumor-bearing than in normal rats. This LA7 cell-induced rat mammary gland tumor model may be useful for studies in breast cancer drug or nutraceutical research and development

Enhancing protein production and growth in chinese hamster ovary cells through miR-107 overexpression

Abstract Chinese Hamster Ovary (CHO) cells are widely employed as host cells for biopharmaceutical production. The manufacturing of biopharmaceuticals poses several challenges, including restricted growth potential and inadequate productivity of the host cells. MicroRNAs play a crucial role in regulating gene expression and are considered highly promising tools for cell engineering to enhance protein production. Our study aimed to evaluate the effects of miR-107, which is recognized as an onco-miR, on erythropoietin-producing CHO cells (CHO-hEPO). To assess the impact of miR-107 on CHO cells, a DNA plasmid containing miR-107 was introduced to CHO-hEPO cells through transfection. Cell proliferation and viability were assessed using the trypan blue dye exclusion method. Cell cycle analysis was conducted by utilizing propidium iodide (PI) staining. The quantification of EPO was determined using an immunoassay test. Moreover, the impact of miR-107 on the expression of downstream target genes was evaluated using qRT-PCR. Our findings highlight and underscore the substantial impact of transient miR-107 overexpression, which led to a remarkable 2.7-fold increase in EPO titers and a significant 1.6-fold increase in the specific productivity of CHO cells (p < 0.01). Furthermore, this intervention resulted in significant enhancements in cell viability and growth rate (p < 0.05). Intriguingly, the overexpression of miR‑107 was linked to the downregulation of LATS2, PTEN, and TSC1 genes while concurrently driving upregulation in transcript levels of MYC, YAP, mTOR, and S6K genes within transgenic CHO cells. In conclusion, this study collectively underscores the feasibility of utilizing cancer-associated miRNAs as a powerful tool for CHO cell engineering. However, more in-depth exploration is warranted to unravel the precise molecular intricacies of miR-107's effects in the context of CHO cells

Upregulation of the c-MYC oncogene and adjacent long noncoding RNAs PVT1 and CCAT1 in esophageal squamous cell carcinoma

Abstract Background All cell types express long non-coding RNAs (lncRNAs), which have the potential to play a role in carcinogenesis by altering the levels of their expression. Squamous cell carcinoma of the esophagus (ESCC) is a deadly disease with a poor prognosis and a high frequency of lymphatic metastases. Understanding the functional role and signaling pathways of two neighboring lncRNAs, CCAT1 and PVT1, in this oncogene’s pathogenesis may help us determine ESCC. Furthermore, it is still unclear whether these lncRNAs are linked to the clinicopathological characteristics of patients with ESCC. Methods For this study, we used biopsy from the Imam Khomeini Cancer Institute’s tumor bank in Tehran, Iran to obtain 40 ESCC tumor samples and their normal margin counterparts. The expression levels of the CCAT1, PVT1, and c-MYC genes were assessed using quantitative Real-Time RT-PCR. Additionally, demographic data and clinical-pathologic characteristics, such as tumor grade, tumor stage, lymph node, and metastasis, were taken into consideration. Graphpad prism version 8 was used for bioinformatics analyses. Results Comparing ESCC tissues to non-tumor tissues, we found significant upregulation of PVT1, CCAT1, and c-MYC. Patients with ESCC who had increased PVT1 expression also had higher rates of advanced stage and lymph node metastasis, whereas increased CCAT1 expression was only linked to advanced stage and wasn’t associated with lymph node metastasis. In predicting ESCC, CCAT1 (p < 0.05) was found to be an important factor. Overall survival was reduced by c-MYC and PVT1 overexpression (p < 0.001), according to Kaplan-Meier analysis. PVT1, CCAT1, and c-MYC were found to interact with 23 miRNAs with high and medium score classes, as shown in a bioinformatics study. We summarized the experimentally proven interactions between c-MYC, PVT1, and CCAT1 and other miRNAs, lncRNAs, and proteins. Conclusion This is the first report that CCAT1, PVT1 and c-MYC have been found to be up-regulated simultaneously in ESCC. It is possible that these genes may be involved in ESCC as a result of these findings. Therefore, as consequence, more research is needed to determine whether or not these lncRNAs play an oncogenic role in ESCC development and progression, as well as the regulatory mechanisms that control them