Search

Recent research indicates that mesenchymal stem cells (MSCs), known for their anti‐inflammatory and anti‐infectious properties, could be a promising alternative for treating inflammatory diseases such as inflammatory bowel disease (IBD). This study examined how MSCs and their derivatives, when cocultured with interleukin‐1β (IL‐1β)‐stimulated Caco‐2 cells, affect the expression of genes related to inflammation, microbes, and apoptosis. In the experiment, Caco‐2 cells were exposed to 10 ng/mL of IL‐1β for 24 h. MSCs were sourced from human bone marrow, adipose tissue (AD‐MSC), and menstrual blood. These MSCs and their conditioned medium (CM) were then cocultured with the IL‐1β‐induced Caco‐2 cells. After 48 h, gene expression levels were analyzed using real‐time PCR, and the data were statistically evaluated using T‐tests, U‐Mann–Whitney, and Tukey's post hoc analyses. The results indicated that IL‐1β at 10 ng/mL was the optimal concentration for inducing Caco‐2 cells with the highest viability and minimal damage. Among the MSCs tested, AD‐MSCs were the most effective in regulating gene expression. Specifically, AD‐MSC treatment significantly reduced the mRNA expression of TNF‐α and IL‐1β, both of which are crucial in sustaining inflammatory responses (p ≤ 0.05). This study concludes that AD‐MSCs have superior effects compared to other MSC sources in modulating genes associated with inflammation, antibacterial effects, and apoptosis in an in vitro model of IBD using Caco‐2 cells. [ABSTRACT FROM AUTHOR]

Patients with non-obstructive azoospermia (NOA) are unable to have their children. Therefore, there is an urgent need for additional treatment alternatives for these patients. Recently, novel treatments based on the exosomes derived from mesenchymal stem cells (MSCs) as the agents responsible for exerting the paracrine effects and consequently biological functions of MSCs are proposed. Besides, platelet-rich plasma (PRP) as a significant blood byproduct has been therapeutically applied in several male infertility studies. In this study, we compared the effects of PRP and exosome treatment on spermatogenesis restoration in NOA rat models. Exosomes and PRP were isolated from the adipose tissue-derived MSCs (AD-MSCs) collected from conditioned medium and peripheral blood of human volunteers, respectively. Non-obstructive azoospermia (NOA) induction was done through two doses of busulfan at a 21-day interval. Thirty-five days after NOA induction, intratesticular injection of AD-MSCs-derived exosome (AD-Exo), PRP, and PBS was performed. The control group did not receive any treatment. Two months later, the rats were euthanized for further analysis. Our results revealed that both AD-Exo and PRP treatments improved the size and weight of testis, modulated the expression level of Dazl, Ddx4, Stra8, Pwil1, and Ccna1, and ameliorated the serum level of LDH, SOD, and GR enzymes in NOA rats. Moreover, the AD-Exo group showed improved testosterone, GPx, MAD, and CAT serum levels, sperm motility, and protein levels of DAZL and DDX4. This investigation verified the more efficient effects of AD-Exo treatment in comparison to PRP in ameliorating busulfan-induced NOA rat models. [ABSTRACT FROM AUTHOR]

Breast cancer is a heterogenous disease, considered as the most common malignancy in women worldwide. Despite all efforts on identifying cancer, there is no definite therapy yet and much more attempts in discovering cancer biology seems necessary. Immunology of tumors declares the relevance of immune system, chronic inflammation and cancer. Many studies have supported the role of NF-κB in linking inflammation and tumorigenesis. NF-κB as an important actor of Inflammation, plays diverse roles in cancer. microRNAs have been implicated in a number of diseases including a broad range of cancers. miR-590 has been reported to regulate different pathways and affect different types of cancers. Objectives: Regarding that miR-590 plays various roles in different cells and it is down regulated in many cancer cells, we decided to transfect it in MDA-MB-231 (highly invasive) and MCF-7 (poor invasive) cells and trace the expression of NF-κB as an effective gene in cancer cells. The effect of miR-590 transfection in breast cancer cell lines on the expression of NF-κB was evaluated in this study. Materials and Methods: The primer for miR-590 was designed and used for PCR. The PCR product was extracted and the miRNA gene was cloned into the vector. miR-590-pLenti-III-eGFP vector was transfected into the breast cancer cells. 72 hours after transfection, the expression of miR-590 and NF-κB were measeured by qRT-PCR. Results: miR-590 was over-expressed as it was expected to occur and NF-κB level showed significant increase 72 hours after miRNA transfection in both cell lines. Conclusion: In this study, the sudden and redundant increase of NF-κB followed by miR-590 transfection in breast cancer cells was seen. It seems that miR-590 regulates NF-κB expression directly or indirectly. miR-590 sounds to be an effective regulatory factor in breast cancer which requires more studies to investigate its function on cancer and inflammation. [ABSTRACT FROM AUTHOR]

Breast cancer is the most frequent cancer among women worldwide. Tumor immunology suggests relationships between the immune system, chronic inflammation, and cancer. The immune system may either prevent or promote carcinogenesis. Here, we evaluated molecular signaling pathways common in inflammation and cancer and detected the microRNAs which play pivotal roles in mediating these pathways. Using bioinformatics assays, signaling pathways common in inflammation and cancer, and microRNAs mediating these pathways were identified. MiR-590 was selected and cloned into the pLenti-III-eGFP vector and transfected into the breast cancer cell lines. The expression level of microRNA and the candidate genes was evaluated by real-time quantitative reverse transcription polymerase chain reaction, and the apoptosis level in transfected cells was measured by Annexin V-7AAD assay. The cell migration was tested by real-time quantitative reverse transcription polymerase chain reaction for MMP2/MMP9. The expression levels of miR-590 and the selected genes (i.e. JAK2, PI3K, MAPK1, and CREB) were measured 72 h after transfection. While miR-590 showed an over-expression, the genes were significantly down-regulated. A significant increase was observed in apoptosis level in both cell lines and MMP2/MMP9 was significantly decreased in MDA-MB-231 cells. MiR-590 was selected as a microRNA which triggers and down-regulates critical genes of signaling pathways similar in cancer and inflammation. Following the miR-590 treatment, JAK2, PI3K, MAPK1, and CREB were down-regulated and the apoptosis level was increased in breast cancer cell lines. Apparently, some microRNAs can be good candidates for novel treatments of cancer. Although miR-590 showed good results in this study, further studies are required to investigate the role of miR-590 in breast cancer therapy. [ABSTRACT FROM AUTHOR]

Background: Cyclooxygenase 2 is a key enzyme which converts arachidonic acid into prostaglandins. Cyclooxygenase 2 is triggered by inflammatory stimuli, such as cytokines. Its expression increases in tumors and Alzheimer's disease and ovarian hyperstimulation syndrome. Polycystic ovarian syndrome is a heterogeneous disease characterized by pathological angiogenesis and chronic anovulation. In the present study, the probable role of cyclooxygenase 2 in Wistar rats with polycystic ovarian syndrome was investigated. Methods: Thirty female Wistar rats (170-200 gr) were equally divided into three groups: 2 mg estradiol valerate was intramuscularly administered to each rat in the experiment group or group 1; the rats in group 2 were regarded as the sham group and received sesame oil injections and group 3 or the control group received no injections. After 60 days of treatment, animals were anaesthetized with chloroform and killed by decapitation. Ovaries were collected for histological and immunohistochemical evaluations. All the experiments were repeated three times. Results: Morphologically, ovaries from the control group exhibited follicles in various stages of development and many fresh corpus luteum. In estradiol valerate group small follicles in early development were observed in addition to follicles showing evidence of atresia and many large cysts with thickened theca cell layer. Corpus luteum was rare or absent in group 2. The immunohistochemical analysis for cyclooxygenase 2 expression showed an increased expression of cyclooxygenase 2 enzyme in group 1. Conclusion: The results suggested the involvement of cyclooxygenase 2 in the progression to polycystic ovarian syndrome in a rat model. [ABSTRACT FROM AUTHOR]

Background: Photodynamic therapy (PDT) is a promising new cancer treatment strategy which inactivates tumor cells by simultaneoulsy using light and a photosensitizer. The similarity between tumors and newly implanted embryos is notable. Extrauterine pregnancy (EUP) does not have a definite treatment and previous therapeutic options (medical and surgical) have not been effective or suitable. Therefore, PDT is suggested as a possible treatment for EUP. Materials and Methods: The photosensitizer, hematoporphyrin, was injected locally into the placenta of one selected embryo from a pregnant Wistar rat (E15). Then, a laser beam was illuminated at the same point and 48 hours later, changes in the embryo and placenta were investigated. Furthermore, the integrity of the uterus was examined by macroscopic evaluation and sonographic images. Results: Sections obtained from treated and control groups demonstrated that the embryo and placenta were damaged in the PDT group, whereas the control ones were intact. Furthermore, macroscopic observations and sonographic images during the second parturition after treatment showed that the uterus was intact and fertility was preserved. Conclusion: Successful ablation of the treated embryo with no clear damage to the uterus attests to the success of this approach. The successful use of hematoporphyrin, as a first generation photosensitizer, should be further investigated for its possible clinical applications. [ABSTRACT FROM AUTHOR]

Objective: There are several factors, like environmental agents, neurotrophic factors, serotonin and some hormones such as estrogen, affecting neurogenesis and neural differentiation. Regarding to importance of proliferation and regeneration in central nervous system, and a progressive increase in neurodegenerative diseases, cell therapy is an attractive approach in neuroscience. The aim of the present study was to investigate the effects of sex steroid hormones and basic fibroblast growth factor (bFGF) on neuronal differentiation of mouse bone marrow-derived mesenchymal stem cells (BM-MSCs). Materials and Methods: This experimental study was established in Kharazmi University. BM was isolated from the bones of femur and tibia of 4-6-week old Naval Medical Research Institute (NMRI) mice, and the cells were cultured. The cells were divided into following 4 groups based on the applied treatments: I. control (no treatment), II. steroid hormones (β-estradiol, progesterone and testosterone), III. bFGF and IV. combination of steroid hormones and bFGF. Immunocytochemistry and flow cytometery analyses were applied for beta III-tubulin (β-III tubulin) and microtubule-associated proteins-2 (MAP-2) in 4 days of treatment for all groups. Results: The cells treated with combination of bFGF and steroid hormones represented more expressions of neural markers as compared to control and to other two groups treated with either bFGF or steroid hormones. Conclusion: This study showed that BM-MSCs can express specific neural markers after receiving bFGF pretreatment that was followed by sex steroid hormones treatment. More investigations are necessary to specify whether steroid hormones and bFGF can be considered for treatment of CNS diseases and disorders. [ABSTRACT FROM AUTHOR]

Long noncoding RNAs (lncRNAs) are prominent as crucial regulators of tumor establishment and are repeatedly dysregulated in multiple cancers. Therefore, lncRNAs have been identified to play an essential function in carcinogenesis and progression of cancer at genetic and epigenetic levels. FENDRR (fetal-lethal noncoding developmental regulatory RNA) as a LncRNA is a hallmark of various malignancies. FENDRR is crucial for multiple organs' development, such as the lung and heart. The effects of FENDRR under signaling pathways in different cancers have been identified. In addition, it has been verified that FENDRR can affect the development and progression of various cancers. In addition, FENDRR expression has been associated with epigenetic regulation of target genes participating in tumor immunity. Furthermore, FENDRR downregulation was observed in various types of cancers, including colorectal cancer, gastric cancer, pancreatic cancer, cholangiocarcinoma, liver cancer, gallbladder cancer, lung cancer, breast cancer, endometrial cancer, prostate cancer, chronic myeloid leukemia, osteosarcoma, and cutaneous malignant melanoma cells. Here, we review the biological functions and molecular mechanisms of FENDRR in several cancers, and we will discuss its potential as a cancer biomarker and as a probable option for cancer treatment., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Crohn's Disease (CD), which usually leads to anal fistulas among patients, is the most important inflammatory bowel disease that causes morbidity in many people around the world. This review article proposes using MSCs as a hopeful therapeutic strategy for CD and anal fistula treatment in both preclinical and clinical conditions. Finally, darvadstrocel, a cell-based medication to treat complex anal fistulas in adults, as the only European Medicines Agency (EMA)-approved product for the treatment of anal fistulas in CD is addressed. Although several common therapies, such as surgery and anti-tumor necrosis factor-alpha (TNF-α) drugs as well as a combination of these methods is used to improve this disease, however, due to the low effectiveness of these treatments, the use of new strategies with higher efficiency is still recommended. Cell therapy is among the new emerging therapeutic strategies that have attracted great attention from clinicians due to its unique capabilities. One of the most widely used cell sources administrated in cell therapy is mesenchymal stem cell (MSC). This review article will discuss preclinical and clinical studies about MSCs as a potent and promising therapeutic option in the treatment of CD and anal fistula., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Breast cancer is the most frequent cancer among women worldwide. Tumor immunology suggests relationships between the immune system, chronic inflammation, and cancer. The immune system may either prevent or promote carcinogenesis. Here, we evaluated molecular signaling pathways common in inflammation and cancer and detected the microRNAs which play pivotal roles in mediating these pathways. Using bioinformatics assays, signaling pathways common in inflammation and cancer, and microRNAs mediating these pathways were identified. MiR-590 was selected and cloned into the pLenti-III-eGFP vector and transfected into the breast cancer cell lines. The expression level of microRNA and the candidate genes was evaluated by real-time quantitative reverse transcription polymerase chain reaction, and the apoptosis level in transfected cells was measured by Annexin V-7AAD assay. The cell migration was tested by real-time quantitative reverse transcription polymerase chain reaction for MMP2/MMP9. The expression levels of miR-590 and the selected genes (i.e. JAK2, PI3K, MAPK1, and CREB) were measured 72 h after transfection. While miR-590 showed an over-expression, the genes were significantly down-regulated. A significant increase was observed in apoptosis level in both cell lines and MMP2/MMP9 was significantly decreased in MDA-MB-231 cells. MiR-590 was selected as a microRNA which triggers and down-regulates critical genes of signaling pathways similar in cancer and inflammation. Following the miR-590 treatment, JAK2, PI3K, MAPK1, and CREB were down-regulated and the apoptosis level was increased in breast cancer cell lines. Apparently, some microRNAs can be good candidates for novel treatments of cancer. Although miR-590 showed good results in this study, further studies are required to investigate the role of miR-590 in breast cancer therapy.