Stem cells and exosomes: as biological agents in the diagnosis and treatment of polycystic ovary syndrome (PCOS)

A typical condition of the female reproductive system is polycystic ovary syndrome (PCOS). Hyperinsulinemia, insulin resistance, obesity, and hyperandrogenism are just a few of the metabolic abnormalities linked to this disease. Type 2 diabetes, hypertension, and cardiovascular disease are further issues related to PCOS. One consequence of this syndrome for which numerous treatment procedures have been developed is infertility. Metformin and clomiphene, two common allopathic medications used to treat PCOS, both have drawbacks and are ineffective. It is vital to seek novel therapeutic modalities to address these constraints. Exosomes (EXOs) are a particular class of extracellular vesicles that cells release, and they are known to play a significant role in mediating intercellular communication. A wide range of cargo, including lipids, proteins, mRNA, miRNAs, and numerous other noncoding RNAs, are contained in the nanoscale lipid bilayer exosomes. The cytokine effects of stem cells and EXOs derived from them enable the defense against metabolic diseases like PCOS. Moreover, EXO microRNAs can potentially be employed as biomarkers in the detection and management of PCOS. In this study, the potential of stem cells and exosomes are specifically investigated in the diagnosis and treatment of PCOS as one of the diseases of the female reproductive system

An overview of current knowledge in biological functions and potential theragnostic applications of exosomes

Exosomes are cup-shaped structures, made of two lipid layers. Their size is in the range of 30–150 nm. Exosomes are excreted to the extracellular space and function in local and systemic cellular communication. Based on their primary origins, they can contain substantial amounts of RNA, protein, and miRNA; the horizontal transfer of these contents significantly determines the exosome's biological effects. The endosomal origins of exosomes can be deduced based on their surface protein markers. The use of exosomes as a diagnostic biomarker and therapeutic tool, has numerous advantages because they do not pose risks such as aneuploidy and transplant rejection. This - overview highlights the recent findings in exosome development and current knowledge in exosome-based therapies. Keywords:Extracellular vesicles, Exosomes, Clinical application

Characterization of the decellularized ovine pericardium for skin tissue engineering

Background and aims: Some biological scaffolds are used as appropriate skin substitutes, including decellularized amniotic membrane or dermis although the ovine pericardial tissue has not been characterized or used for skin tissue engineering. In this regard, this study focused on the decellularization and characterization of ovine pericardium for skin tissue engineering. Materials and Methods: To this end, two different methods were used for decellularization, including safety data sheet (SDS) 1% (method 1) and Triton X-100 1% (method 2). In addition, histological examinations (H&E staining), DNA content assay, scanning electron microscopy (SEM), MTT test using human adipose-derived mesenchymal stem cells, and tensile tests were conducted for sample characterization. Results: Based on the results, the DNA content showed significant DNA removing (P<0.001) after decellularization with methods 1 and 2 in comparison to native tissues although the significance level between the two methods was P=0.06. In the SEM examination, cells were effectively removed while the extracellular matrix remained intact in both groups. Based on the results of the MTT test, the toxicity was not significant (P=0.36). On the other hand, mechanical property assay revealed a higher value of Young’s modulus in method 1 (34.12 MPa) compared to Method 2 (32.57 MPa) and native tissues (30 MPa). Finally, the highest strain at the break point (approximately 0.6) belonged to the native sample. Conclusion: In general, the ovine seems to be a good alternative for skin tissue engineering and regeneration since it is a post-slaughtering waste tissue has low thickness, is wide and spread, and easy to be decellularized with SDS 1% and Triton X-100. Eventually, it has good properties for cell seeding based on the findings of our study and the capability of vascularization reported in the literature. Keywords: Ovine pericardium, Acellular, Skin tissue engineerin

Antiproliferative effects of fresh water crab hemolymph and meat extract on breast cancer cell line

&lt;strong&gt;Background and aims:&lt;/strong&gt; Despite the advances in drugs, side effects of chemotherapy drugs continue to exist. Therefore, more attention has been paid to the compounds derived from medicinal herbs and aquatic organisms. This study aimed to investigate the effect of freshwater crab hemolymph and meat extract on breast cancer (BC) cell line (4T1). &lt;strong&gt;Methods:&lt;/strong&gt; After isolation of freshwater crab hemolymph and meat extract, protein concentration and total antioxidant capacity were analyzed by bicinchoninic acid (BCA) and cupric reducing antioxidant capacity (CUPRAC) methods. The 4T1 cells and bone marrow mesenchymal stem cells (BMSCs) were treated with crab hemolymph (1, 2, 10 mg/mL) and meat extract (0.1, 0.2 and 1 mg/mL), and cell survival was analyzed using 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay (MTT) at 48 and 72 hours. Nitric oxide (NO) secretion was measured by Griess method. Data were analyzed using one-way analysis of variance (ANOVA). &lt;strong&gt;Results:&lt;/strong&gt; Protein concentration of 23.25 mg/mL was shown in crab hemolymph, and 2.3 mg/mL in meat extract. Total antioxidant capacity was reported as 1.036 µM/mL and 1.104 µM/mL in crab hemolymph and meat extract, respectively. Cell survival in the 4T1 cells was decreased in a dose- and time-dependent manner (&lt;em&gt;P&lt;/em&gt;�0.001). NO secretion of 4T1 cells was decreased after treatment with different concentrations of crab hemolymph and meat extract at 48 and 72 hours. Cellular growth was observed in BMSCs after treatment with different concentrations of crab hemolymph and meat extract at 48 and 72 hours. &lt;strong&gt;Conclusion:&lt;/strong&gt; Since crab hemolymph and meat extract have protein and antioxidant activities, they can have anti-cancer effects on 4T1 cells

Exploring the Behaviors of Tourists at Historical Sites Vandalism or Expression of Attachment Toward Place (A Case Study of Written Words on Si-o-Se-Pol Bridge)

Some tourists etch their names on the walls of historical buildings as a permanent mark without any significance. Sociologists refer to these individuals as vandals. This study discusses this topic from the perspective of environmental psychology and assumes that these scribbled written words are one of the signs of attachment to a place. Therefore, the research aims at examining the reasons why such behaviors occur to take a step towards controlling, reducing, and preventing destruction by tourists by writing or inscribing words. For this purpose, this research attempted to answer two questions: What motivates some tourists to leave written words on historical sites and monuments (such as the Si-o-se-pol bridge)? Which vandalistic motivations or sense of attachment to the place dominates this bridge? To analyze the data, the written words were categorized into groups (A.B.C.D), and a visible sense of attachment was observed in all of these groups. Qualitative content analysis was used to uncover hidden meanings. After studying the remaining written words on the bridge walls, semi-structured interviews (open-response) were carried out with vandal tourists. The results indicate that the written words are driven by a sense of attachment to the place. According to theoretical definitions, this type of behavior, recording memories with a name and date, reflects the feelings of people who have visited the place repeatedly

Evaluation of vacuum washing in the removal of SDS from decellularized bovine pericardium: method and device description.

AIMS: The aim of this study was to present a new method for removing Sodium dodecyl sulfate (SDS) detergent from decellularized bovine pericardium using vacuum. MATERIALS AND METHODS: The cows' pericardia were collected and decellularized. The samples were incubated with SDS1% for 48 h at 40 °C. To perform vacuum washing (VW: negative pressure was used to wash and remove detergents), every decellularized tissue was cut in 75mm diameter and fixed via a stainless-steel ring with 60mm diameter in the center of filtration Buchner Funnel which was connected to glass filtration flask The system was connected to a vacuum pump by a hose, and a negative pressure of -100 mmHg was applied for 15 min. Then, the samples were shaken and washed at 40-rpm in 100 ml of distilled water for 45 min. This process was repeated for samples of each group (6 times for sample VW6h, 12 times for sample VW12h, and 24 times for sample VW24h). At the end of every cycle, the effluent was collected to take a sample for SDS measurement. The normal washing (NW) group containing distilled water (NWd) and PBS (Phosphate buffered saline) (NWp) were used to wash and remove detergents. SDS measurements, MTT Assay, histological and tensile test, to compare two methods were used. RESULTS: The highest SDS in the effluent was in groups VW12h and VW24h (P ≤ 0.001) and the lowest residual SDS in scaffold was in two groups of VW12h and VW24h (P ≤ 0.001). MTT assay showed that cell survival in the VW12h and VW24h groups was higher than other groups and there' was no significant difference between cell survival in the VW12h and VW24h groups. Histological study showed destruction of tissue in the VW24h group. The results of the tensile test were shown that the native group had the highest module and the lowest amount was the VW24h sample which was reported with P ≤ 0.001 significance for all groups. CONCLUSION: VW12h can be used as an effective method for SDS removal from decellularized pericardium which morphologically demonstrated a good structure in ECM. KEYWORDS: Acellular; Cell biology; Cell culture; Cytotoxicity; Extracellular matrix; Pericardium; Regenerative medicine; Sodium dodecyl sulfate; Stem cells research; Toxicit

Exosomes: special nano-therapeutic carrier for cancers, overview on anticancer drugs

Chemotherapy drugs are the first line of cancer treatment, but problems such as low intratumoral delivery, poor bioavailability, and off-site toxicity must be addressed. Cancer-specific drug delivery techniques could improve the therapeutic outcome in terms of patient survival. The current study investigated the loading of chemotherapy drugs loaded into exosomes for cancer treatment. Exosomes are the smallest extracellular vesicles found in body fluids and can be used to transfer information by moving biomolecules from cell to cell. This makes them useful as carriers. As the membranes of these nanoparticles are similar to cell membranes, they can be easily transported to carry different components. As most chemotherapy drugs are not easily soluble in liquid, loading them into exosomes can be a suitable solution to this problem. This cancer treatment could avert the injection of high doses of drugs and provide a more appropriate release mechanism

Decellularized tissues as platforms for digestive system cancer models

The extracellular matrix (ECM) is a multifunctional network of macromolecules that regulate various cellular functions and physically support the tissues. Besides physiological conditions, the ECM also changes during pathological conditions such as cancer. As tumor cells proliferate, notable changes occur in the quantity and makeup of the surrounding ECM. Therefore, the role of this noncellular component of tissues in studies of tumor microenvironments should be considered. So far, many attempts have been made to create 2-dimensional (2D) or 3-dimensional (3D) models that can replicate the intricate connections within the tumor microenvironment. Decellularized tissues are proper scaffolds that imitate the complex nature of native ECM. This review aims to summarize 3D models of digestive system cancers based on decellularized ECMs. These ECM-based scaffolds will enable us to study the interactive communication between cells and their surrounding environment which brings new potential for a better understanding of the pathophysiology of cancer

Altered Expression of CD44, SIRT1, CXCR4, miR-21, miR-34a, and miR-451 Genes in MKN-45 Cell Line After Docetaxel Treatment

Purpose: Today it is known that the gene expression profile of cancer stem cells differs from other cancer cells, which may lead to the resistance to routine treatments. The aim of this study was to investigate the effect of docetaxel (DOC) treatment on CD44+ cell frequency in human gastric cancer (GC) MKN-45 cell line and its effect on expression levels of SIRT1, CXCR4, microRNA (miR)-21, miR-451, and miR-34a that are closely correlated with the chemoresistance or self-renewal of cancer stem cells (CSCs). Methods: The cytotoxic effect of DOC on MKN-45 cell line was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT)-assay. The frequency of CD44+ cells was measured by flow cytometry in the treated and control groups. The expression level of SIRT1, CXCR4, miR-21, miR-451, and miR-34a was assessed in DOC-treated and non-treated cells using quantitative real-time PCR. Data were analyzed using Statistical Package for the Social Sciences (SPSS) software. Results: The half-maximal inhibitory concentration (IC50) of DOC was 10 μg/ml after 48 h. Flow cytometry showed a significant increase in CD44+ cells after treatment with DOC (94.3) when compared with non-treated cells (84.6) (P &lt; 0.01). The expression of SIRT1, CXCR4, and miR-21 was up-regulated (1.4-fold, 6.7-fold, and 1.22-fold, respectively, P &lt; 0.05) in DOC-treated cells relative to non-treated cells, while miR-451 and miR-34a were down-regulated (0.14-fold and 0.36-fold, respectively, P &lt; 0.05). Conclusion: DOC treatment affected CD44+ cell frequency in MKN-45 cell line and induced significant changes in the expression of SIRT1, CXCR4, miR-21, miR-451, and miR-34a that are implicated in stemness and chemo-radioresistance, which might offer new insights for future GC therapies

A Study on COVID-19 Recurrence in Patients Discharged from Hospital: Narrative Review

Background & Objective: The 2019 coronavirus disease (COVID-19) is a highly contagious disease that has affected people in several countries around the world. COVID‐19 has been announced a pandemic by the World Health Organization (WHO). Unfortunately, in some cases, COVID-19 diagnosis tests are confirmed positive again after the recovery of patients and or discharge from the hospital. This study aimed to evaluate the symptoms of patients in whom coronavirus testing was recurrent positive. Materials & Methods: The search was conducted in articles from electronic and scientific literature databases such as Pub Med, EMBASE, Scopus and Medline, published from January 2020 to August 2020 using keywords of COVID-19, Recurrent Positive, Readmitted, Novel Coronavirus, RT-PCR test. Results: Studies have shown that in some patients, after a coronavirus test is negative and after the patients are discharged from the hospital, the RT-PCR test is positive again without contact with another patient. Conclusion: Studies reported that in a small number of patients recovered from the COVID-19, the RT-PCR test is positive again. Various factors are involved in this process for example sampling method, sample processing, re-infection of patient, virus re-grow, patient's immune system and etc