Association between cytomegalovirus infection and neurological disorders: A systematic review.

Cytomegalovirus (CMV) belongs to the Herpesviridae family and is also known as human herpesvirus type 5. It is a common virus that usually doesn't cause any symptoms in healthy individuals. However, once infected, the virus remains in the host's body for life and can reactivate when the host's immune system weakens. This virus has been linked to several neurological disorders, including Alzheimer's disease, Parkinson's disease, Autism spectrum disorder, Huntington's disease (HD), ataxia, Bell's palsy (BP), and brain tumours, which can cause a wide range of symptoms and challenges for those affected. CMV may influence inflammation, contribute to brain tissue damage, and elevate the risk of moderate-to-severe dementia. Multiple studies suggest a potential association between CMV and ataxia in various conditions, including Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy, acute cerebellitis, etc. On the other hand, the evidence regarding CMV involvement in BP is conflicting, and also early indications of a link between CMV and HD were challenged by subsequent research disproving CMV's presence. This systematic review aims to comprehensively investigate any link between the pathogenesis of CMV and its potential role in neurological disorders and follows the preferred reporting items for systematic review and meta-analysis checklist. Despite significant research into the potential links between CMV infection and various neurological disorders, the direct cause-effect relationship is not fully understood and several gaps in knowledge persist. Therefore, continued research is necessary to gain a better understanding of the role of CMV in neurological disorders and potential treatment avenues.

Antitumor activity and phenolic profile of Melissa officinalis extract against human gastric adenocarcinoma cells.

Gastric cancer remains a global health concern, driving the exploration of natural products with anticancer potential. This study investigated the antiproliferative activity and chemical composition of a 70% ethanolic extract from Melissa officinalis L. against human gastric cancer cells. The extract was prepared and evaluated for total phenolic content, antioxidant capacity and flavonoid content. The MTT test checked how well it stopped the growth of human gastric adenocarcinoma (AGS) and normal dermal fibroblast (HDF) cells. Data analysis (SPSS Statistics) determined viable cell percentages and performed regression analysis (p<0.05). The extract exhibited significant antiproliferative activity against AGS cells compared to normal cells (p<0.05), with decreasing IC50 values (564.3, 258.0 and 122.5 µg/ml) over 24, 48 and 72 hours. It also displayed antioxidant activity (IC50=16.8±1.41µg/ml) and contained substantial phenolics (225.76±4.1 mg GAE/g) and flavonoids (22.36±2.6 mg RUT/g). This study suggests the 70% ethanolic extract of M. officinalis effectively suppresses AGS cell growth and possesses promising antioxidant properties, highlighting its potential as a natural source of anticancer and antioxidant agents, deserving further investigation.

Exosome loaded hydroxyapatite (HA) scaffold promotes bone regeneration in calvarial defect: an in vivo study.

In this study, hydroxyapatite (HA) scaffolds were synthesized and characterized, following the osteogenic and angiogenic effects of HA scaffolds with or without endometrial mesenchymal stem stromal cells (hEnSCs) derived Exosomes were investigated in rat animal model with calvaria defect. The X-ray diffraction (XRD) analysis of HA powder formation was confirmed with Joint Corporation of Powder Diffraction Standards (JCPDS) files numbers of 34-0010 and 24-0033A and Ball mill, and sintering manufactured Nano-size particles. Obtained results containing FE-SEM images presented that the surface of scaffolds has a rough and porous structure, which makes them ideal and appropriate for tissue engineering. Additionally, the XRD showed that these scaffolds exhibited a crystallized structure without undergoing phase transformation; meanwhile, manufactured scaffolds consistently release exosomes; moreover, in vivo findings containing hematoxylin-eosin staining, immunohistochemistry, Masson's trichrome staining, and histomorphometric analysis confirmed that our implant has an osteogenic and angiogenic characteristic. So prepared scaffolds containing exosomes can be proposed as a promising substitute in tissue engineering.

3D printed polylactic acid/gelatin-nano-hydroxyapatite/platelet-rich plasma scaffold for critical-sized skull defect regeneration.

BACKGROUND: Three-dimensional (3D) printing is a capable approach for the fabrication of bone tissue scaffolds. Nevertheless, a purely made scaffold such as polylactic acid (PLA) may suffer from shortcomings and be restricted due to its biological behavior. Gelatin, hydroxyapatite and platelet-rich plasma (PRP) have been revealed to be of potential to enhance the osteogenic effect. In this study, it was tried to improve the properties of 3D-printed PLA scaffolds by infilling them with gelatin-nano-hydroxyapatite (PLA/G-nHA) and subsequent coating with PRP. For comparison, bare PLA and PLA/G-nHA scaffolds were also fabricated. The printing accuracy, the scaffold structural characterizations, mechanical properties, degradability behavior, cell adhesion, mineralization, systemic effect of the scaffolds on the liver enzymes, osteocalcin level in blood serum and in vivo bone regeneration capability in rat critical-sized calvaria defect were evaluated. RESULTS: High printing accuracy (printing error of < 11%) was obtained for all measured parameters including strut thickness, pore width, scaffold density and porosity%. The highest mean ultimate compression strength (UCS) was associated with PLA/G-nHA/PRP scaffolds, which was 10.95 MPa. A slow degradation rate was observed for all scaffolds. The PLA/G-nHA/PRP had slightly higher degradation rate, possibly due to PRP release, with burst release occurred at week 4. The MTT results showed that PLA/G-nHA/PRP provided the highest cell proliferation at all time points, and the serum biochemistry (ALT and AST level) results indicated no abnormal/toxic influence caused by scaffold biomaterials. Superior cell adhesion and mineralization were obtained for PLA/G-nHA/PRP. Furthermore, all the developed scaffolds showed bone repair capability. The PLA/G-nHA/PRP scaffolds could better support bone regeneration than bare PLA and PLA/G-nHA scaffolds. CONCLUSION: The PLA/G-nHA/PRP scaffolds can be considered as potential for hard tissue repair.

The effect of Scrophularia striata on cell attachment and biocompatibility of decellularized bovine pericardia.

Since using tissue transplantation has faced limitations all over the world, regenerative medicine has introduced decellularized tissues as natural scaffolds and researchers are trying to improve their efficiency and function. In this study, to increase cell attachment and ultimately cell proliferation on decellularized bovine pericardia, scrophularia striata extract was used. Scrophularia striata is an Iranian traditional medicinal plant. For this aim after decellularization of bovine pericardium and analysis of its morphology, it was incubated in scrophularia striata solution. Next, isolated human adipose-derived mesenchymal stem cells were cultured on the tissue. Finally, MTT assay, nitric oxide assay, and scanning electron microscopy observation were performed. MTT showed an increase in cell survival after treating the tissue with the plant extract after 48 h in a dose dependent manner significantly. The survival of cells in 0.5%, 2.5%, and 5% groups was about 5, 10 and 15 folds higher in comparison to control groups, respectively. Additionally, nitric oxide secretion in 2.5% and 5% samples was three and five folds higher than that in control group, respectively. Moreover, SEM observation indicated an impressive and dose-dependent effect of using Scrophularia striata on tissue biocompatibility. The results of this study showed that using Scrophularia striata increased cell viability and cell attachment on decellularized pericardia which could pave the way for the use of natural extracts of medicinal plants to reduce unwanted effects and make desired changes in decellularized tissues.

Delivery of injectable thermo-sensitive hydrogel releasing nerve growth factor for spinal cord regeneration in rat animal model.

The main goal of this study was to explore the beneficial effect of nerve growth factor (NGF)-overexpressing of human adipose-derived mesenchymal stem cells (hADSCs) encapsulated in injectable chitosan/ß-glycerophosphate/hydroxyethylcellulose (CS/ß-GP/HEC) hydrogel for spinal cord regeneration. The CS/ß-GP/HEC hydrogel and genetically transduced hADSCs using pseudo-lentiviruses-NGF were prepared. The mechanical properties, morphology and cytotoxicity of the hydrogel were investigated by rheometry, scanning electron microscope (SEM), and MTT assay, respectively. Rats animals were undergone spinal cord injury (SCI), then one-week post-injury, CS/ß-GP/HEC hydrogel, transduced hADSCs and transduced hADSCs/CS/ß-GP/HEC hydrogel injected into the site of the lesion. Animals with SCI and animals with laminectomy without SCI were considered as negative control and sham groups, respectively. Positive control group received no surgical intervention. At eight weeks post-injection, histological studies indicated a significant increase in cell proliferation, a smaller cavity in size at the SCI site as well as better locomotor functions for transduced hADSCs/CS/ß-GP/HEC hydrogel group (P ≤ 0.05) compared to other experimental groups. Our results showed that CS/ß-GP/HEC hydrogel in combination with transduced-hADSCs is able to successfully regenerate SCI. These results may be applicable in the selection of the best therapeutic strategy based on gene therapy and tissue engineering for SCI treatment.

Enrichment of cancer stem-like cells by the induction of epithelial-mesenchymal transition using lentiviral vector carrying E-cadherin shRNA in HT29 cell line.

A better understanding of cancer stem cells (CSCs) may facilitate the prevention and treatment of cancers. Epithelial-mesenchymal transition (EMT) is a process activated during invasion and metastasis of tumors. EMT induction in normal and tumor cells makes them more resistant to chemotherapy. E-cadherin is a membrane protein and plays a role in tumor invasion, metastasis, and prognosis. Downregulation of E-cadherin is a hallmark of EMT. Here, we created a model of cancer stem-like cells enrichment via EMT induction using E-cadherin downregulation in HT29 cell line using a lentiviral vector carrying shRNA. We aimed to evaluate cancer and anti-CSC chemotherapeutics screening. The markers of EMT and CSCs were assessed and compared with control cells using flow cytometry, real-time PCR, immunocytochemistry, western blot, migration assay, invasion assay, and colony formation assay. The transduced cells showed a mesenchymal morphology. High levels of EMT-related proteins were also expressed. These results confirmed that the transduced cells underwent EMT. In addition, we observed an increased population of E-cadherin-downregulated HT29 cell line among the cells expressing colon CSC markers (CD133+ and CD44+ ) after EMT induction. E-cadherin-downregulated cells were morphologically like mesenchymal cells, and the number of CD133+ - and CD44+ -cells (CSC-like cells) increased. These cells can be used as stable models to study cancer cells and screening of antitumor therapeutics.

Evaluation of the neuroprotective effects of electromagnetic fields and coenzyme Q10 on hippocampal injury in mouse.

Electromagnetic fields (EMFs) are reported to interfere with chemical reactions involving free radical production. Coenzyme Q10 (CoQ10) is a strong antioxidant with some neuroprotective activities. The purpose of this study was to examine and compare the neuroprotective effects of EMF and CoQ10 in a mouse model of hippocampal injury. Hippocampal injury was induced in mature female mice (25-30 g), using an intraperitoneal injection of trimethyltin hydroxide (TMT; 2.5 mg/kg). The experimental groups were exposed to EMF at a frequency of 50 Hz and intensity of 5.9 mT for 7 hr daily over 1 week or treated with CoQ10 (10 mg/kg) for 2 weeks following TMT injection. A Morris water maze apparatus was used to assess learning and spatial memory. Nissl staining and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) tests were also performed for the histopathological analysis of the hippocampus. Antiapoptotic genes were studied, using the Western blot technique. The water maze test showed memory improvement following treatment with CoQ10 and coadministration of CoQ10 + EMF. The Nissl staining and TUNEL tests indicated a decline in necrotic and apoptotic cell count following treatment with CoQ10 and coadministration of CoQ10 + EMF. The Western blot study indicated the upregulation of antiapoptotic genes in treatment with CoQ10, as well as coadministration. Also, treatment with EMF had no significant effects on reducing damage induced by TMT in the hippocampus. According to the results, EMF had no significant neuroprotective effects in comparison with CoQ10 on hippocampal injury in mice. Nevertheless, coadministration of EMF and CoQ10 could improve the neuroprotective effects of CoQ10.

Melatonin-pretreated adipose-derived mesenchymal stem cells efficeintly improved learning, memory, and cognition in an animal model of Alzheimer's disease.

Currently, mesenchymal stem cells (MSCs) based therapy has extensive attraction for Alzheimer's disease (AD). However, low survival rate of MSCs after transplantation is a huge challenging. The current study aimed to improve adipose-derived MSCs (AD-MSCs)-based therapy by their pre-treatment with melatonin (MT) 'a well-known antioxidant' in an animal model of AD. In this study, after isolating rat AD-MSCs from the epididymal white adipose tissues, the cells were pretreated with 5µM of MT for 24 hours. Forty male Wistar rats were randomly allocated to control, sham, amyloid-beta (Aß) peptide, AD-MSCs and MT-pretreated ADMSCs groups. The novel object recognition, passive avoidance test, Morris water maze and open field test were performed two months following the cell transplantation. The rats were sacrificed 69 days following cell therapy. The brain tissues were removed for histopathological analysis and also immunohistochemistry was performed for two Aß1-42 and Iba1 proteins. It has been revealed that both AD-MSCs and MT-AD-MSCs migrated to brain tissues after intravenous transplantation. However, MT-ADMSCs significantly improved learning, memory and cognition compared with AD-MSCs (P<0.05). Furthermore, clearance of Aß deposition and reduction of microglial cells were significantly increased in the MT-ADMSCs compared with AD-MSCs. Although stem cell therapy has been introduced as a promising strategy in neurodegenerative diseases, however, its therapeutic properties are limited. It is suggested that pretreatment of MSCs with melatonin partly would increase the cells efficiency and consequently could decrease AD complication including memory and cognition.

A review of accelerated wound healing approaches: biomaterial- assisted tissue remodeling.

Nowadays, due to a growing number of tissue injuries, in particular, skin wounds, induction and promotion of tissue healing responses can be considered as a crucial step towards a complete regeneration. Recently, biomaterial design has been oriented towards promoting a powerful, effective, and successful healing. Biomaterials with wound management abilities have been developed for different applications such as providing a native microenvironment and supportive matrices that induce the growth of tissue, creating physical obstacles against microbial contamination, and to be used as delivery systems for therapeutic reagents. Until now, numerous strategies aiming to accelerate the wound healing process have been utilized and studied with their own pros and cons. In this review, tissue remodeling phenomena, wound healing mechanisms, and their related factors will be discussed. In addition, different methods for induction and acceleration of healing via cell therapy, bioactive therapeutic delivery, and/or biomaterial-based approaches will be reviewed.

Enhancing pressure ulcer healing and tissue regeneration by using N-acetyl-cysteine loaded carboxymethyl cellulose/gelatin/sodium alginate hydrogel.

Prolonged pressure on the skin can result in pressure ulcers, which may lead to serious complications, such as infection and tissue damage. In this study, we evaluated the effect of a carboxymethyl cellulose/gelatin/sodium alginate (CMC/Gel/Alg) hydrogel containing N-acetyl-cysteine (NAC) on the healing of pressure ulcers. Pressure ulcers were induced by applying a magnet to the dorsum of rat skin. The wounds were then treated with sterile gauze, ChitoHeal Gel®, and CMC/Gel/Alg hydrogel dressings with or without NAC for the other groups. We evaluated the morphology, weight loss, swelling, rheology, blood compatibility, cytocompatibility, antioxidant capacity, and wound scratch of the prepared hydrogel. MTT assay revealed that the optimum concentration of NAC was 5 mg/ml, which induced higher cell proliferation and viability. Results of the histopathological evaluation showed increased wound closure, and complete re-epithelialization in the hydrogel-containing NAC group compared to the other groups. The CMC/Gel/Alg/5 mg/ml NAC hydrogel dressing showed 84% wound closure at 14 days after treatment. Immunohistochemical results showed a decrease in the level of TNF-α on day 14 compared day 7. Results of the qPCR assay revealed that NAC hydrogel increased the expression of Collagen type I and TGF-ß1 and decreased MMP2 and MMP9 mRNA on the 14th day. The results suggest that the CMC/Gel/Alg/5 mg/ml NAC hydrogel with antioxidant properties is an appropriate dressing for wound healing.

Decellularization and characterization of camel pericardium as a new scaffold for tissue engineering and regenerative medicine.

BACKGROUND: Valvular heart diseases (VHDs) have become prevalent in populations due to aging. Application of different biomaterials for cardiac valve regeneration and repair holds a great promise for treatment of VHD. Aortic valve replacement using tissue-engineered xenografts is a considered approach, and the pericardium of different species such as porcine and bovine has been studied over the last few years. It has been suggested that the animal origin can affect the outcomes of replacement. METHODS: So, herein, we at first decellularized and characterized the camel pericardium (dCP), then characterized dCP with H&E staining, in vitro and in vivo biocompatibility and mechanical tests and compared it with decellularized bovine pericardium (dBP), to describe the potency of dCP as a new xenograft and bio scaffold. RESULTS: The histological assays indicated less decluttering and extracellular matrix damage in dCP after decellularization compared to the dBP also dCP had higher Young Modulus (105.11), and yield stress (1.57 ± 0.45). We observed more blood vessels and also less inflammatory cells in the dCP sections after implantation. CONCLUSIONS: In conclusion, the results of this study showed that the dCP has good capabilities not only for use in VHD treatment but also for other applications in tissue engineering and regenerative medicine.

The Effect of Rosmarinic Acid on Neural Differentiation of Wartons Jelly-derived Mesenchymal Stem Cells in Two-dimensional and Three-dimensional Cultures using Chitosan-based Hydrogel.

Introduction: Numerous studies have shown the positive effects of rosmarinic acid on the nervous system. Rosmarinic acid as a herbal compound with anti-inflammatory effects can prevent thedestructive effect of inflammation on the nervous system. Furthermore, various studies haveemphasized the advantages of three-dimensional (3D) culture over the two-dimensional (2D) culture of cells. Methods: In this study, thermosensitive chitosan (CH)-based hydrogel as a 3D scaffoldwith the combination of chitosan, beta-glycerol phosphate and hydroxyl ethyl cellulose (CH-GP-HEC) loaded with rosmarinic acid was used to induce neuronal differentiation in humanWharton jelly stem cells. Also, cells were divided into eight groups to evaluate the effect of 3Dcell culture and to compare gene expression in different induction conditions. Results: The results ofgene expression analysis showed the highest expression of neuronal markers in Whartons jelly derived mesenchymal stem cells (WJMSCs) cultured in chitosan, beta-glycerol phosphate and hydroxyl ethyl cellulose (ch-gp-hec) loaded with differentiation medium androsmarinic acid. According to the results of gene expression, rosmarinic acid alone has a positiveeffect on the induction of expression of neural markers. This positive effect is enhanced by cellculture in 3D conditions. Conclusion: This study shows that rosmarinic acid can be considered an inexpensiveand available compound for use in neural tissue engineering. The results of this study indicatethat rosmarinic acid can be considered a cheap and available compound for use in neural tissueengineering.

The role of probiotics in tissue engineering and regenerative medicine.

Tissue engineering and regenerative medicine (TERM) as an emerging field is a multidisciplinary science and combines basic sciences such as biomaterials science, biology, genetics and medical sciences to achieve functional TERM-based products to regenerate or replace damaged or diseased tissues or organs. Probiotics are useful microorganisms which have multiple effective functions on human health. They have some immunomodulatory and biocompatibility effects and improve wound healing. In this article, we describe the latest findings on probiotics and their pro-healing properties on various body systems that are useable in regenerative medicine. Therefore, this review presents a new perspective on the therapeutic potential of probiotics for TERM.

Tissue engineering and regenerative medicine can design processes or products to restore, repair, or replace injured or diseased cells, tissues or organs. It contains the generation and making use of therapeutic stem cells, and engineered scaffolds for the manufacture of artificial organs. This field focuses on the development and application of new treatments to heal tissues and organs as well as repair functions lost due to damage, defects, disease or aging. The World Health Organization has described probiotics as "live microorganisms that, when administered in sufficient amounts, confer a health advantage on the host". Probiotics are found naturally in certain foods, such as kimchi and fermented yogurt. They are also found in your gut, where they partake in a type of important bodily processes, such as vitamin production, digestion, mood regulation, and immune function. Probiotics with their suitable pro-healing effects on different systems of the body can be used in regenerative medicine. Probiotic bacteria induce their beneficial effects via proven mechanisms including pathogens killing, modulating the gut microbiota, immunomodulatory effects, and anti-diabetic, anti-obesity and anti-cancer functions. Moreover, recent studies indicated that probiotics could neutralize infections caused by COVID-19. Probiotics are healthy microorganisms that exert multiple positive effects on human health, especially through the battle against pathogens and repairing different types of body tissues.

Computational design of a multi-epitope vaccine candidate against Langya henipavirus using surface proteins.

In July 2022, Langya henipavirus (LayV) was identified in febrile patients in China. There is currently no approved vaccine against this virus. Therefore, this research aimed to design a multi-epitope vaccine against LayV using reverse vaccinology. The best epitopes were selected from LayV's fusion protein (F) and glycoprotein (G), and a multi-epitope vaccine was designed using these epitopes, adjuvant, and appropriate linkers. The physicochemical properties, antigenicity, allergenicity, toxicity, and solubility of the vaccine were evaluated. The vaccine's secondary and 3D structures were predicted, and molecular docking and molecular dynamics (MD) simulations were used to assess the vaccine's interaction and stability with toll-like receptor 4 (TLR4). Immune simulation, codon optimization, and in silico cloning of the vaccine were also performed. The vaccine candidate showed good physicochemical properties, as well as being antigenic, non-allergenic, and non-toxic, with acceptable solubility. Molecular docking and MD simulation revealed that the vaccine and TLR4 have stable interactions. Furthermore, immunological simulation of the vaccine indicated its ability to elicit immune responses against LayV. The vaccine's increased expression was also ensured using codon optimization. This study's findings were encouraging, but in vitro and in vivo tests are needed to confirm the vaccine's protective effect.Communicated by Ramaswamy H. Sarma.

A comparative study of the effects of crab derived exosomes and doxorubicin in 2 & 3-dimensional in vivo models of breast cancer.

INTRODUCTION: Using tissue engineering and modifying the tumor microenvironment, three-dimensional (3D) in vitro and in vivo cancer modeling can be performed with appropriate similarity to native. Exosomes derived from different sources have recently been used in cancer studies due to their anticancer effects. In this study, the effect of crab derived exosomes in 2 & 3-dimensional (2& 3D) in vivo models of breast cancer (BC) were investigated and compared with the doxorubicin (DOX). METHODS: 2D and 3D models of BC were induced using the chitosan/ß-glycerol phosphate hydrogel (Ch/ß-GP) and 1 × 106 4T1 cells in the female mice aged 6-8 weeks. 1 mg/ml exosome and 5 mg/kg DOX were injected by intratumoral (IT), intravenous (IV), and intraperitoneal (IP) methods into mice on day 9, 13, and 17 with and without hydrogel as a drug delivery system. After 21 days, the mice were sacrificed, and the tissues (lung, liver, and tumor) were removed. The weight and size of the tumor were measured. Real-time PCR assessed changes of VEGF, Bcl2, and P53 genes expression levels. Nitric oxide (NO) secretion from the cancer 3D model was evaluated by Griess assay. RESULTS AND CONCLUSION: Based on the results, the size and weight of tumors in treated groups with exosomes and DOX were reduced significantly (P ≤ 0.001, P ≤ 0.002, P ≤ 0.02) in 2D and 3D models. Changes in VEGF, Bcl2 and P53 gene expression levels were less in the 3D model than in the 2D model. Drug delivery with hydrogel increased tumor inhibition compared to drug injection without hydrogel. Decreased NO secretion was observed in all treatment groups compared to the control group (untreated). Crab exosomes showed anti cancer effects on 2&3D models of BC. 3D model of BC showed greater drug resistance than the 2D model after treating with crab derived exosomes and DOX. 3D model of BC mimics native tumor better than 2D and can be used in cancer studies and for drug screening with greater confidence than 2D model. Also, the use of slow release drug delivery system reduced drug resistance in both models.

Development of meniscus cartilage using polycaprolactone and decellularized meniscus surface modified by gelatin, hyaluronic acid biomacromolecules: A rabbit model.

The lack of vascularization in the white-red and white zone of the meniscus causes these zones of tissue to have low self-healing capacity in case of injury and accelerate osteoarthritis (OA). In this study, we have developed hybrid constructs using polycaprolactone (PCL) and decellularized meniscus extracellular matrix (DMECM) surface modified by gelatin (G), hyaluronic acid (HU) and selenium (Se) nanoparticles (PCL/DMECM/G/HU/Se), following by the cross-linking of the bio-polymeric surface. Material characterization has been performed on the fabricated scaffold using scanning electron microscopy (SEM), Fourier transforms infrared (FTIR) spectroscopy, swelling and degradation analyses, and mechanical tests. In Vitro, investigations have been conducted by C28/I2 human chondrocyte culture into the scaffold and evaluated the cytotoxicity and cell/scaffold interaction. For the in vivo study, the scaffolds were transplanted into the defect sites of female New Zealand white rabbits. Good regeneration was observed after two months. We have concluded that the designed PCL/DMECM/G/HU construct can be a promising candidate as a meniscus tissue engineering scaffold to facilitate healing.

Toward in Vitro Production of Platelet from Induced Pluripotent Stem Cells.

Platelets (PLTs) are small anucleate blood cells that release from polyploidy megakaryocytes(MKs). PLT transfusion is standard therapy to prevent hemorrhage. PLT transfusion is donor-dependent way which have limitations including the inadequate donor blood supply, poor quality, and issues related to infection and immunity. Overcoming these obstacles is possible with in vitro production of human PLTs. Currently several cells have been considered as source to in vitro production of PLTs such as hematopoietic stem cells (HSCs), embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). However, HSCs are a limited source for PLT production and large-scale expansion of HSC-derived PLT remains difficult. Alternative sources can be ESCs which have unlimited expansion capacity. But ESCs have ethical issues related to destroying human embryos. iPSCs are considered as an ideal unlimited source for PLT production. They are able to differentiate into any cells and have the capacity of self-renewal. Moreover, iPSCs can be acquired from any donor and easily manipulated. Due to new advances in development of MK cell lines, bioreactors, feeder cell-free production and the ability of large scale generation, iPSC-based PLTs are moving toward clinical applicability and considering the minimal risk of alloimmunization and tumorigenesis of these products, there is great hopefulness they will become the standard source for blood transfusions in the future. This review will focus on how to progress of in vitro generation of PLT from stem cell especially iPSCs and some of the successful strategies that can be easily used in clinic will be described.

A Decrease in CD44 on Cell Surfaces (MKN-45 cell line) After RELA Knockout Using CRISPR/Cas9.

The NF-kB signaling pathway was introduced as a key pathway in carcinogenesis that is induced by inflammation in gastrointestinal malignancies. The RelA transcription factor is an important component of this signaling pathway. Furthermore, CD44 is implicated in the tumorigenesis and metastasis of gastric cancer. The aim of this study was to assay the effect of RELA knockout on CD44 expression in MKN45 cells. CRISPR/Cas9 was used to knock out RELA in MKN-45. The median fluorescence intensity (MFI) of CD44 before and after RELA knockout is analyzed in MKN45. The CRISPR/Cas9 vector pSpCas9 (BB)-2A-Puro (PX459) was used for gRNA cloning (two guides). The MKN-45 cell line was co-transfected. The purified co-transfected cells with puromycin were cultured and used for the RELA gene expression assay by real-time PCR. Flow cytometry was used for the analysis of the MFI of CD44+ in MKN45. The results showed that 180 nucleotide sequences between exon 2 and exon 3 of RELA were deleted in MKN45. RELA expression significantly (P<0.001) decreased after CRISPR/Cas9 knockout. Compared to the control group, the MFI of CD44 in transfected cells significantly decreased (P <0.001). Knockout of RELA significantly decreased CD44 expression in MKN45 cells. It can be concluded that the NF-kB signaling pathway via RELA is related to CD44 expression and consequently the tumorigenesis of gastric cancer. More studies about this relationship are recommended.

Tumor-resident adenosine-producing mesenchymal stem cells as a potential target for cancer treatment.

The development of new therapies based on tumor biology is one of the main topics in cancer treatment. In this regard, investigating the microenvironment and cellular composition of the tumor is of particular interest. Mesenchymal stem cells (MSCs) are a major group of cells in the tumor tissue and play a critical role in tumor growth and development. Investigating the mechanisms by which MSCs influence tumor growth and progression is very useful in establishing new therapeutic approaches. MSCs have some immunological capacities, including anti-inflammatory, immune-regulatory, and immune-suppressive abilities, which help the tumor growth in the inflammatory condition. They can suppress the proliferation and activation of CD4 + T cells and direct them toward the regulatory phenotype through the release of some factors such as indoleamine 2,3-dioxygenase, prostaglandin E2, and HO-1, PD-1 ligands (PD-L1 and PD-L2) and promote tolerance and apoptosis. Besides, these cells are able to produce adenosine. Adenosine has a key role in controlling the immune system by signaling through receptors located on the surface of immune cells. It plays a very essential role in tumor growth and progression. In the present review, we investigate and introduce adenosine-producing mesenchymal stem cells as a potential target for cancer treatment.