Cell Journal (Yakhteh)
Volume:25 Issue: 6, Jun 2023

Mesenchymal stromal cells (MSCs) play immunomodulatory role in various autoimmune diseases. Previouspre-clinical and clinical studies have shown that MSCs could be a therapeutic modality for psoriasis. However, themechanisms of treatment and its possible side effects are under investigation. In this study, the safety and probableefficacy of injecting allogeneic adipose-derived mesenchymal stromal cells (ADSCs) in psoriatic patients were evaluated. In this phase I clinical study with six months of follow-up, total number of 1×106 or 3×106cells/cm2 of ADSCs were injected into the subcutaneous tissue of each plaque as a single dose in three males and twofemales (3M/2F) with a mean age of 32.8 ± 8.18. The primary outcome was safety. Changes in clinical and histologicalindexes, the number of B and T lymphocytes in local and peripheral blood, and serum levels of inflammatory cytokineswere assessed. Paired t test was used to compare variables at two time points (baseline and six months after injection)and repeated measures ANOVA test was utilized for variables at three time points in follow-up visits. No major adverse effects such as burning, pain, itching, or any systemic side effects were observed followingADSCs injection, and the lesions showed slight to considerable improvement after injection. The mRNA expressionlevels of pro-inflammatory factors were reduced in the dermis of the patients after injection. The increased expressionlevel of Foxp3 transcription factor in the patient blood samples suggested modulation of inflammation after ADMSCsadministration. Six months after the intervention, no major side effects were reported, but skin thickness, erythema, andscaling of the plaques, as well as the PASI score, were decreased in majority of patients. Our study suggested that ADSC injection could be considered as a safe and effective therapeuticapproach for psoriatic plaques (registration number: IRCT20080728001031N24).

Efficient production of functional and mature alveolar epithelial is a major challenge for developing any cellreplacement therapy for lung degenerative diseases. The extracellular matrix (ECM) pro-vides a dynamic environmentand mediates cellular responses during development and maintenance of tissue functions. The decellularized ECM(dECM) which retains its native-like structure and bio-chemical composition can provide the induction of embryonicstem cell (ESC) differentiation toward the tissue-specific lineages during in vitro culture. Therefore, the aim of this studywas to evaluate the effect of sheep lung dECM-derived scaffold on differentiation and further maturation of ESC-derivedlung progenitor cells.

This study was an experimental study. In the first step, a sheep lung was decellularizedto achieve dECM scaffolds and hydrogels. Afterwards, the obtained dECM scaffold was evaluated for collagen andglycosaminoglycan contents, DNA quantification, and its ultrastructure. Next, the three experimental groups: i. Sheeplung dECM-derived scaffold, ii. Sheep lung dECM-derived hydrogel, and iii. Fibronectin-coated plates were comparedin their abilities to induce further differentiation of human embryonic stem cells (hESCs)-derived definitive endoderm(DE) into lung progenitor cells. The comparison was evaluated by immuno-staining and real-time polymerase chainreaction (PCR) assessments.

We found that the dECM-derived scaffold preserved its composition and native porous structures whilelacking nuclei and intact cells. All experimental groups displayed lung progenitor cell differen-tiation as revealed by theRNA and protein expression of NKX2.1, P63 and CK5. DE cells differenti-ated on dECM-derived scaffold and dECMderivedhydrogel showed significant upregulation of SOX9 gene expression, a marker of the distal airway epithelium.DE cells differentiated on the dECM-derived scaffold compared to the two other groups, showed enhanced expressionof SFTPC (type 2 alveolar epithelial [AT2] cell marker), FOXJ1 (ciliated cell marker), and MUC5A (secretory cell marker)genes.

Overall, our results suggest that dECM-derived scaffold improves the differentiation of DE cells towardslung alveolar progenitor cells in comparison with dECM-derived hydrogel and fibronectin-coated plates.

Neural stem cells (NSCs) are suitable therapeutic candidates. Here, we compare the proliferation rate,differentiation potential, and expression levels of specific markers in two groups of cultured NSCs derived from ratsubgranular (SGZ) and subventricular (SVZ) zones.

In this experimental study, NSCs isolated from SGZ and SVZ were cultured in α-minimalessential medium (α-MEM) supplemented with 1% penicillin/streptomycin, 10% fetal bovine serum (FBS), 20 ng/mlbasic fibroblast growth factor (bFGF), 20 ng/ml epidermal growth factor (EGF), and B27 supplement. Glial fibrillaryacidic protein (Gfap), p75 neurotrophin receptor (Ngfr), tyrosine kinase receptor A (TrkA), beta-tubulin III (βTIII), andNestin gene levels were compared via reverse transcription polymerase chain reaction (RT-PCR) in these NSCs.Nestin and Gfap protein levels were compared by immunoassay. Subsequently, both populations were induced with10-8 M selegiline for 48 hours, followed by immunohistochemical analysis of tyrosine hydroxylase (TH) levels. One-wayANOVA and Tukey’s post-test were used with a significance level of P<0.05.

Both groups were successfully expanded in vitro and expressed the neurotrophin receptor genes. The SGZNSCshad a significantly higher proliferation rate and significantly higher numbers of Nestin and Gfap-positive cells.Although the majority of selegiline-induced NSCs were TH-positive, we observed more TH-positive cells in SGZ-derivedNSCs and these SGZ-NSCs displayed a shorter differentiation time.

SGZ-derived NSCs appear to be a more appropriate candidate for therapeutic purposes based onproliferation rate, neurosphere size, and Gfap and Nestin expression levels, as well as differentiation time and THexpression level after dopaminergic induction.

Peroxiredoxin-3 (Prx-3) is widely acknowledged as an antioxidant that protects against mitochondrialreactive oxygen species. Nonetheless, its role in cardiac fibrosis has not been elucidated. We aim to explore the roleand mechanism of Prx-3 in cardiac fibrosis. In this experimental study, mice received subcutaneous injections of isoproterenol (ISO) for 14consecutive days (10 mg/kg/d for three days, followed by 5 mg/kg/d for 11 days) to establish a cardiac fibrosis model. Themice were subsequently injected with adenovirus-Prx-3 (ad-Prx-3) to enable Prx-3 overexpression. Echocardiographywas used to evaluate cardiac function. Mice heart fibroblasts were isolated and stimulated with transforming growthfactor β1 (TGFβ1) to induce fibrosis in vitro. Cells were also transfected with ad-Prx-3 for overexpression of Prx-3. Echocardiographic diameters and fibrosis markers indicated that Prx-3 could inhibit ISO-induced cardiacdysfunction and fibrosis. Fibroblasts with Prx-3 overexpression exhibited reduced activation, proliferation, and collagentranscription. We found that Prx-3 reduced the expression of NADPH oxidase 4 (NOX4) and reduced P38 levels. Aftertreatment with a P38 inhibitor, the Prx-3 overexpression-induced anti-fibrosis effect was mitigated. Prx-3 could protect against ISO-induced cardiac fibrosis by inhibiting the NOX4-P38 pathway.

The current study evaluated the expression profile and explored the therapeutic implications of Jagged 1in human thyroid cancer. This experimental study was conducted in 60 paired specimens of papillary thyroid andadjacent normal tissues. Gene expression was determined by quantitative real time polymerase chain reaction(qRT-PCR) and western blotting. Transfection of cancer cells was performed by using Lipofectamine 2000. The cellproliferation of PTC cells was estimated by MTT assay. Clonogenic assay was performed for analysis of colony formingpotential of cancer cells. The apoptosis of PTC cells was studied by using AO/EB and Annexin V-FITC/PI stainingmethods. Flow cytometry was done to analyze the cell cycle phase distribution of cancer cells. Migration and invasionPTC cells were determined respectively with the wound-healing and transwell assays. The impact of Jagged 1 silencingwas investigated in vivo in a xenografted mice model followed by Immunohistochemistry (IHC) analysis. We found significant (P<0.05) upregulation of Jagged 1 in human thyroid cancer. Silencing of Jagged 1 causedsignificant (P<0.05) reduction in proliferation and colony formation of MDA-T68 cells. The inhibitory effects of Jagged1 silencing were found to be due to the induction of apoptosis. We also found enhancement of Bax and repression ofBcl-2 protein levels in MDA-T68 cells. Wound healing assay indicated significant (P<0.05) inhibition of cell migration ofMDA-T68 thyroid cancer cells. Additionally, we found that invasion of the thyroid cancer cells was reduced by 55% uponsilencing of Jagged 1. Moreover, Jagged 1 silencing was found to cause inhibition of the Notch intracellular domain(NICD) and Notch target gene, Hes-1 expression. Finally, Jagged 1 silencing inhibited the xenografted tumors in vivo. The findings suggest that Jagged 1 regulates the development of thyroid cancer that may act as atherapeutic target for managing thyroid cancer.

Surgery and chemotherapy are the most common therapeutic strategies proposed for oral squamous cellcarcinoma (OSCC). However, some of the disadvantages associated with the current methods like unwanted sideeffects and poor drug response lead the scientist to seek for novel modalities and delivery approaches to enhance theefficacy of treatments. The study aimed to assess the effectiveness of disulfiram (DSF)-loaded Niosomes on cancerousphenotypes of the OSCC cells. In this experimental study, an optimum formulation of DSF-loaded Niosomes was developedfor the treatment of OSCC cells to reduce drug doses and improve the poor stability of DSF in the OSCC environment.The design expert software was utilized to optimize the particles in terms of size, polydispersity index (PDI), andentrapment effcacy (EE). Acidic pH increased the release rate of DSF from these formulations. The size, PDI, and EE of Niosomeswere more stable at 4°C compared to 25°C. The results indicated that DSF-loaded Niosomes could induce apoptosis(P=0.019) in the OSCC cells compared to the control group. Moreover, it could reduce colony formation ability(P=0.0046) and also migration capacity of OSCC cells (P=0.0015). Our findings indicated that the application of proper dose of DSF-loaded Niosomes (12.5 μg/ml) increasesapoptosis, decreases colony formation capacity and declines the migration ability of OSCC cells.

Psoriasis, an immune-mediated disorder, is a multifactorial disease of unidentified cause. This study aims to discover the possible biomarkers of this papulosquamous skin disease. The gene chip GSE55201, resulted from an experimental study, including 44 psoriasis patients and 30 healthy controls was downloaded from GEO and weighted gene co-expression network analysis was utilized to identify the hub genes. The key modules were determined using the module eigenvalues. We used biological functions, cellular components, and molecular functions in the Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes enrichment analysis in the gene metabolic pathway were used for enrichment analysis. Adjacency matrix was built by using power adjacency function and the power to turn the correlation to adjacency matrix was 4 with a topology fit index of 0.92. Using the weighted gene co-expression network analysis, 11 modules were identified. The green-yellow module eigenvalues were significantly associated with psoriasis (Pearson correlation=0.53, p<0.001). Candidate hub genes were determined by their higher connectivity and relationship with module eigenvalue. The genes including SIGLEC8, IL5RA, CCR3, RNASE2, CPA3, GATA2, c-KIT, and PRSS33 were recorded as the hub genes. In summary we can conclude that SIGLEC8, IL5RA, CCR3, RNASE2, CPA3, GATA2, c-KIT, and PRSS33 have an important role in the immune response regulation and could be considered as a potential diagnostic biomarker and therapeutic target for Psoriasis.

An association between microRNAs (miRNAs) and adhesion proteins expression with repeated implantationfailure (RIF) has been recently reported; however, these findings are controversial. This study aims to evaluatethe endometrial and circulating expressions of miR-145, miR-155-5p, and miR-224 in addition to the endometrialexpressions of membrane protein palmitoylated-5 (MPP-5) and endothelial cell adhesion molecule-1 (PECAM-1) inpatients with RIF compared to control subjects. This case-control study was carried out between June 2021-July 2022. Subjects included 17patients with RIF and 17 control subjects, who had previous spontaneous term pregnancy with a live birth, who referredto the Medical Centre of Arash Hospital, Tehran, Iran. Endometrial tissue samples were obtained via hysteroscopyand Pipelle catheter in the RIF and control subjects, respectively. Plasma samples were collected after ovulationin all subjects. The expression levels of MPP5, PECAM-1, miR-224, miR-145, and miR-155-5p were evaluated byquantitative real-time polymerase chain reaction (qRT-PCR). The student’s t test, chi-square, Mann-Whitney U, andanalysis of covariance (ANCOVA) were used for data analyses. RIF patients had less endometrial miR-155-5p expression, and higher endometrial and circulating expressions ofmiR-145 and miR-224 compared to control subjects. Endometrial PECAM-1 and MPP5 expression significantly decreased inpatients with RIF compared to the control group. There was a positive correlation between circulating miR-224 and endometrialmiR-155-5p, and between circulating miR-155-5p and endometrial PECAM-1 expression levels in patients with RIF. The present study suggests that circulating miR-224, endometrial miR-145, and PECAM-1 can bereliable, novel biomarkers for diagnosis of RIF.