masoud soleimani

Most mortality in COVID-19 cases was due to the increased inflammatory cytokines and cytokine storm. As mesenchymal stem cells (MSCs) possess immunomodulatory properties, this study assessed the therapeutic effects of placental MSC-derived extracellular vesicles on the inflammation and pulmonary injury caused by COVID-19. 

The study was carried out in phases I (safety study, 101 patients) and II (efficacy study, 80 patients) in a randomized, double-blind study at four hospital centers from April 2021 to August 2021. In addition to standard treatments, 15 mL of normal saline solution containing 15×109 vesicles was injected intravenously for five consecutive days.

No reaction or adverse events were observed in any patients. In the intervention group, after 5 days of treatment, patients’ clinical status and oxygenation improved, and 75% of patients presented an increased SpO2 after 5 days. Besides, inflammatory parameters assessment indicated a 21% decrease in neutrophil-lymphocyte ratio and a 54% reduction in C-reactive protein after day five of the intervention. 

PMSC-derived extracellular vesicles were safe and well-tolerated, down-regulated cytokine storms, and restored oxygenation. Thus, they can be considered a promising therapeutic candidate for severe COVID-19.

Beta-thalassemia is a group of hereditary blood disorders caused by mutations in the β-globin gene cluster resulting in variable phenotypes ranging from severe anemia to clinically asymptomatic individuals. This study aimed to produce an in vitro model of β-thalassemia using CRISPR/Cas9 as an easily programmable, fast, more powerful, and efficient technique.

Guide RNA (gRNA)-Cas9 co-expression vectors were used for embryonic stem (ES) cell nucleofection. PCR, T7EI, and Hbb-b1 gene sequencing tests were done on extracted DNA to evaluate gene mutation. Following erythroid differentiation of ES cells, analysis of hemoglobin genes and erythroid transcription factors were assessed using a quantitative reverse transcription-polymerase chain reaction.

Sequencing data associated with clone 31 confirmed the deletion of 851 nucleotides between exon 2 and 3 in an Hbb-b1 allele in this clone and Indel mutation in exon 2 (-40bp/+38bp) from another allele of Hbb-b1. Significant expression of erythroid transcription factors was observed in wild type, Hbb-b1+/- and Hbb-b1-/- groups. The hbb-b1 gene expression in the Hbb-b1+/- group significantly decreased, although the Hbb-b1-/- group had zero expression.

Utilizing an efficient erythroid differentiation method on the CRISPR/Cas9-mediated Hbb-b1 knock-out in ES cells provides accessibility to the laboratory thalassemia model. This method could be used to produce a mouse model of β-thalassemia intermedia (Hbbth1/th1 mice), which are required for the identification of the molecular basis of β-thalassemia and enable testing of the therapeutic approaches such as the recovery of functional β or γ hemoglobin chain.

Wound healing is a major therapeutic concern in regenerative medicine. The current study aimed to investigate the second-degree burn wound treatment in rats using rat adipose- derived stem cells (ADSCs) and manganese nanoparticles (MnO2–NPs) in a polycaprolactone/gelatin electrospun nanofiber scaffold.

After the synthesis of nanoparticles and electrospinning of nanofibers, the SEM analysis, contact angle, mechanical strength, blood compatibility, porosity, swelling, biodegradability, cell viability, and adhesion assays were performed. According to the results, the PCL/Gel/5%MnO2-NPs nanofiber (Mn-5%) was determined to be the most suitable scaffold. The ADSCs-seeded Mn-5% scaffolds were applied as a burn wound dressing. The wound closure rate, IL-1β, and IL-6 level, hydroxyproline, and glycosaminoglycans content were measured, and the hematoxylin and eosin, Masson’s trichrome, and immunohistochemistry stainings were carried out.

Based on the results, in Mn+S (ADSCs+PCL/Gel/5%MnO2-NPs nanofiber) and N+S (ADSCs+PCL/Gel nanofiber) groups, the IL-6 and IL-1β levels were reduced, and the percentage of wound closure, glycosaminoglycans, and hydroxyproline content were increased compared to the control group (P<0.05). Also, the lowest amount of α-SMA was observed in these two groups, demonstrating stem cells' role in reducing α-SMA levels and thus preventing fibrosis. Moreover, the amount of α-SMA in the Mn+S group is lower than in the N+S group and, is closer to healthy skin. According to histology results, the best type of treatment was observed in the Mn+S group.

In conclusion, the ADSCs-seeded PCL/Gel/5%MnO2-NPs scaffold demonstrated considerable therapeutic effects in burn wound healing.

With the emergence of SARS CoV-2, we have witnessed numerous deaths and injuries. Due to the possibility of emergence of new strains, there is a need to improve treatment approaches. There are reports on the application of placenta-derived mesenchymal stem cells (p-MSCs) as a therapeutic approach. In this study, we investigated the therapeutic effects of these cells in patients with COVID-19.

Nine patients with severe and critical COVID-19 and severe inflammatory condition admitted to the ICU were candidates for cell therapy. For each subject, three 1 x 106 injections of p-MSC (cell/kg) were administered intravenously. The clinical manifestations of the patients and the occurrence of potential early complications as well as the levels of blood and inflammatory and anti-inflammatory parameters before and after cell therapy were investigated.

All treated patients tolerated the p-MSC injection and no acute side-effect was reported for the treatment. The PaO2/FiO2 level increased significantly in the patients after cell therapy. The analysis of the blood, inflammatory and anti-inflammatory parameters of the patients before and after cell therapy showed a significant decrease in the level of RBC and CRP, D-dimer, IL-6 and TNF-α and an increase in platelets and IL-10. The changes in WBC, lymphocytes, neutrophils, monocytes, Hb and PT and biochemical parameters in the serum, fibrinogen coagulation, PH, PCO2, Po2, HCO3 and O2 sat (%) were not statistically significant.

Based on the results, three intravenous injections of p-MSCs in severe and acute patients improved their inflammatory condition and clinical symptoms and had a significant effect on their inflammatory and blood parameters including RBC and platelet.

This study aimed to assess the potential of poly (acrylic acid)/tricalcium phosphate nanoparticles (PAA/triCaPNPs) scaffold in terms of biocompatibility and osteoconductivity properties the in-vivo evaluation as well as to investigate the performance of PAA/triCaPNPs scaffold (with or without exosomes derived from UC-MSCs) for bone regeneration of rat critical-sized defect.

PAA/triCaPNPs scaffold was made from acrylic acid (AA) monomer, N,N’-methylenebisacrylamide (MBAA), sodium bicarbonate (SBC), and ammonium persulfate (APS) through freeze-drying method. For in vivo evaluation, we randomly divided 24 rats into three groups. The rat calvarial bone defects were treated as follows: (1) Control group: defects without any treatment, (2) scaffold group: defects treated with scaffold only, (3) scaffold+exo group: defects treated with scaffold enriched with exosomes (1 μg/ μL, 150 μg per rat). Eight- and 12-weeks post-surgery, half of the animals were sacrificed and bone regeneration was examined through micro-computerized tomography (μ-CT), histological staining, and immunohistochemistry (IHC).

Quantitative analysis based on μ-CT scan images at 8 and 12 weeks post-implantation clearly indicated that healing rate for defects that were filled with scaffold enriched with exosome was significantly higher than defects filled with scaffold without exosome. The H&E and Masson staining results revealed that more new bone-like form developed in the scaffold+exo group than that in control and scaffold groups. Further, IHC staining for osteocalcin and CD31 confirmed that more bone healing in the scaffold+exo group at 12 weeks could be associated with osteogenesis and angiogenesis concurrently.

In the present study, we aimed to investigate the therapeutic potential of PAA/ triCaPNPs scaffold as a carrier of human UC-MSC-derived exosome to achieve the exosomecontrolled release on calvarial bone defect. The in vivo results indicated that the exosome-enriched scaffold could effectively minify the defect area and improve the bone healing in rat model, and as such it could be an option for exosome-based therapy.

Sulfur mustard (SM) or mustard gas is a blister chemical agent that causes pulmonary damage by triggering inflammation and oxidative injury. Alterations in microRNA (miR) transcript levels are found in pulmonary diseases and even inflammation. Therefore, we evaluated the expression levels of miR-20a-5p, miR-21-5p, and two target transcripts (transforming growth factor-beta [TGF-β1] and TGF-β receptor 2 [TGFR2]) in lung, serum, and skin samples from patients exposed to SM. Total RNA was extracted from lung, serum, and skin samples of patients with moderate (n=10) and high (n=10) SM exposure, as well as 10 healthy subjects. Following the synthesis of complementary deoxyribonucleic acid using real-time polymerase chain reaction, we determined the expression levels of miR-20a-5p, miR-21-5p, TGF-β1, and TGFR2 transcripts. Furthermore, we evaluated the sensitivity and specificity of the chosen miRs by employing receiver operating characteristic (ROC) curves and calculating the area under the ROC curve. The results showed that miR-20a-5p and miR-21-5p expressions in the groups with moderate and high SM exposure were significantly lower than the normal controls. The expression analysis demonstrated that TGFR2 was significantly less expressed in skin samples exposed to SM in both groups of patients compared with healthy controls. Furthermore, the TGF-β1 expression in the skin samples of the group with moderate SM exposure was lower than that of the normal control group. Our findings suggest that miR-20a-5p, miR-21-5p, TGF-β1, and TGFR2 expressions could be used as potential biomarkers for discriminating SM-exposed patients from healthy individuals.

This study focused on preparing a multiscale three-dimensional (3D) scaffold using tricalcium phosphate nanoparticles (triCaPNPs) in a substrate of poly(acrylic acid) (PAA) polymer for controlled release of exosomes in bone tissue engineering.

A scaffold was fabricated with a material mixture containing acrylic acid (AA) monomer, N,N’-methylenebisacrylamide (MBAA), ammonium persulfate (APS), sodium bicarbonate (SBC), and triCaPNPs called composite scaffold (PAA/triCaPNPs) via cross-linking and freezedrying methods. The synthesis process was easy and without complex multi-steps. Through mimicking the hybrid (organic-inorganic) structure of the bone matrix, we here chose triCaPNPs for incorporation into the PAA polymer. After assessing the physicochemical properties of the scaffold, the interaction of the scaffold with human umbilical cord mesenchymal stem cells (UCMSCs) such as attachment, proliferation, and differentiation to osteoblast cells was evaluated. In addition, we used DiI-labeled exosomes to verify the exosome entrapment and release from the scaffold.

The polymerization reaction of 3D scaffold was successful. Based on results of physicochemical properties, the presence of nanoparticles in the composite scaffold enhanced the mechanical stiffness, boosted the porosity with a larger pore size range, and offered better hydrophilicity, all of which would contribute to greater cell penetration, proliferation, and then better bone differentiation. In addition, our results indicated that our scaffold could take up and release exosomes, where the exosomes released from it could significantly enhance the osteogenic commitment of UC-MSCs.

The current research is the first study fabricating a multiscale scaffold using triCaPNPs in the substrate of PPA polymer using a cross-linker and freeze-drying process. This scaffold could mimic the nanoscale structure and chemical combination of native bone minerals. In addition, our results suggest that the PAA/triCaPNPs scaffold could be beneficial to achieve controlled exosome release for exosome-based therapy in bone tissue engineering.

Radiation therapy is one of the most important methods in treatment of cancer. Targeted metal nanoparticles (NPs) play an effective role in reducing ionizing radiation side effects through increasing the effect of ionizing radiation on cancer cells and controlling the harmful effect of radiation on healthy cells. The purpose of this study was to investigate the effect of targeted folic acid gold NPs (GNPs) using linker bovine serum albumin in the absorption and sensitivity of gold NPs in HeLa cervical cancer cells compared to non-targeted gold NPs.

In this study, GNPs were conjugated with folic acid by bovine serum albumin as the linker. The binding of bovine serum albumin and folic acid to GNPs was investigated by infrared (IR) spectroscopy. Toxicity was measured by the MTT method and based on the results, the GNPs’ non-toxic concentration was determined. The effect of targeted synthesized GNPs on their absorption and sensitivity were evaluated on HeLa cells.

The non-toxic concentration of GNPs was 12 μg/ml. Incubation of the cells with this concentration was performed for 2, 4, and 24 hours and it was observed that in 4 hours, the absorption rate of targeted GNPs was about 4 times higher than that of non-targeted GNPs. The radiosensitization ratios of targeted and non-targeted GNPs in the studied cancer cells relative to the control group (without NPs) exposed to 6 MV photon radiation were 1.32±0.02 and 1.19±0.02, respectively.

The use of bovine serum albumin linker to target GNPs has a significant effect on increasing the absorption of GNPs and the effect of ionizing radiation on HeLa cells under 6 MV photon beams.

Sulfur mustard or mustard gas is a blistering agent that has been used as a war weapon. Chemical veterans are people who have multiple injuries in different organs, especially in the skin. Studies have shown that the side effects of mustard gas are the result of alkylation with DNA, RNA, protein, and lipids, which leads to metabolic and genetic changes. The respiratory system and the skin are the main targets of mustard gas alkylation. microRNAs are small non-coding and single-stranded RNAs that play a role in the spatial and spatial regulation of protein synthesis and the stability of messenger RNA. The disruption of the expression of any miRNA gene will be equal to the disruption of the expression of several protein-coding genes, each of which can play an essential role in cell biology, so to investigate the changes in the expression of microRNA, miR-20a, in the skin of chemically injured people. In this study, 30 skin biopsy samples were collected, including 10 samples from patients with moderate SM, 10 samples from patients with severe SM, and 10 control samples. RNA extraction and cDNA synthesis were performed. The expression of the miR-20a gene was investigated using the Real-time PCR method. 5s rRNA gene was used as the internal control. GraphPad Prism 6.07 software was used for the statistical analysis of data. Roc curve was used to check the biomarker value of the miR-20a gene. In this study, according to the results of the Roc curve, the miR-20a gene in the skin has a biomarker value, but it needs more study.

Occasionally the disease severity of CML, nay progressat an accelerated rate and the blast phase could be associated with a worse prognosis and a higher mortality rate. Exosomes are nanosized lipid vesicles with the ability to regulate various intra and extracellular mechanisms through transferring their content including proteins, RNAs, miRNAs and DNAs to the tumor microenvironment.

In this study, we aimed to review exosomes structure and biogenesis as well as different exosome sources like CML cells, mesenchymal stromal cells (MSCs), and immune cells. Moreover, the effects of secreted exosomes on CML disease such as their impact on bone marrow niche, drug resistance, leukemic cells growth and CML disease progression is briefly described here.

Since exosomes play extensive roles in the regulation of niche altered by cancer, they can be very valuable in the clinic and in investigating the causes of resistance to treatment. Therefore, one of the therapeutic strategies that can be useful in the recovery process of this group of relapsed patients are exosomes.

In order to prevent disease advancement to accelerated and blast phases, further investigations and clinical trials are required to identify the exact function of exosomes. Therefore, exploring the content of these exosomes and optimizing their application for disease treatment, is needed to prevent disease progression and drug resistance.

This research intended to fabricate the thiolated chitosan-dextran nanoparticles (NPs) containing topotecan (TPH-CMD-TCS-NPs) to assess the ability of NPs in improving the efficacy of intravitreal chemotherapy of retinoblastoma in a rabbit xenograft model.

The coacervation process was used to produce the NPs. The cellular uptake of Cyanine-3 (CY3)-labeled NPs were investigated in human retinoblastoma Y79 cells using confocal microscopy. Also, the prepared TPH-CMD-TCS-NPs were tested in vitro by the tetrazolium dyes II (XTT) and flow cytometry in order to assess their cytotoxicity. In addition, a rabbit xenograft model of retinoblastoma was developed to test the antitumor effectiveness of TPH-CMD-TCS-NPs through intravitreal administration.

NPs had a mean diameter, polydispersity index, and zeta potential of 30 ± 4 nm, 0.24 ± 0.03 and +10 ± 3 mV, respectively. NPs (IC50s 40.40 compared to 126.20 nM, P = 0.022) were more effective than free topotecan as a dose-based feature. The tumor reaction to intravitreal chemotherapy with NPs was measured by evaluating the percentage of necrosis in the tumor tissue (91 ± 2%) and vitreous seeds (89 ± 9%) through hematoxylin and eosin (H&E) staining. In comparison with the control group, the TPHCMD-TCs-NPs treated group showed a significant decrease in tumor volume seven days after the intravitreal injection (P = 0.039). No significant changes were found in the ERG parameters after the intravitreal injection of TPH-CMD-TCs-NPs or TPH (P > 0.05).

This investigation revealed definitive antitumor efficacy of TPH-CMD-TCSNPs by intravitreal administration in the rabbit xenograft retinoblastoma model.

The occurrence of single and double-strand breaks of DNA damage is the major obstacle for proliferation under various environmental factors and, if not repaired, can result in many consequences, including mutation, cell death, and others. So, the present study was conducted to evaluate the damage of DNA and the expression status of DNA repair system genes before and after stem cell proliferation.

The MACS method isolated the umbilical cord blood hematopoietic stem cells (UCB-HSCs). In order to investigate cell death, the study of Annexin V/PI was done by flow cytometry. Comet assay made observation and identification of DNA breaks, and the expression of genes normally involved in the repair of DNA breaks was evaluated by real-time polymerase chain reaction.

The average number of stem cells increased by 1.9-fold after three days of proliferation. The apoptotic percentage of cells was negligible (less than 0.2%), and the purity of the CD34+ cells was reduced by about one-third in three days (67%). By examining the expression of DNA repair genes, including KU70, KU80, RAD51, and XRCC1, their increased fold change was not significant. In a microscopic examination of stem cells in the comet assay, there was no significant difference between DNA damage before (1.33% ± 0.31) and after (2.08% ± 0.92) replication.

In our investigation, neither DNA damage nor changes in the DNA break repair were observed. However, further studies are required to clarify the DNA break repair by recruiting more UCB-HSCs samples.

Beta-thalassemia is a group of inherited hematologic. The most HBB gene variant among Iranianbeta-thalassemia patients is related to two mutations of IVSII-1 (G>A) and IVSI-5 (G>C). Therefore, our aim ofthis study is to use the knock in capability of CRISPR Cas9 system to investigate the correction of IVSII-1 (G>A)variant in Iran. In this experimental study, following bioinformatics studies, the vector containingPuromycin resistant gene (PX459) was cloned individually by designed RNA-guided nucleases (gRNAs), andcloning was confirmed by sequencing. Proliferation of TLS-12 was done. Then, the transfect was set up by thevector with GFP marker (PX458). The PX459 vectors carrying the designed gRNAs together with Single-strandedoligodeoxynucleotides (ssODNs) as healthy DNA pattern were transfected into TLS-12 cells. After taking the singlecell clones, molecular evaluations were performed on single clones. Sanger sequencing was then performed toinvestigate homology directed repair (HDR). The sequencing results confirmed that all three gRNAs were successfully cloned into PX459 vector. In thetransfection phase, The TLS-12 containing PX459-gRNA/ssODN was selected. Molecular evaluations showed thatthe HBB gene was cleaved by the CRISPR/Cas9 system, that indicates that the performance of non-homologous endjoining (NHEJ) repair system. Sequencing in some clones cleaved by the T7E1 enzyme showed that HDR was notconfirmed in these clones. IVS-II-1 (G> A) mutation, which is the most common thalassemia mutation especially in Iran, the CRISPR/Cas9 system was able to specifically target the HBB gene sequence. This could even lead to a correction in themutation and efficiency of the HDR repair system in future research.

The most prevalent malignancy during childhood is B-cell acute lymphoblastic leukemia (B-ALL). Many genetic variations are the causes of B-ALL. IKZF1 alterations are prevalent in childhood B-ALL cases, which are associated with a poor prognosis. This studyexamined seventy-two pediatric B-ALL patients for the frequency of IKZF1 alteration and types of IKZF1 deletions.

In this study, bone marrow aspirate specimens at the stage of diagnosis in pediatric B–ALL patients were used. The diagnosis of B-ALL was performed following cytomorphology, cytochemistry, and immunophenotyping based on the 2016 World Health Organization (WHO) guidelines. ALL translocations, including TCF3-PBX1 fusion, ETV6-RUNX1 fusion, BCR-ABL1 fusion, and KMT2A-AFF1 fusion, were performed on DNA specimens of all patients. IKZF1 status was checked with the SALSA MLPA P335 ALL-IKZF1 probemix Kit.

The common-B ALL subtype was detected in 64/72 patients (88.9%). CD2 and CD13 aberrant expressions were found in 5/72 (6.9%) and 7/72 patients (9.7%), respectively. Molecular analysis for translocation revealed the frequency of ETV6-RUNX1 in 12/72 patients (16.7%) and BCR-ABL1 in 3/72 (4.2%). IKZF1 alterations were found in 13/72 patients (18%), of whom 10 (13.9%) had IKZF1 deletions. Three common types of IKZF1 deletions were found.

The frequency of IKZF1 deletion in this study is similar to the results already obtained in larger studies. The type of IKZF1 deletion related to poor outcomes has a higher frequency in this study. Because of the relatively high prevalence of IKZF1 deletion, its determination is important for better risk stratification and prognosis in pediatric B-ALL patients.

Microvesicles (MVs) are small membrane-bound particles that act as a vehicle to transfer their contents, such as proteins, RNAs, and miRNAs, to the target cells, making them undergo several changes. Depending on the origin and the target cell, MVs may cause cell survival or apoptosis. This study investigated the effects of MVs released from the leukemic K562 cell line on the human bone marrow mesenchymal stem cells (hBM-MSCs) to evaluate changes in the survival or apoptosis of the cells in an in vitro system.  

In this experimental study, we added the isolated MVs from the K562 cell line to hBM-MSCs, and after three and then seven days, subsequently cell count, cell viability, transmission electron microscopy, tracing MVs by carboxyfluorescein diacetate, succinimidyl ester (CFSE) solution, flow cytometry analysis for Annexin-V/PI staining and qPCR for the evaluation of BCL-2, KI67, and BAX expression were carried out. On the 10th day of the culture, hBM-MSCs were examined by Oil red O and Alizarin Red staining to evaluate their differentiation into adipocytes and osteoblasts.

There was a significant decrease in cell viability and KI67 and BCL-2 expression; however, BAX was significantly upregulated in the hBM-MSCs compared to control groups. Annexin-V/PI staining results also showed the apoptotic effects of K562-MVs on hBM-MSCs. Moreover, the differentiation of hBM-MSCs into adipocytes and osteoblasts was not observed. 

MVs from the leukemic cell line could affect the viability of normal hBM-MSCs and induce cell apoptosis.

MicroRNA is a form of non-coding RNAs that able to regulate gene expression. miR-424 is one of the members of the regulatory family, which plays an important role in the proliferation and differentiation of myeloid cells. Epigenetic changes can change the level of miR-424 under environmental factors. Therefore, the level of expression of miR-424 in U937 cells of the myeloid line was evaluated in this research under the influence of vitamin D3 (VitD3) and retinoic acid (RA).

In this study, U937 cells were cultured in the presence of VitD3, and RA to evaluate cell proliferation, viability via the trypan blue exclusion test, and expression level of miR-424 by real-time PCR at specific times.

Cell proliferation has shown a significant decrease in the RA group versus other groups during incubation times (P < 0.05). In VitD3 group, there was a significant increase in cell proliferation after 24- and 48-hours incubation periods versus other groups. In the VitD3 and RA groups, the increase of cell proliferation caused the downregulation of miR-424. In addition, the upregulation of VitD3 group and downregulation of the RA group were significant versus the control group (P < 0.05).

We concluded that the expression level of miR-424 was critically affected in the dose- and time-dependent of RA and VitD3 treatment in the U937 cell line. Treatment with VitD3 decreased the expression of miR-424 and RA treatment increase miR-424 expression level in physiological doses.

Angiogenesis is a characteristic of glioblastoma (GBM), the most fatal and therapeutic-resistant brain tumor. Highly expressed angiogenic cytokines and proliferated microvascular system made anti-angiogenesis treatments a thoroughly plausible approach for GBM treatment. Many trials have proved to be not only as a safe but also as an effective approach in GBM retardation in a certain time window as seen in radiographic response rates; however, they have failed to implement significant improvements in clinical manifestation whether alone or in combination with radio/chemotherapy. Bevasizumab, an anti-vascular endothelial growth factor-A (VEGF-A) antibody, is the only agent that exerts meaningful clinical influence by improving progression-free survival (PFS) and partially alleviate clinical symptoms, nevertheless, it could not prolong the overall survival (OS) in patients with GBM. The data generated from phase II trials clearly revealed a correlation between elevated reperfusion, subsequent to vascular normalization induction, and improved clinical outcomes which explicitly indicates anti-angiogenesis treatments are beneficial. In order to prolong these initial benefits observed in a certain period of time after anti-angiogenesis targeting, some aspects of the therapy should be tackled: recognition of other bypass angiogenesis pathways activated following antiangiogenesis therapy, identification of probable pathways that induce insensitivity to shortage of blood supply, and classifying the patients by mapping their GBM-related gene profile as biomarkers to predict their responsiveness to therapy. Herein, the molecular basis of brain vasculature development in normal and tumoral conditions is briefly discussed and it is explained how "vascular normalization" concept opened a window to a better comprehension of some adverse effects observed in anti-angiogenesis therapy in clinical condition. Then, the most targeted angiogenesis pathways focused on ligand/receptor interactions in GBM clinical trials are reviewed. Lastly, different targeting strategies applied in anti-angiogenesis treatment are discussed.

Mustard sulfur (SM) is a blister and has destructive effects on the lungs, eyes, and skin. MicroRNAs are non-coding RNA molecules that regulate many important cellular pathways. The clear association of microRNA expression changes in a wide range of diseases and their interception in various organs of the body, including the skin, has made them a suitable biomarker. This study aims at evaluating the changes in miR-21 gene expression in chemical warfare victims infected with SM. In this study, skin biopsy specimens including 10 veterans exposed to SM with moderate complications, 10 veterans exposed to SM with severe complications, and 10 control samples were collected, and then total RNA was extracted. cDNA synthesis was performed. MiR-21 gene expression was assessed using real-time PCR. 5 s rRNA gene was used as the internal control. Graph Pad Prism software version 6.07 was used for the statistical analysis of data. Roc curve was used to evaluate the biomarker value of the miR-21 gene. Increased expression of the miR-21 gene was observed in samples of SM veterans compared with normal samples. There was a statistically significant difference in the expression of the miR-21 gene in the skin samples of veterans exposed to SM with moderate complications and veterans exposed to SM with severe complications compared with the samples of control skin (P-value 0.0001). The expression of the miR-21 gene in the skin samples of veterans exposed to SM with severe complications and veterans exposed to SM with moderate complications in old age was not significantly related to the control sample (P-value = 0.8049, P-value = 0.3802). This study showed that the relative expression of miR-21 could be a potential biomarker in distinguishing SM veterans from healthy individuals but needs further researches..

Exosomes, as nano-sized extracellular vehicles acting as cell-to-cell communicators, are novel promising therapeutics in the area of bone tissue engineering. Moreover, magnetic nanoparticles, whose integration with other appropriate components is viewed as an intriguing approach to strengthen bone tissue engineering efficacy. We investigated the effect of magnetic enriched with exosomes on osteogenic differentiation.

Exosomes were isolated from human adipose-derived mesenchymal stem cells by Exo-spin™ kit (MSC-EX). Alginate (Alg) scaffold containing 1% (w/w) cobalt ferrite nanoparticles (CoFe2O4) was produced. MSC-EX were gently loaded onto Alg and Alg-cobalt ferrite (Alg-CF) scaffolds yielding Alg-EX and Alg-CF-EX scaffolds. The effects of MSC-Ex and magnetic hydrogel composite under an external static magnetic field (SMF) on proliferation and differentiation of MSCs were evaluated by alkaline phosphatase (ALP) activity measurement, alizarin red staining, and energy dispersive X-ray (EDX) analysis.

Our results showed that Alg and Alg-CF scaffolds were not only cytotoxic but also supported AdMSCs proliferation. MSC-EX loading of the scaffolds enhanced AdMSCs proliferation significantly. According to the results, Alg-CF-EX scaffolds under magnetic stimulation exhibited the most potent effect on osteogenic differentiation of cultured AdMSCs as evidenced by higher ALP activity and mineralization.

We provided evidence that the combination of Alg hydrogel, CFNPs, and MSC-EX resulted in the construction of a bone tissue-engineering scaffold that highly supports the osteogenic commitment of MSCs.

In apheresis, collecting an adequate number of CD34+ cells is required for successful autologous hematopoietic stem cell transplantation (auto-HSCT) procedure. It is difficult to harvest a sufficient number of stem cells in certain patients due to their old age and history of intensive chemotherapy. Plerixafor could mobilize stem cells and facilitate peripheral blood hematopoietic stem cell collection. However, not enough information is available on the appropriate time intervals from plerixafor administration to apheresis.

In this study, we aimed at evaluating the level of peripheral blood CD34+ cells at plerixafor administration time and every three hours to identify the peak time of circulating CD34+ cells.

Circulating CD34+ cells were enumerated by flow cytometry on day 4 post mobilization. Plerixafor was administered to patients with poor mobilization based on the count of peripheral blood hematopoietic stem cells. The number of circulating CD34+ cells was evaluated before and 3, 6, 9, and 12 hours after plerixafor administration to assess the time it takes for stem cells to reach their peak level.

The highest level of stem cell concentration was found in 9 hours after plerixafor administration with an increasing trend. A statistically significant relationship was also observed between factors including platelet count on the first day of GCSF injection and the day of stem cell infusion, leukocyte count on admission, and basal levels of CD34+ cells in peripheral blood and the amount of harvested stem cells.

We demonstrated that plerixafor causes an incremental trend in CD34+ cells mobilization, reaching its peak after 9 hours. Further research should be performed to provide insights into graft cells’ population and hematologic and immunological recovery

T cell immunoglobulin and mucin domain-3 (TIM-3) is an immune-checkpoint molecule that is upregulated following allogeneic immune responses and could play an important role in the development and pathogenesis of graft-versus-host disease (GVHD). The soluble form of TIM-3 (sTIM-3) is increased following the upregulation of membranous TIM-3.

The aim of this study was to evaluate the association between plasma level of sTIM-3 and acute GVHD (aGVHD) incidence in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT).

Blood samples were collected from 42 allo-HSCT patients and 20 healthy individuals 2 weeks after allo-HSCT. The plasma level of sTIM-3 was measured using enzyme-linked immunosorbent assay (ELISA). The clinical and demographic data of patients were collected from the clinical documents. Data analysis was evaluated using student t-test and one-way ANOVA tests. P-values less than 0.05 were assumed statistically significant.

Among 18 (42.8%) patients with aGVHD symptoms, 10 (23.8%) had severe GVHD and 8 (19%) experienced mild GVHD. Plasma sTIM-3 levels at day +14 were significantly higher in patients who developed aGVHD compared to allo-HSCT patients without GVHD and also the healthy control individuals (P-value = 0.015 and < 0.001). Among the aGVHD patients, the sTIM-3 levels in those with severe GVHD were approximately 2.5 times higher than those with mild GVHD (P-value < 0.001).

We have identified a high plasma level of sTIM-3 as a valuable biomarker in predicting the development of acute GVHD, especially severe aGVHD in allo-HSCT patients.

Graphene-based nanomaterials are being investigated for their biocompatibility and bioactivity, as well as their ability to improve osteogenic differentiation. In this research, the base material, reduced graphene oxide (rGO) sheets, were decorated with hydroxyapatite and strontium (rGO / HAp-Sr) to induce osteogenic differentiation in adipose-derived mesenchymal stem cells. Different techniques were used to determine the properties of the nanocomposite such as diffraction analysis techniques (XRD) and transmission electron microscopy (to evaluate the size and morphology of HAp-Sr on rGO plates), FT-IR (to analyze the nanocomposite functional group), Raman spectroscopy (to investigate possible disorders in nanocomposite structure and number of layers), induced dual plasma emission spectroscopy (to assess atomic concentration of Ca and Sr), zeta potential(electrical potential of the nanocomposite) and MTT (nanocomposite cytotoxicity assessment) were used. The ossification potential of the synthesized nanocomposite was investigated and confirmed using the calcium deposition test in dipose-derived mesenchymal stem cells. According to the obtained results, osteogenic differentiation induction is possible using synthesized nanocomposites without the need for chemical inducers.

Patients undergoing bone marrow transplantation (BMT) are high-risk during the Coronavirus disease 2019 (COVID-19) outbreak. Viral infections are a common complication in transplanted patients. Since BMT is a definitive line treatment for many hematological malignancies, the BMT unit should provide therapy services during the COVID-19 outbreak. According to studies over the past two years, following the COVID-19 prevention guidelines recommended by the World Health Organization (WHO) and European Group for Blood and Marrow Transplantation (EBMT) has made it possible to carry out this high-risk treatment. This review article presents the experiences and challenges of BMT centers during the outbreak of COVID-19.

The present study is a review article based on searching in medical-scientific databases, including PubMed, Scopus, MEDLINE, and Google Scholar, from 2020 to 2021. All articles were evaluated, and 30 articles were selected as the primary sources of study.

Regarding the stability and new strains emergence of coronavirus over the last two years, as well as the importance of BMT as the last-line treatment in some hematological malignancies, COVID-19 prevention is the first pivotal step for immunity of BMT donor and recipient. Training medical service personnel and patients will effectively prevent virus contagiousness and spread. Moreover, regular screening of medical staff can inhibit viral transmission to admitted patients. Stick to home quarantine in patients pre-and post-BMT restricts the risk of COVID-19 contamination.

Malignant middle cerebral artery infarct (mMCAI) largely contributes to high mortality and physical disability among adults. Surviving individuals may not have proper outcomes and suffer from severe lasting disabilities. Utilization of stem cells and paracrine factor for regenerative purposes is considered as a potential strategy for patients with neurological deficits. While preclinical stroke studies have shown that mesenchymal stem cells (MSCs) reduce post‑treatment neurological deficits and prevent disability and also promote recovery, few randomized clinical trials (RCT) have assessed exosome therapy in humans.

In this RCT, we assessed the safety of intraparenchymal injection placenta MSC‑derived Exosome in mMCAI patients with average age of 62 years between January, 2019, till September, 2020. The study was done in a single‑center as an open‑label RCT, with a 3‑months follow‑up. Primary outcomes assessed the safety and also disability indexes were followed.

Five mMCAI patients were included with mean NIHSS: 17.6 ± 5.02. The mean MRS was 3.25 ± 0.95 in three patients. No serious adverse events were observed. Hematoma or local reaction as excessive edema were not seen at the site of injection.

Intraparenchymal implantation of MSC‑EXO showed no post‑interventional adverse effects in five ischemic stroke patients. It is proposed Local injection Exosome treatment following mMCAI can be safe and in future, it would be applied as a supportive, restorative and preventive treatment in patients who suffer from acute ischemic stroke and post ischemic disability.