Although recent progress in medicine has substantially reduced cardiovascular diseases (CVDs)-related mortalities, current
therapeutics have failed miserably to be beneficial for all patients with CVDs. A wide array of evidence suggests that
newly-introduced cell-free treatments (CFTs) have more reliable results in the improvement of cardiac function. The main
regeneration activity of CFTs protocols is based on bypassing cells and using paracrine factors. In this article, we aim to
compare various stem cell secretomes, a part of a CFTs strategy, to generalize their effective clinical outcomes for patients
with CVDs. Data for this review article were collected from 70 published articles (original, review, randomized clinical trials
(RCTs), and case reports/series studies done on human and animals) obtained from Cochrane, Science Direct, PubMed,
Scopus, Elsevier, and Google Scholar) from 2015 to April 2020 using six keywords. Full-text/full-length articles, abstract,
section of book, chapter, and conference papers in English language were included. Studies with irrelevant/insufficient/data,
or undefined practical methods were excluded. CFTs approaches involved in growth factors (GFs); gene-based therapies;
microRNAs (miRNAs); extracellular vesicles (EVs) [exosomes (EXs) and microvesicles (MVs)]; and conditioned media (CM).
EXs and CM have shown more remarkable results than stem cell therapy (SCT). GF-based therapies have useful results as
well as side effects like pathologic angiogenesis. Cell source, cell′s aging and CM affect secretomes. Genetic manipulation
of stem cells can change the secretome’s components. Growing progression to end stage heart failure (HF), propounds
CFTs as an advantageous method with practical and clinical values for replacement of injured myocardium, and induction
of neovascularization. To elucidate the secrets behind amplifying the expansion rate of cells, increasing life-expectancy, and
improving quality of life (QOL) for patients with ischemic heart diseases (IHDs), collaboration among cell biologist, basic
medical scientists, and cardiologists is highly recommended.
Objective: Extremely low-frequency magnetic field (ELF-MF) exposure, as a targeted tumor therapy, presents several
potential advantages. In this research, we investigated effects of different ELF-MF intensities on cell viability and
expression levels of the mammalian target of rapamycin (mTOR) and hsa_circ_100338 in the normal fibroblast (Hu02)
and human gastric adenocarcinoma (AGS) cell lines.
Materials and Methods: In this experimental study, cell lines of AGS and Hu02, were cultured under the exposure of ELFMF
with magnetic flux densities (MFDs) of 0.25, 0.5, 1 and 2 millitesla (mT) for 18 hours. The 3-(4, 5-dimethylthiazoyl-2-
yl)-2, 5-diphenyltetrazolium bromide (MTT) assay was used to evaluate the cell viability. Relative expression of mTOR
and hsa_circ_100338 RNAs was estimated by quantitative real-time polymerase chain reaction (qRT-PCR) technique.
Results: Viability of the normal cells was significantly increased at MFDs of 0.5, 1 and 2 mT, while viability of the
tumor cells was significantly decreased at MFD of 0.25 and increased at MFD of 2 mT. Expression level of mTOR was
significantly increased at the all applied MFDs in the normal cells, while it was significantly decreased at MFDs of 0.25
and 0.5mT in the tumor cells. MFDs of 1 and 2 mT in tumor cells inversely led to the increase in mTOR expression.
hsa_circ_100338 was downregulated in MFD of 0.25 mT and then it was increased parallel to the increase of MFD in
the normal and tumor cells.
Conclusion: Results of the present study indicated that ELF-MF at MFDs of 0.25 and 0.5 mT can lead to decrease
in the both mTOR and hsa_circ_100338 expression levels. Given the role of mTOR in cell growth, proliferation and
differentiation, in addition to the potential role of hsa_circ_100338 in metastasis, expression inhibition of these two
genes could be a therapeutic target in cancer treatment.
Objective: Tendon repair strategies usually are accompanied by pathological mineralization and scar tissue formation
that increases the risk of re-injuries. This study aimed to establish an efficient tendon regeneration method simultaneously
with a reduced risk of ectopic bone formation.
Materials and Methods: In this experimental study, tenogenic differentiation was induced through transforming
growth factor- β3 (TGFB3) treatment in combination with the inhibiting concentrations of bone morphogenetic proteins
(BMP) antagonists, gremlin-2 (GREM2), and a Wnt inhibitor, namely sclerostin (SOST). The procedure’s efficacy was
evaluated using real-time polymerase chain reaction (qPCR) for expression analysis of tenogenic markers and osteochondrogenic
marker genes. The expression level of two tenogenic markers, SCX and MKX, was also evaluated by
immunocytochemistry. Sirius Red staining was performed to examine the amounts of collagen fibers. Moreover, to
investigate the impact of the substrate on tenogenic differentiation, the nanofibrous scaffolds that highly resemble
tendon extracellular matrix was employed.
Results: Aggregated features formed in spontaneous normal culture conditions followed by up-regulation of tenogenic
and osteogenic marker genes, including SCX, MKX, COL1A1, RUNX2, and CTNNB1. TGFB3 treatment exaggerated
morphological changes and markedly amplified tenogenic differentiation in a shorter period of time. Along with TGFB3
treatment, inhibition of BMPs by GREM2 and SOST delayed migratory events to some extent and dramatically reduced
osteo-chondrogenic markers synergistically. Nanofibrous scaffolds increased tenogenic markers while declining the
expression of osteo-chondrogenic genes.
Conclusion: These findings revealed an appropriate in vitro potential of spontaneous tenogenic differentiation of eq-
ASCs that can be improved by simultaneous activation of TGFB and inhibition of osteoinductive signaling pathways.
Objective: The main objective of this study is to determine the myogenic effects of skeletal muscle extracellular matrix,
vascular endothelial growth factor and human umbilical vein endothelial cells on adipose-derived stem cells to achieve
a 3-dimensional engineered vascular-muscle structure.
Materials and Methods: The present experimental research was designed based on two main groups, i.e. monoculture
of adipose tissue-derived stem cells (ADSCs) and co-culture of ADSCs and human umbilical vein endothelial cells
(HUVECs) in a ratio of 1:1. Skeletal muscle tissue was isolated, decellularized and its surface was electrospun using
polycaprolactone/gelatin parallel nanofibers and then matrix topography was evaluated through H&E, trichrome
staining and SEM. The expression of MyHC2 gene and tropomyosin protein were examined through real-time reverse
transcription polymerase chain reaction (RT-PCR) and immunofluorescence, respectively. Finally, the morphology
of mesenchymal and endothelial cells and their relationship with each other and with the engineered scaffold were
examined by scanning electron microscopy (SEM).
Results: According to H&E and Masson’s Trichrome staining, muscle tissue was completely decellularized.
SEM showed parallel Polycaprolactone (PCL)/gelatin nanofibers with an average diameter of about 300 nm. The
immunofluorescence proved that tropomyosin was positive in the ADSCs monoculture and the ADSCs/HUVECs coculture
in horse serum (HS) and HS/VEGF groups. There was a significant difference in the expression of the MyHC2
gene between the ADSCs and ADSCs/HUVECs culture groups (P<0.05) and between the 2D and 3D models in HS/
VEGF differentiation groups (P<001). Moreover, a significant increase existed between the HS/VEGF group and other
groups in terms of endothelial cells growth and proliferation as well as their relationship with differentiated myoblasts
Conclusion: Co-culture of ADSCs/HUVECs on the engineered cell-free muscle scaffold and the dual effects of VEGF
can lead to formation of a favorable engineered vascular-muscular tissue. These engineered structures can be used as
an acceptable tool for tissue implantation in muscle injuries and regeneration, especially in challenging injuries such as
volumetric muscle loss, which also require vascular repair.
Objective: In this study, we aimed to develop new Lipo-niosomes based nanoparticles loaded with Amphotericin B
(AmB) and Thymus Essential Oil (TEO) and test their effectiveness in the treatment of fungal-infected human adipose
stem cells (hASCs).
Materials and Methods: In this experimental study, optimal formulation of AmB and TEO loaded lipo-niosome (based
on lipid-surfactant thin-film hydration method) was chemically, and biologically characterized. Therefore, encapsulation
capacity, drug release, size, and the survival rate of cells with different concentrations of free and encapsulated AmB/
TEO were evaluated using the MTT method, and its antifungal activity was compared with conventional AmB.
Results: Lipo-Niosome containing Tween 60 surfactant: cholesterol: Dipalmitoyl phosphatidylcholine (DPPC):
Polyethylene glycol (PEG) with a ratio of 20:40:60:3 were chosen as optimal formulation. Lipo-Niosomes entrapment
efficiency was 94.15%. The drug release rate after 24 hours was 52%, 54%, and 48% for Lipo-AmB, Lipo-TEO, and
Lipo-AmB/TEO, respectively. Physical and chemical characteristics of the Lipo-Niosomes particles indicated size
of 200 nm and a dispersion index of 0.32 with a Zeta potential of -24.56 mv. Furthermore, no chemical interaction
between drugs and nano-carriers was observed. The cell viability of adipose mesenchymal stem cells exposed to 50
μg/ml of free AmB, free TEO, and free AmB/TEO was 13.4, 58, and 36.9%, respectively. Whereas the toxicity of the
encapsulated formulas of these drugs was 48.9, 70.8, and 58.3% respectively. The toxicity of nanoparticles was very
low (8.5%) at this concentration. Fluorescence microscopic images showed that the antifungal activity of Lipo-AmB/
TEO was significantly higher than free formulas of AmB, TEO, and AmB/TEO.
Conclusion: In this study, we investigated the efficacy of the TEO/AmB combination, in both free and encapsulatedniosomal
form, on the growth of fungal infected-hASCs. The results showed that the AmB/TEO-loaded Lipo-Niosomes
can be suggested as a new efficient anti-fungal nano-system for patients treated with hASCs.
Objective: Multiple sclerosis (MS) is a complex multifactorial neuro-inflammatory disorder. This complexity arises from
the evidence suggesting that MS is developed by interacting with environmental and genetic factors. This study aimed
to evaluate the miR-106a, miR-125b, and miR330- expression levels in relapsing-remitting multiple sclerosis (RRMS)
patients. The miRNAs' impact on TNFSF4 and Sp1 genes through the NF-кB/TNF-α signaling pathway was analyzed
by measuring the expression levels in case and controls.
Materials and Methods: In this in silico-experimental study, we evaluated the association of miR-106a, miR-
125b, and miR330- with TNFSF4 and SP1 gene expression levels in 60 RRMS patients and 30 healthy controls by
real-time polymerase chain reaction (PCR).
Results: The expression levels of miR-330, miR-106a, and miR125-b in blood samples of RRMS patients were
predominantly reduced. The expression of TNFSF4 in patients demonstrated a significant enhancement, in contrast to
the diminishing Sp1 gene expression level in controls.
Conclusion: Our ﬁndings indicated an association between miR-106a and miR-330 and miR125-b expression
and RRMS in our study population. Our data suggested that the miR106-a, miR125-b, and mir330- expression are
correlated with TNFSF4 and Sp1 gene expression levels.
Objective: Transforming growth factor-beta (TGF-β) superfamily and its members that include bone morphogenetic
protein 15 (BMP15), anti-Mullerian hormone (AMH), growth /differentiation factor-9 (GDF9), and their respective
receptors: BMPR1A, BMPR1B, and BMPR2 have been implicated as key regulators in various aspects of ovarian
function. The abnormal function of the ovaries is one of the main contributing factors to polycystic ovarian syndrome
(PCOS), so this study aimed to investigate the mRNA expression proﬁle of these factors in granulosa (GCs) and
cumulus cells (CCs) of those patients.
Materials and Methods: The case-control research was conducted on 30 women (15 infertile PCOS and 15
normo-ovulatory patients, 22≤age ≤38 years old) who underwent ovarian stimulation for in vitro fertilization (IVF)/
intracytoplasmic sperm injection (ICSI) cycle. GCs/CCs were obtained during ovarian puncture. The expression
analysis of the aforementioned genes was quantified using real-time polymerase chain reaction (PCR).
Results: AMH and BMPR1A expression levels were significantly increased in GCs of PCOS compared to the control group.
In contrast, GDF9, BMP15, BMPR1B, and BMPR2 expressions were decreased. PCOS' CC showed the same expression
patterns. GDF9 and AMH were effectively expressed in normal CCs, and BMP15 and BMPR1B in normal GCs (P<0.05).
Conclusion: Differential gene expression levels of AMH and its regulatory factors and their primary receptors were
detected in granulosa and cumulus cells in PCOS women. Since the same antagonist protocol for ovarian stimulation
was used in both PCOS and control groups, the results were independent of the protocols. This diversity in gene
expression pattern may contribute to downstream pathways alteration of these genes, which are involved in oocyte
competence and maturation.
Objective: The main goal was to evaluate the effects of alginate on human sperm parameters during cryopreservation.
Materials and Methods: In this prospective study, twenty-five normozoospermic samples were divided into two groups,
encapsulated with 1% alginate and the control group. The samples were then frozen by rapid freezing. Different sperm
parameters including motility, normal morphology, viability, acrosome reaction, and DNA integrity, were examined
before freezing and after thawing.
Results: All sperm parameters had a significant decrease after thawing compared to before freezing. Our data
showed a significant decrease in sperm motility of the alginate group but sperm viability, normal morphology, and
DNA fragmentation were similar between the two groups. However, the rates of intact acrosome and native DNA were
significantly lower in the control group compared to the alginate group (45.12 ± 11.1 vs. 55.25 ± 10.69 and 52.2 ± 11.92
vs. 68.12 ± 10.15, respectively, P<0.05).
Conclusion: It seems that alginate
There are a lot of data about the correlation of SARS-CoV-2 infection and hypertension (HTN), but most of them
are in the increased risk of morbidity and mortality in patients with HTN. SARS-CoV-2 can interfere with host cells
through the renin-angiotensin system (RAS) via the angiotensin-converting enzyme 2 (ACE2) receptor. RAS activation
is associated with pro-inflammatory effects through the ACE/Ang II/ Angiotensin II type 1 receptor (AT1R) pathway
or anti-inflammatory effects through ACE2/Ang1-7/Mas axis. In the current paper, we discuss the pathophysiology of
newly diagnosed HTN and its effect on morbidity in patients with coronavirus disease 2019 (COVID-19).