Long non-coding RNA (lncRNA) H19 has essential roles in growth, migration, invasion, and metastasis of
most cancers. H19 dysregulation is present in a large number of solid tumors and leukemia. However, the expression
level of H19 in acute lymphoblastic leukemia (ALL) has not been elucidated yet. The current study aimed to explore
H19 expression in ALL patients and cell lines.
Materials and Methods:
This experimental study was conducted in bone marrow (BM) samples collected from 25
patients with newly diagnosed ALL. In addition, we cultured the RPMI-8402, Jurkat, Ramos, and Daudi cell lines
and assessed the effects of internal (hypoxia) and external (chemotherapy medications L-asparaginase [ASP] and
vincristine [VCR]) factors on h19 expression. The expressions of H19, P53, c-Myc, HIF-1α and β-actin were performed
using quantitative real-time polymerase chain reaction (qRT-PCR) method.
There was significantly increased H19 expression in the B-cell ALL (B-ALL, P<0.05), T-cell ALL (T-ALL,
P<0.01) patients and the cell lines. This upregulation was governed by the P53, HIF-1α, and c-Myc transcription
factors. We observed that increased c-Myc expression induced H19 expression; however, P53 adversely affected H19
expression. In addition, the results indicated that chemotherapy changed the gene expression pattern. There was a
considerable decrease in H19 expression after exposure to chemotherapy medications; nonetheless, hypoxia induced
H19 expression through P53 downregulation.
Our findings suggest that H19 may have an important role in pathogenesis in ALL and may act as a
promising and potential therapeutic target.
Exercise can attenuate mitochondrial dysfunction caused by aging. Our study aimed to compare 12
weeks of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) on the expression
of mitochondria proteins [e.g., AMP-activated protein kinase (AMPK), Estrogen-related receptor alpha (ERRα), p38
mitogen-activated protein kinase (P38MAPK), and Peroxisome proliferator-activated receptor gamma coactivator
1-alpha (PGC1-α)] in gastrocnemius muscle of old female rats.
Materials and Methods:
In this experimental study, thirty six old female Wistar rats (18-month-old and 270-310 g) were
divided into three groups: i. HIIT, ii. MICT, and iii. Control group (C). The HIIT protocol was performed for 12 weeks with
16-28 minutes (2 minutes training with 85-90% VO2max in high intensity and 2 minutes training with 45-75% VO2max low intensity). The MICT was performed for 30-60 minutes with the intensity of 65-70% VO2max. The gastrocnemius muscle expression of AMPK, ERRα, P38MAPK, and PGC1α proteins were determined by Western blotting.
The expression of AMPK (P=0.004), P38MAPK (P=0.003), PGC-1α (P=0.028), and ERRα (P=0.006) in HIIT
was higher than C group. AMPK (P=0.03), P38MAPK (P=0.032), PGC-1α (P=0.015), and ERRα (P=0.028) in MICT
was higher than the C group. Also expression of AMPK (P=0.008), P38MAPK (P=0.009), PGC-1α (P=0.020) and ERRα
(P=0.014) in MICT was higher than MICT group.
It seems that exercise training has beneficial effects on mitochondrial biogenesis, but the HIIT training
method is more effective than MICT in improving mitochondrial function in aging.
Although the role of obesity and diabetes mellitus (DM) in male infertility is well established, little information
about the underlying cellular mechanisms in infertility is available. In this sense, nuclear factor kappa-B (NF-kB) has
been recognized as an important regulator in obesity and DM; However, its function in the pathogenesis of male
infertility has never been studied in obese or men who suffer from diabetes. Therefore, the main goal of current research
is assessing NF-kB existence and activity in ejaculated human spermatozoa considering the obesity and diabetics
condition of males.
Materials and Methods:
In an experimental study, the ELISA technique was applied to analyze NF-kB levels in sperm
of four experimental groups: non-obese none-diabetic men (body mass index (BMI) <25 kg/m2; control group; n=30),
obese non-diabetic men (BMI >30 kg/m2; OB group; n=30), non-obese diabetic men (BMI <25 kg/m2; DM group; n=30),
and obese diabetic men (BMI >30 kg/m2; OB-DM group; n=30) who were presented to Royan Institute Infertility Center.
In addition, protein localization was shown by Immunocytofluorescent assay. Sperm features were also evaluated using
The diabetic men were older than non-diabetic men regardless of obesity status (P=0.0002). Sperm progressive
motility was affected by obesity (P=0.035) and type A sperm progressive motility was affected by DM (P=0.034). The
concentration of sperm (P=0.013), motility (P=0.025) and morphology (P<0.0001) were altered by obesity × diabetes
interaction effects. The NF-kB activity was negatively influenced by the main impact of diabetics (P=0.019). Obesity
did not affect (P=0.248) NF-kB activity. Uniquely, NF-kB localized to the midpiece of sperm and post-acrosomal areas.
The current study indicated a lower concentration of NF-kB in diabetic men, no effect of obesity on NF-kB
was observed yet. Additionally, we revealed the main obesity and diabetes effects, and their interaction effect adversely
influenced sperm characteristics.
Decellularized uterine scaffold, as a new achievement in tissue engineering, enables recellularization and
regeneration of uterine tissues and supports pregnancy in a fashion comparable to the intact uterus. The acellular
methods are methods preferred in many respects due to their similarity to normal tissue, so it is necessary to try to
introduce an acellularization protocol with minimum disadvantages and maximum advantages. Therefore, this study
aimed to compare different protocols to achieve the optimal uterus decellularization method for future in vitro and in
vivo bioengineering experiments.
Materials and Methods:
In this experimental study, rat uteri were decellularized by four different protocols (P) using
sodium dodecyl sulfate (SDS), with different doses and time incubations (P1 and P2), SDS/Triton-X100 sequentially
(P3), and a combination of physical (freeze/thaw) and chemical reagents (SDS/Triton X-100). The scaffolds were
examined by histopathological staining, DNA quantification, MTT assay, blood compatibility assay, FESEM, and
Histology assessment showed that only in P4, cell residues were completely removed. Masson’s trichrome
staining demonstrated that in P3, collagen fibers were decreased; however, no damage was observed in the collagen
bundles using other protocols. In indirect MTT assays, cell viabilities achieved by all used protocols were significantly
higher than the native samples. The percentage of red blood cell (RBC) hemolysis in the presence of prepared scaffolds
from all 4 protocols was less than 2%. The mechanical properties of none of the obtained scaffolds were significantly
different from the native sample except for P3.
Uteri decellularized with a combination of physical and chemical treatments (P4) was the most favorable
treatment in our study with the complete removal of cell residue, preservation of the three-dimensional structure,
complete removal of detergents, and preservation of the mechanical property of the scaffolds.
Organ transplantation is the last therapeutic choice for end-stage liver failure, which is limited by the lack of
sufficient donors. Decellularized liver can be used as a suitable matrix for liver tissue engineering with clinical application
potential. Optimizing the decellularization procedure would obtain a biological matrix with completely removed cellular
components and preserved 3-dimensional structure. This study aimed to evaluate the decellularization efficacy through
three anatomical routes.
Materials and Methods:
In this experimental study, rat liver decellularization was performed through biliary duct (BD),
portal vein (PV), and hepatic vein (HV); using chemical detergents and enzymes. The decellularization efficacy was
evaluated by measurement of DNA content, extracellular matrix (ECM) total proteins, and glycosaminoglycans (GAGs).
ECM preservation was examined by histological and immunohistochemical (IHC) staining and scanning electron
microscopy (SEM). Scaffold biocompatibility was tested by the MTT assay for HepG2 and HUVEC cell lines.
Decellularization through HV and PV resulted in a transparent scaffold by complete cell removal, while the BD
route produced an opaque scaffold with incomplete decellularization. H&E staining confirmed these results. Maximum
DNA loss was obtained using 1% and 0.5% sodium dodecyl sulfate (SDS) in the PV and HV groups and the DNA
content decreased faster in the HV group. At the final stages, the proteins excreted in the HV and PV groups were
significantly less than the BD group. The GAGs level was diminished after decellularization, especially in the PV and
HV groups. In the HV and PV groups the collagen amount was significantly more than the BD group. The IHC and SEM
images showed that the ECM structure was preserved and cellular components were entirely removed. MTT assay
showed the biocompatibility of the decellularized scaffold.
The results revealed that the HV is a more suitable route for liver decellularization than the PV and BD.
Preeclampsia (PE) is a pregnancy related disorder with prevalence of 6-7%. Insufficient trophoblastic
invasion leads to incomplete remodeling of spiral arteries and consequent decrease in feto-placental perfusion. Altered
placental expression of tissue inhibitors of matrix metalloproteinase (TIMPs) is considered to be involved in this process
while the balance between matrix metalloproteinases (MMPs) and TIMPs contributes to remodeling of the placenta
and uterine arteries by degradation and refurbishing of extracellular matrix (ECM). Therefore, TIMPs, fetal expression
pattern was evaluated with the aim of its potential to be used as a determinant for the (early) detection of PE.
Materials and Methods:
In this case-control study, cell free fetal RNA (cffRNA) released by placenta into the maternal
blood was used to determine expression patterns of TIMP1, 2, 3 and 4 in the severe preeclamptic women in comparison
with the normal pregnant women. Whole blood from 20 preeclamptic and 20 normal pregnant women in their 28-32
weeks of gestational age was collected. The second control group consisted of 20 normal pregnant women in either 14
or 28 weeks of gestation (each 10). cffRNA was extracted from plasma and real-time polymerase chain reaction (PCR)
was done to determine the expression levels of TIMP1, 2, 3 and 4 genes.
Statistical analysis of the results showed significant higher expression of TIMP1-4 in the preeclamptic women
in comparison with the control group (P=0.029, 0.037, 0.037 and 0.049, respectively). Also, an increased level of TIMPs
expression was observed by comparing 14 to 28 weeks of gestational age in the normal pregnant women in the second
An increased cffRNA expression level of TIMPs may be correlated with the intensity of placental vascular
defect and may be used as a determinant of complicated pregnancies with severe preeclampsia.
The multimodality treatment of cancer provides a secure and effective approach to improve the outcome
of treatments. Cold atmospheric plasma (CAP) has got attention because of selectively target and kills cancer cells.
Likewise, gold nanoparticles (GNP) have been introduced as a radiosensitizer and drug delivery with high efficacy and
low toxicity in cancer treatment. Conjugating GNP with indocyanine green (ICG) can develop a multifunctional drug
to enhance radio and photosensitivity. The purpose of this study is to evaluate the anticancer effects of GNP@ICG in
radiotherapy (RT) and CAP on DFW melanoma cancer and HFF fibroblast normal cell lines.
Materials and Methods:
In this experimental study, the cells were irradiated to RT and CAP, alone and in combination
with or without GNP@ICG at various time sequences between RT and CAP. Apoptosis Annexin V/PI, MTT, and colony
formation assays evaluated the therapeutic effect. Finally, the index of synergism was calculated to compare the results.
Results: Most crucially, the cell viability assay showed that RT was less toxic to tumors and normal cells, but CAP
showed a significant anti-tumor effect on melanoma cells with selective toxicity. In addition, cold plasma sensitized
melanoma cells to radiotherapy so increasing treatment efficiency. This effect is enhanced with GNP@ICG. In
comparison to RT alone, the data showed that combination treatment greatly decreased monolayer cell colonization
and boosted apoptotic induction.
The results provide new insights into the development of better approaches in radiotherapy of melanoma
cells assisted plasma and nanomedicine.
Despite of antiviral drugs and successful treatment, an effective vaccine against hepatitis C virus (HCV)
infection is still required. Recently, bioinformatic methods same as prediction algorithms, have greatly contributed to
the use of peptides in the design of immunogenic vaccines. Therefore, finding more conserved sites on the surface
glycoproteins (E1 and E2) of HCV, as major targets to design an effective vaccine against genetically different viruses
in each genotype was the goal of the study.
Materials and Methods:
In this experimental study, 100 entire sequences of E1 and E2 were retrieved from the NCBI
website and analyzed in terms of mutations and critical sites by Bioedit 7.7.9, MEGA X software. Furthermore, HCV-1a
samples were obtained from some infected people in Iran, and reverse transcriptase-polymerase chain reaction (RTPCR)
assay was optimized to amplify their E1 and E2 genes. Moreover, all three-dimensional structures of E1 and
E2 downloaded from the PDB database were analyzed by YASARA. In the next step, three interest areas of humoral
immunity in the E2 glycoprotein were evaluated. OSPREY3.0 protein design software was performed to increase the
affinity to neutralizing antibodies in these areas.
We found the effective in silico binding affinity of residues in three broadly neutralizing epitopes of E2
glycoprotein. First, positions that have substitution capacity were detected in these epitopes. Furthermore, residues
that have high stability for substitution in these situations were indicated. Then, the mutants with the strongest affinity
to neutralize antibodies were predicted. I414M, T416S, I422V, I414M-T416S, and Q412N-I414M-T416S substitutions
theoretically were exhibited as mutants with the best affinity binding.
Using an innovative filtration strategy, the residues of E2 epitopes which have the best in silico binding
affinity to neutralizing antibodies were exhibited and a distinct peptide library platform was designed.
Considering HER2 as one of the well-known biomarkers in the cancer field, and published articles regarding serum
levels of HER2, in this paper we tried to highlight the issue that most studies don’t stratify the HER-2 concentration
of individuals in terms of gender. In this brief survey, healthy individuals with no prior non-communicable diseases
were categorized as males (n=34) and females (n=43), and all samples were evaluated for plasma HER-2 levels
at once. Surprisingly, the plasma level of HER-2 of healthy male individuals (mean= 2.28 ± 0.21 ng/mL) was
significantly (P<0.0001) higher than the plasma level of HER-2 of healthy females (mean: 0.06 ± 0.09 ng/mL),
with no overlap. Therefore, we suggest that more studies are required to re-check the cutoff values for HER-2
plasma levels based on gender since the clinical implications of a unique HER-2 cutoff for both genders may be