Cell Journal (Yakhteh)
Volume:23 Issue: 5, Oct 2021

Sperm associated antigens (SPAGs) are specific proteins in terms of performance and evolution, that have common expressions in the testes or sperm cells. Moreover, the humoral immune response against some of SPAGs can result in immunological infertilities. On the other hand, recent studies have explored several new properties of SPAGs and shed light on sperm's function, the impact of anti-sperm antibodies (ASA) in immunological infertility, and some tumors related to SPAGs. This article presents an exhaustive review of SPAGs and their roles in the cell cycle, signaling pathways, fertility, sperm-oocyte cross-talk as well as their unfavorable positions as prognostic factors in many types of cancers.

Multiple myeloma (MM) is the clonal proliferation of neoplastic plasma cells in the bone marrow. Although bortezomib (BTZ) is a crucial drug for the treatment of MM, drug resistance is a major problem. OncomiR-19a plays an oncogenic role in many cancers, including MM; however, the function of miR-19a in the pathogenesis of MM and drug resistance has not been completely identified. The present research aims to investigate the inhibition of miR-19a by an antagomir to determine BTZ responsiveness, and determine if miR-19a can be a prognostic biomarker for MM.

In this experimental study, viability and apoptosis of myeloma cells were analysed by the colorimetric 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-Diphenyltetrazolium Bromide (MTT) and Annexin V/propidium iodide (PI) flow cytometry assays. Quantitative real-time polymerase chain reaction (qRT-PCR) was implemented to evaluate the expression levels of miR-19a, its targets SOCS3, STAT3, B-cell lymphoma 2 (BCL-2), PTEN and CDKN1A (antiapoptotic and cell cycle related genes) at the mRNA level.

miR-19a was downregulated and exacerbated in transfected cells treated with BTZ. The rate of apoptosis in the myeloma cells after BTZ treatment considerably increased, which indicated an increase in the mRNA of SOCS3, PTEN, BCL-2, and CDKN1. A decrease in STAT3 was also observed.

OncomiR-19a, as a biomarker, may induce better responsiveness to BTZ in myeloma cell lines through its targets SOCS3, STAT3 and PTEN. In the future, this biomarker may provide new therapeutic targets for MM.

Growth factors [transforming growth factor-β (TGF-β), epidermal growth factor (EGF), endothelin-1 (ET- 1)] stimulate proteoglycan synthesis resulting in retention and accumulation of low density lipoprotein (LDL) in vessel intima and leading to atherosclerosis development. This study investigated the role of ET-1 on the expression of CHSY1, proteoglycan synthesizing enzyme, through both EGF and TGF-β receptor transactivation in human vascular smooth muscle cells (VSMCs). Also, we explored the involvement of NADPH oxidase (NOX), an important intermediate of redox signaling, in ET-1 transactivated EGF receptor (EGFR) through endothelin receptors.

In this experimental study, phosphorylated ERK1/2 and CHSY1 protein levels in the human VSMCs were measured by Western blot analysis using anti phospho-ERK1/2 (Thr202/Tyr204) and anti CHSY1 antibodies.

ET-1 (100 nM) and EGF (100 ng/ml) stimulated ERK1/2 phosphorylation and inhibited in the presence of bosentan (ET receptor inhibitor), AG1478 (EGFR inhibitor), and DPI (NOX antagonist). Also, ET-1 treatment increased CHSY1 enzyme level; this response was suppressed by bosentan, AG1478, DPI, and SB431542, TGF-β receptor antagonist. This study revealed that ET-1 increases expression of CHSY1 through transactivation of EGF and TGF-β receptors.

Transactivation through the EGF receptor mediated by phospho-ERK1/2 leads to expression of CHSY1 protein. EGF receptor transactivation by ET-1 is shown for the first time, to be dependent on NOX enzymes.

Trimethylamine-N-Oxide (TMAO) is considered as a risk factor for atherosclerosis which further leads to inflammation during atherosclerosis. The exact mechanism(s) by which TMAO induces the inflammatory reactions remains to be determined. TMAO can cause the endoplasmic reticulum (ER) stress that triggers activation of Toll-Like Receptors (TLRs). In macrophages, this process stimulates the production of proinflammatory cytokines. This study designed to evaluate the expression level of TLR4 in TMAO-treated macrophages.

In this experimental study, different concentrations of TMAO (37.5, 75, 150, and 300 μM) were exposed to murine macrophage (J774A.1 cell line) for 8, 18, 24, and 48 hours. The cells were also treated with 2.5 mM of 4-phenyl butyric acid as well as 2μg/ml of tunicamycin respectively as negative and positive controls for inducing ER-stress. We measured the viability of treated cells by the MTT test. Besides, the expression levels of TLR4 gene and protein were evaluated using western blotting and reverse transcription- quantitative polymerase chain reaction (RT-qPCR) analysis. One-Way ANOVA was used for statistical analysis.

No cell death was observed in treated cells. The cells treated with 150 and 300 μM doses of TMAO for 24 hours showed a significant elevation in the protein and/or mRNA levels of TLR4 when compared to normal control or tunicamycin-treated cells.

Our results may in part elucidate the mechanism by which TMAO induces the macrophage inflammatory reactions in response to the induction of ER stress, similar to what happens during atherosclerosis. It also provides documentation to support the direct contribution of TLR4 in TMAO-induced inflammation.

We performed this bibliometric analysis to identify global scientific research on the SARS-CoV-2 vaccines.

This bibliometric analysis study inclusive search of English-language publications related to the SARS-CoV-2 vaccines was conducted in the Scopus, PubMed, and Dimensions databases without year limitations. The results of bibliometric analysis comprised a time-dependent citation density trend, the name of the journal, journal impact factor (IF), year of publication, type of article, category, subscription or affiliation, co-authorship, and cooccurrence network.

A study of the scientific literature from three databases (Scopus, PubMed, Dimensions) shows that investigators have focused more on studying the structure of the coronavirus at different levels (organismic, cellular, and molecular). In addition, the method of virus penetration into the cell and features of the influence of coronavirus on animals are well-studied. Various methods and strategies are being used to develop the vaccines, including both animal-tested methods and computer models. The Dimensions database is the most representative in terms of coverage of research on development of the SARS-CoV-2 vaccines.

This research is a scientific investigation based on bibliometric analysis of papers related to the SARS-CoV-2 vaccines. The Dimensions database provides the most representative research coverage on the creation of a vaccine against coronavirus. It is characterized by a large number of formed verbose terms (length of more than four words) related to coronavirus, which makes it possible to track trends in the development of methods for creating a vaccine.

Ionizing radiation is a tremendous risk factor for cancer development. MicroRNAs (miRNAs) are regulators that utilize cell pathways, which are implicated in human cancer prognosis. In addition, miRNAs respond to anti-cancer therapy and proliferation after irradiation. However, the changes in miRNA expression profiles in response to irradiation have not been comprehensively analysed. The present study was designed to assess potential changes that occur in miRNA expression following irradiation.

In this experimental study, we used quantitative real-time polymerase chain reaction (qRTPCR) to measure the expressions of miR-155, miR-21, and let-7a in MCF-10A (normal breast cells) and MCF-7 (breast cancer cells) six hours after the cells were exposed to five different irradiation doses (50, 100, 400, 2000, and 4000 mGY).

After irradiation from the low to high doses, we observed an upsurge in miR-155 (more than 100%) expression and reduction in let-7a (more than 87%) expression. However, there was an increase and a reduction in miR-21 expression (more than 100%).

Irradiation can play an important role in cancer development in normal breast cells (MCF-10A) at low dose irradiation. However, the results showed little difference at high doses of radiation.

Methadone is one of the widely used drug substances prescribed in treatment of opioid dependence and pain management; however, several studies have shown its neurotoxic effects on individuals and animal models. The purpose of this study was to assess neuroprotective effects of Coenzyme Q10 (CoQ10) on neurotoxicity induced by methadone in hippocampus of adult NMRI male mice.

In this experimental study, 48 adult NMRI male mice were randomly divided into 4 groups (n=12 in each) including Methadone, Methadone with sesame oil, Methadone with CoQ10 and saline. The injections of methadone, saline and sesame oil were performed intraperitoneally for 20 days. 24 hours after last injection, half of the animals in each group (n=6) were randomly assessed for evaluating of spatial memory by radial maze. Following behavioral study, animals were sacrificed, and their brains were removed to evaluate pyknotic cells through histological assessment. The remaining were used to study the expression of Arc, Bax, Bcl-2 and Bdnf genes.

Results of the present study showed that daily administration of methadone increased the number of pyknotic neurons in the CA1 hippocampus and altered the expression of Bax, Bdnf, Arc and Bcl-2. However, it did not alter spatial memory comparing to saline group. CoQ10 treatment significantly reduced the number of pyknotic cells and expression of Bax, Bdnf, Arc when compared to the vehicle group treated by sesame oil. However, the expression of Bcl-2 significantly increased as a result of CoQ10 treatment.

CoQ10 reduced the neuronal damage caused by methadone in the hippocampus CA1.

In cancer treatments, smart gene delivery via nanoparticles (NPs) can be targeted for cancer cells, while concurrently minimizing damage to healthy cells. This study assessed the efficiency of poly lactic-co-glycolic acid (PLGA)-miR 143/206 transfection on apoptosis in mouse leukemia cancer cells (El4) and spermatogonial stem cells (SSCs).

In this experimental study, neonatal mouse spermatogonia cells and EL4 cancer cell lines were used. MicroRNA-PLGA NPs were prepared, characterized, and targeted with folate. Several doses were evaluated to obtain a suitable miR dose that can induce appropriate apoptosis in EL4 cells, while not harming SSCs. Cells were treated separately at 3 doses of each miR (for miR 143, doses of 25, 50 and 75 nmol and for miR 206, doses of 50, 100 and 150 nmol). The experiments were performed at 24, 48 and 72 hours. Viability and apoptosis were investigated by MTT and Annexin Kits.

Based on MTT assay results, the optimal dose of miR 143 was 75 nmol (59.87 ± 2.85 % SSC and 35.3 ± 0.78 % EL4) (P≤0.05), and for miR 206, the optimal dose was 150 nmol (54.82 ± 6.7 % SSC and 33.92 ± 3.01% EL4) (P≤0.05). The optimal time was 48 hours. At these doses, the survival rate of the EL4 cells was below the half maximal inhibitory concentration (IC50) and SSC survival was above 50%. Annexin V staining also confirmed the selected doses (for miR 143 total apoptosis was 6.62% ± 1.8 SSC and 37.4% ± 4.2 EL4 (P≤0.05), and miR 206 was (10.98% ± 1.5 SSC and 36.4% ± 3.7 EL4, P≤0.05).

Using intelligent transfection by NPs, we were able to induce apoptosis on EL4 cells and maintain acceptable SSC survival rates.

There is growing evidence showing that circular RNAs (circRNAs) are crucial regulators in modulating the biological behavior of tumors. This work is aimed to probe the role of circ_0000517 in non-small cell lung cancer (NSCLC) and to elucidate its mechanism of action.

In this experimental study, the differentially expressed circRNAs in NSCLC were screened using the GEO database (GSE158695). Circ_0000517, miR-326, miR-330-5p, and MMP2 expression levels were determined by quantitative real-time polymerase chain reaction (qRT-PCR) analysis and Western blot. The proliferation, apoptosis, migration, and invasion of NSCLC cells were detected by CCK-8, flow cytometry, and transwell assays. RNA immunoprecipitation (RIP), RNA pull-down, and dual-luciferase reporter gene assays were performed to clarify the association between the circ_0000517 and miR-326/miR-330-5p.

Circ_0000517 was shown to be up-regulated in NSCLC tissues and cell lines. The up-regulation of circ_0000517 is closely associated with advanced clinical stage of cancer, lymph node metastasis, and poor prognosis in NSCLC patients. Circ_0000517 knockdown impeded the proliferation, migration, and invasion of NSCLC cells and enhanced their apoptosis. Mechanistically, circ_0000517 was demonstrated to up-regulate MMP2 expression via decoying miR-326 and miR-330-5p to facilitate the malignant biological behaviors of NSCLC cells.

This work reveals that circ_0000517 is implicated in NSCLC cell growth and metastasis through the modulation of miR-326/miR-330-5p/MMP2, providing novel insights into the role of circRNAs in NSCLC progression.

There is growing evidence showing that circular RNAs (circRNAs) are crucial regulators in modulating the biological behavior of tumors. This work is aimed to probe the role of circ_0000517 in non-small cell lung cancer (NSCLC) and to elucidate its mechanism of action.

In this experimental study, the differentially expressed circRNAs in NSCLC were screened using the GEO database (GSE158695). Circ_0000517, miR-326, miR-330-5p, and MMP2 expression levels were determined by quantitative real-time polymerase chain reaction (qRT-PCR) analysis and Western blot. The proliferation, apoptosis, migration, and invasion of NSCLC cells were detected by CCK-8, flow cytometry, and transwell assays. RNA immunoprecipitation (RIP), RNA pull-down, and dual-luciferase reporter gene assays were performed to clarify the association between the circ_0000517 and miR-326/miR-330-5p.

Circ_0000517 was shown to be up-regulated in NSCLC tissues and cell lines. The up-regulation of circ_0000517 is closely associated with advanced clinical stage of cancer, lymph node metastasis, and poor prognosis in NSCLC patients. Circ_0000517 knockdown impeded the proliferation, migration, and invasion of NSCLC cells and enhanced their apoptosis. Mechanistically, circ_0000517 was demonstrated to up-regulate MMP2 expression via decoying miR-326 and miR-330-5p to facilitate the malignant biological behaviors of NSCLC cells.

This work reveals that circ_0000517 is implicated in NSCLC cell growth and metastasis through the modulation of miR-326/miR-330-5p/MMP2, providing novel insights into the role of circRNAs in NSCLC progression.

Acute kidney injury (AKI) is referred to as sudden decline in the function of kidney. Human endometrial stromal/stem cells (hEnSCs) are mesenchymal stem cell (MSC)-like cells, which are suitable candidates for regenerative medicine purposes, yet the effect of hEnSCs on cisplatin-induced AKI has not been studied; therefore, the present study was conducted to investigate this gap in the literature.

In this experimental study, hEnSCs were obtained from endometrial biopsy using collagenase I and were then cultured in DMEM/F12 medium. A total of 48 male Wistar rats (150-200 g) were classified into four groups: intact -receiving no treatment, model -receiving 5 mg/kg of body weight cisplatin, as well as phosphate-buffered saline (PBS) and cell -receiving either PBS or hEnSCs for three hours after cisplatin injection, respectively. Biochemical parameters, pathologic scores, apoptosis assay, Bcl-2 and Tnf-α expression were evaluated on day 5.

On day 5 post-transplantation we observed that HEnSCs injection has led to a decrease in both blood urea nitrogen (BUN) and serum creatinine (SCr), compared to the model and PBS groups (0.82 ± 0.03 vs. 1.42 ± 0.06, 1.09 ± 0.05 mg/dl and 61.53 ± 3.07 vs. 116.60 ± 2.12, 112.00 ± 1.35 mg/dl, respectively). The highest levels of pathologic scores were observed in model and PBS groups, while hEnSCs transplantation resulted in a decrease in pathologic scores (149.10 ± 7.03, 141.50 ± 4.68 vs. 118 ± 2.16). HEnSCs significantly decreased the percentage of TUNELpositive cells in the cell group compared with model and PBS groups (20.37 ±. 3.37 vs. 33.67 ± 1.79, 31.53 ± 1.05 in glomeruli and 15.10 ± 1.47 vs. 42.33 ± 1.72, 39.23 ± 1.61 in tubules). In addition, HEnSCs resulted in upregulation of Bcl-2 and downregulation of Tnf-α in the cisplatin-induced AKI.

Our results showed that injection of hEnSCs may improve AKI through lowering the amount of apoptosis in renal cells.

Hair loss is a prevalent medical problem in both men and women. Maintaining the hair inductivity potential of human dermal papilla cells (hDPCs) during cell culture is the main issue in hair follicle morphogenesis and regeneration. The present study was conducted to compare the effects of different concentrations of exosomes derived from human adipose stem cells (hASCs) and platelet-rich plasma (PRP) on the proliferation, migration and expression of alkaline pholphatase (ALP), versican, and smooth muscle alpha-actin (α-SMA) in human DPCs.

In this experimental study, hDPCs, human hair DPCs and outer root sheet cells (ORSCs) were separated from healthy hair samples. The protocol of exosome isolation from PRP and hASCs comprises serial low speed centrifugation and ultracentrifugation. The effects of different concentrations of exosomes (25, 50, 100 μg/ ml) derived from hASCs and PRP on proliferation (MTS assay), migration (scratch test) and expression of ALP, versican and α-SMA (real time-polymerase chain reaction) in human DPCs were evaluated.

The flow cytometry analysis of specific cytoplasmic markers showed expression of versican (77%) and α-SMA (60.8%) in DPCs and K15 (73.2%) in ORSCs. According to NanoSight Dynamic Light Scattering, we found the majority of ASCs and PRP-exosomes (ASC-Exo and PRP-Exo) to be 30-150 nm in size. For 100 μg/ml of ASCs-Exo, the expressions of ALP, versican and α-SMA proteins increased by a factor of 1.2, 2 and 3, respectively, compared to the control group. The findings of our experiments illustrated that 100 μg/ml of ASCs-Exo compared to the same concentration of PRP-Exo significantly promote DPC proliferation and migration in culture.

This study introduced the potential positive effect of ASC-Exo in increasing the proliferation and survival of DPCs, while maintaining their hair inductivity. Thus, ASCs-Exo possibly provide a new effective procedure for treatment of hair loss.

The aim of this study was to evaluate the effect of lysophosphatidic acid (LPA) on the follicular development, incidence of cell death, and expressions of apoptosis related genes and miR-22 in transplanted ovaries.

In this experimental study, three-week-old mice ovaries were cultured for 24 hours in the presence and absence of LPA, and we assessed cell survival and normal follicular rates in some of the cultured ovaries. The remaining cultured ovaries were autotransplanted in the presence and absence of LPA as four experimental groups (LPA-/LPA-, LPA-/LPA+, LPA+/LPA-, LPA+/LPA+). The follicular development, immunohistochemistry for BAX, and expressions of genes related to apoptosis and miR-22 by real time reverse transcription polymerase chain reaction (RTPCR) were studied at the first oestrous cycles in the recovered ovaries. Sera 17-β-oestradiol (E2) and progesterone (P4) levels were also assessed.

Both cell survival and normal follicular rates were significantly higher in cultured ovaries in the presence of LPA after 24 hours (P<0.05). There was an increase in follicular development in comparison with the intact control group in the four transplanted groups (P<0.05). The LPA+/LPA- group had significantly higher follicular development, a decline in BAX positive cells, and a decrease in pro-apoptotic gene expressions in parallel with enhanced expression of anti-apoptotic and miR-22 genes and higher levels of hormones compared with the non-treated and intact control groups (P<0.05).

LPA, as a survival factor, improves follicular development in transplanted ovaries by providing a balance between the anti- and pro-apoptotic genes in association with an increase in miR-22 expression.

Congenital disorders of glycosylation (CDG) are a heterogeneous group of systemic disorders characterized by defects in glycosylation of lipids and proteins. One of the rare subtypes of CDG is CDG-Ij (MIM # 608093), which is caused by pathogenic mutations in DPAGT1, a gene encoding UDP-N-acetylglucosaminedolichyl-phosphate N-acetylglucosaminephosphotransferase enzyme. This enzyme catalyzes the first step of oligosaccharide synthesis in glycoprotein biosynthesis pathway. Preimplantation genetic testing for monogenic disorders (PGT-M) is a diagnostic technique that can reveal the genetic profile of embryos before implantation phase of in vitro fertilization (IVF). Currently, this approach is performed using next generation sequencing (NGS) technology. Herein, with the help of whole-exome and Sanger sequencing, we detected a novel missense mutation (NM_001382, c.1217 A>G) in DPAGT1 gene in two families with consanguineous marriage. Using different online bioinformatics tools including MutationTaster, I-Mutant v2.0, T- Coffee, and CADD v1.0, this mutation was predicted pathogen. Finally, after performing PGT-M followed by successful pregnancy, a normal child was born in one of these families. In conclusion, we identified a novel pathogenic mutation in DPAGT1 in a family with multiple members affected by CDG, which extends the range of pathogenic variants associated with CDG and therefore facilitates early detection of the disease.

In this study, we describe one Iranian patient who was diagnosed with Epidermolysis Bullosa (EB) because of mutations in three candidate genes, including 3 mutations. Two missense mutations in the LAMA3 (D3134H) and LAMB3 (Y339H) genes and also, a synonymous mutation in the ITGB4 (H422H) gene were identified that leads to the Junctional-EBHerlitz (JEB-Herlitz) clinical phenotype. The patient had a heterozygous LAMA3 mutation combined with a heterozygous mutation in LAMB3. Our results propose that these mutations produce novel protein-coding transcripts which explain the JEB-Herlitz phenotype in the patient. Interestingly, this is the first report indicating that a digenic inheritance in the LAMA3 and LAMB3 which is responsible for JEB-Herlitz. Also, this is the first digenic inheritance recognized in the JEB-Herlitz family. This study provides a new way to clarify the molecular mechanisms of LAMA3 and LAMB3 genes in JEB-Herlitz.