Exosomes in renal cell carcinoma: challenges and opportunities.

Renal cell carcinoma (RCC) is the most common type of kidney cancer that accounts for approximately 2-3% of adult malignancies. Among the primary treatment methods for this type of cancer are surgery and targeted treatment. Still, due to less than optimal effectiveness, there are problems such as advanced distant metastasis, delayed diagnosis, and drug resistance that continue to plague patients. In recent years, therapeutic advances have increased life expectancy and effective treatment in renal cell carcinoma patients. One of these methods is the use of stem cells. Although the therapeutic effects of stem cells, especially mesenchymal stem cells, are still impressive, today, extracellular vesicles (EVs) as carrying molecules and various mediators in intercellular communications, having a central role in tumorigenesis, metastasis, immune evasion, and drug response, and on the other hand, due to its low immunogenicity and strong regulatory properties of the immune system, has received much attention from researchers and doctors. Despite the increasing interest in exosomes as the most versatile type of EVs, the heterogeneity of their efficacy presents challenges and, on the other hand, exciting opportunities for diagnostic and clinical interventions.In the upcoming article, we will review the various aspects of exosomes' effects in the prevention, treatment, and progress of renal cell carcinoma and also ways to optimize them to strengthen their positive sides.

Inhibitory potency of the nettle lectin on neovascularization: a biomolecule for carbohydrate-mediated targeting of angiogenesis.

BACKGROUND: Current angiogenesis inhibitors target cellular vascularization processes, including proliferation, migration, and tube formation. In this study, we investigated the impact of Urtica dioica agglutinin (UDA) on the cellular vascularization process. METHODS AND RESULTS: Various concentrations of UDA were applied to normal (HUVEC, MCF-10 A, and HDF from humans, and L-929 from mice) and cancer (A431 and U87 from humans, and 4T1 from mice) cell lines at different times. The MTT, cell migration assay, differentiation of endothelial cells, expression of VEGF-A/VEGF-R2, and integrin α2 were evaluated. The MTT results demonstrated that UDA was non-toxic to normal cells while inhibiting the growth of neoplastic cells. The migratory capacity of HUVECs and U87 glioblastoma cells was inhibited by UDA in the wound repair model. This lectin inhibited HUVEC-induced vessel sprouting in the collagen-cytodex matrix. In addition, UDA treatment reduced VEGF-integrin cross-talk in HUVECs, confirming the anti-angiogenic activity of this molecule. CONCLUSIONS: Based on our findings, UDA may have an effect on cancer cell proliferation and vascularization events while causing minimal toxicity to normal cells via binding glyco-conjugates containing GlcNAc/man oligomers like EGFR. This is a blue clue for the angiogenesis-related therapeutic importance of UDA.

The potential role of miR-1290 in cancer progression, diagnosis, prognosis, and treatment: An oncomiR or onco-suppressor microRNA?

Cancer is one of the leading causes of death in humans because of the lack of early diagnosis, distant metastases, and the resistance to adjuvant therapies, including chemotherapy and radiotherapy. In addition to playing an essential role in tumor progression and development, microRNAs (miRNAs) can be used as a robust biomarker in the early detection of cancer. MiR-1290 was discovered for the first time in human embryonic stem cells, and under typical physiological situations, plays an essential role in neuronal differentiation and neural stem cell proliferation. Its coding sequence is located at the 1p36.13 regions in the first intron of the aldehyde dehydrogenase 4 gene member A1. miR-1290 is out of control in many cancers such as breast cancer, colorectal cancer, esophageal squamous cell carcinoma, gastric cancer, lung cancer, pancreatic cancer, and plays a vital role in their development. Therefore, it is suggested that miR-1290 can be considered as a potential diagnostic and therapeutic target in many cancers. In addition to the importance of miR-1290 in the noninvasive diagnosis of various cancers, this systematic review study discussed the role of miR-1290 in altering the expression of different genes involved in cancer development and chemo-radiation resistance. Moreover, it considered the regulatory effect of natural products on miR-1290 expression and the interaction of lncRNAs by miR-1290.

Targeting endothelial cell metabolism in cancerous microenvironment: a new approach for anti-angiogenic therapy.

Anti-angiogenic therapy is a practical approach to managing diseases with increased angiogenesis, such as cancer, maculopathies, and retinopathies. Considering the fundamental gaps in the knowledge of the vital pathways involved in angiogenesis and its inhibition and the insufficient efficiency of existing angiogenesis inhibitors, there is an increasing focus on the emergence of new therapeutic strategies aimed at inhibiting pathological angiogenesis. Angiogenesis is forming a new vascular network from existing vessels; endothelial cells (ECs), vascular lining cells, are the main actors of angiogenesis in physiological or pathological conditions. Switching from a quiescent state to a highly migratory and proliferative state during new vessel formation called "angiogenic switch" is driven by a "metabolic switch" in ECs, angiogenic growth factors, and other signals. As the characteristics of ECs change by altering the surrounding environment, they appear to have a different metabolism in a tumor microenvironment (TME). Therefore, pathological angiogenesis can be inhibited by targeting metabolic pathways. In the current review, we aim to discuss the EC metabolic pathways under normal and TME conditions to verify the suitability of targeting them with novel therapies.

Diabetes complications and extracellular vesicle therapy.

Diabetes is a chronic disorder characterized by dysregulated glycemic conditions. Diabetic complications include microvascular and macrovascular abnormalities and account for high morbidity and mortality rates in patients. Current clinical approaches for diabetic complications are limited to symptomatic treatments and tight control of blood sugar levels. Extracellular vesicles (EVs) released by somatic and stem cells have recently emerged as a new class of potent cell-free therapeutic delivery packets with a great potential to treat diabetic complications. EVs contain a mixture of bioactive molecules and can affect underlying pathological processes in favor of tissue healing. In addition, EVs have low immunogenicity and high storage capacity while maintaining nearly the same regenerative and immunomodulatory effects compared to current cell-based therapies. Therefore, EVs have received increasing attention for diabetes-related complications in recent years. In this review, we provide an outlook on diabetic complications and summarizes new knowledge and advances in EV applications. Moreover, we highlight recommendations for future EV-related research.

Liposomes, new carriers for delivery of genes and anticancer drugs: a systematic review.

Today, nanoscience has grown and developed in various fields of medicine and treatment, including cancer treatment. Currently, the existing treatments, including chemotherapy and radiotherapy, cause side effects that are unpleasant to the patient. Due to the fact that anticancer drugs cause severe and widespread side effects, liposomes are considered as new drug carriers to minimize the untimely destruction of the drug when it is delivered to the target tissue and to prevent the side effects of toxic drugs. This systematic review study examined the importance of using liposomes as new drug carriers for the delivery of genes and anticancer drugs. The articles published in English in the databases of Google scholar, WoS, PubMed, Embase, Scopus and science direct were reviewed. According to the results of this study, a new targeted nanosystem has been used for loading and delivering anticancer drugs, genes and controlled drug release which has a significant therapeutic effect compared to the same amount of free drug. In general, liposomal systems have been considered because of their capability in preserving the effect of the drug along with reducing the side effects and toxicity of the drug, especially in the case of anticancer drugs. Accumulation of the drug in a target tissue which results in a reduction of the drug entry into other tissues is the main reason for reducing the side effects of these drugs.

A Turn Off Fluorescence Probe Based on Carbon Dots for Highly Sensitive Detection of BRCA1 Gene in Real Samples and Cellular Imaging.

In this research, DNA-modified carbon dots (CDs) were exploited to construct a fluorescence assay for breast cancer genes (BRCA1, a potential marker for cancer diagnosis) detection. For this purpose, water-soluble synthesized CDs were functionalized with 19 mer-modified oligonucleotides (capture probe). By adding the DNA target, the specific binding between the DNA probe and DNA target causes fluorescence quenching. The assay displayed a fine capability of sensing the BRCA1 gene with a linear range (R2 = 0.9918) of 36 attomolar (aM) to 532 femtomolar (fM) and a detection limit of 2 attomolar. This homogeneous process does not need additional separation and washing steps of un-hybridized DNA. To assess the selectivity, the prepared biosensor responses were evaluated in solutions containing single-base mismatched DNA sequences, three-base mismatched DNA sequences, or non-complementary DNA sequences, separately. To demonstrate the practical application of the designed biosensor, the extracted DNA from blood samples of breast cancer patients was utilized as real samples. When the CDs-DNA bioassay was exploited in the imaging of MCF-7 cancer cells, strong fluorescence emission was observed. After incubation times, both the cells' size and shape remained unchanged. The results validated that the CDs are an extremely great bioimaging candidate in disease diagnosis, biomedicine investigation, and managing cancer diseases.

Human placenta-derived mesenchymal stromal cells transfusion in a critically Ill infant diagnosed with Coronavirus Disease 2019 (COVID-19): A case report.

Coronavirus disease 2019 (COVID-19) is still an emergency in many countries. Herein, we report treatment with human placental-derived mesenchymal stromal cells transfusion (hPD-MSCT) in a critically ill infant diagnosed with COVID-19. A 28-day-old male infant with a history of pneumonia was referred to our center with decreased SpO2 (92%) and fever (38.5 °C). Real-time reverse transcription polymerase chain reaction (RT-PCR) and chest computed tomography (CT) confirmed COVID-19 infection. Considering the deteriorating clinical status of the patient despite the routine treatments (SpO2 82%), human placental derived mesenchymal stromal cells (hPD-MSCs) was transfused to him on day 9 and 11 (7 × 106 cells/session). The patient's general condition started to change 3 days after hPD-MSCT and poor feeding and low SpO2 improved day by day. On day 20, the patient was discharged (SpO2 97%) and our one-year follow-up showed a successful response to the treatment with no reported complications. hPD-MSCT may be considered as a possible treatment option in infants/children diagnosed with COVID-19 who fail to respond to conventional therapies. However, required dose, safety, and mechanistic studies are still warranted to further investigate this treatment.

Apoferritin nanocages for targeted delivery of idarubicin against breast cancer cells.

In recent years, nanotechnology has attracted attention for its capability to diagnose and remedy diverse tumors successfully.  Protein nanocarriers as a platform of targeted drug delivery can be used to reduce toxicity and improve the effect of anticancer drugs. Idarubicin (IDR) is a chemotherapy drug that is classified as an anthracycline antitumor. In this study, IDR was encapsulated within horse spleen apoferritin (HsAFr) nanocarriers. Encapsulation was obtained through disassembling apoferritin into subunits at pH 2 and subsequently reassembling it at pH 7.4 in the presence of IDR. Transmission electron microscopy, UV-vis, and fluorescence spectroscopy techniques showed that drug molecules are loaded within apoferritin. Intrinsic fluorescence information exhibited that the encapsulation does not have any effects on the tertiary structure of the protein. Drug loading and entrapment efficiency were found to be 7.15% and 84.75%, respectively. Comparison of anticancer activities in HsAFr-IDR and free drug IDR was made via the MTT viability technique in a human breast cancer cell line (MCF-7).

Carbon dots hybrid for dual fluorescent detection of microRNA-21 integrated bioimaging of MCF-7 using a microfluidic platform.

BACKGROUND: MicroRNAs have short sequences of 20 ~ 25-nucleotides which are similar among family members and play crucial regulatory roles in numerous biological processes, such as in cell development, metabolism, proliferation, differentiation, and apoptosis. RESULTS: We reported a strategy for the construction of a dual-emission fluorescent sensor using carbon dots (CDs) and confirmed their applications for ratiometric microRNA-21 sensing and bioimaging of cancer cells in a microfluidic device. The composition of blue CDs (B-CDs) and yellow CDs (Y-CDs) depicts dual-emission behavior which is centered at 409 and 543 nm under an excitation wavelength of 360 nm. With increasing microRNA-21 concentration, the robust and specific binding of DNA probe functionalized B-CDs to complementary microRNA-21 target induced perturbations of probe structure and led to changing fluorescence intensity in both wavelengths. Consequently, the ratio of turn-on signal to turn-off signal is greatly altered. With monitoring of the inherent ratiometric fluorescence variation (ΔF540nm/ΔF410nm), as-prepared BY-CDs were established as an efficient platform for ratiometric fluorescent microRNA-21 sensing, with a wide linear range of 0.15 fM to 2.46 pM and a detection limit of 50 aM. CONCLUSIONS: Furthermore, the proposed assay was applied for detecting microRNA-21 in dilute human serum samples with satisfactory recovery and also in MCF-7 cell lines in the range 3000 to 45,000 (cell mL-1) with a detection limit (3 cells in 10 µL), demonstrating the potential of the assay for clinic diagnosis of microRNA-associated disease. More importantly, the images revealed that MCF-7 cells well labeled with BY-CDs could exhibit the applicability of the proposed microfluidic system as an effective cell trapping device in bioimaging.

Fas cell surface death receptor/Fas ligand genetic variants in gastric cancer patients: A case-control study.

Background & objectives: Various studies have suggested a correlation between Fas cell surface death receptor/Fas ligand (FAS/FASL) variants and multiple types of cancers. The present study aimed to investigate the association between FAS-670A/G and FASL-844C/T and the synergistic effects of both variants on the risk of gastric cancer (GC) in the Kurdish population of west of Iran. Methods: This study was conducted by polymerase chain reaction-restriction fragment length polymorphism technique using MvaI and BsrDI restriction enzymes in 98 GC patients and 103 healthy control individuals. Results: According to the obtained results, a significant association (P=0.008) of FASL polymorphism among GC patients and the control group was detected. Furthermore, no significant differences were found in the FAS polymorphism frequencies between GC patients and the control group. Codominant and dominant models in FASL polymorphism showed significant protective effects against GC [odds ratio (OR)=0.307, 95% confidence interval (CI) (0.134-0.705), P=0.005; OR=0.205, 95% CI (0.058-0.718), P=0.013 and OR=0.295, 95% CI (0.129-0.673), P=0.004 for models of codominant CC vs. CT, codominant CC vs. TT and dominant, respectively]. Furthermore, the presence of both FAS-670G and FASL-844T alleles represented a significant protective effect against GC occurrence [OR=0.420, 95% CI (0.181-0.975), P=0.043]. Interpretation & conclusions: So far, we believe this is the first study, the results of which suggest that FASL gene variation and its synergistic effects with FAS gene could be associated with the risk of GC in the Kurdish population in the west of Iran.

Evaluation of co-cultured spermatogonial stem cells encapsulated in alginate hydrogel with Sertoli cells and their transplantation into azoospermic mice.

An in vitro spermatogonial stem cell (SSC) culture can serve as an effective technique to study spermatogenesis and treatment for male infertility. In this research, we compared the effect of a three-dimensional alginate hydrogel with Sertoli cells in a 3D culture and co-cultured Sertoli cells. After harvest of SSCs from neonatal mice testes, the SSCs were divided into two groups: SSCs on a 3D alginate hydrogel with Sertoli cells and a co-culture of SSCs with Sertoli cells for 1 month. The samples were evaluated by quantitative reverse transcription polymerase chain reaction (qRT-PCR) assays and bromodeoxyuridine (BrdU) tracing, haematoxylin and eosin (H&E) and periodic acid-Schiff (PAS) staining after transplantation into an azoospermic testis mouse. The 3D group showed rapid cell proliferation and numerous colonies compared with the co-culture group. Molecular assessment showed significantly increased integrin alpha-6, integrin beta-1, Nanog, Plzf, Thy-1, Oct4 and Bcl2 expression levels in the 3D group and decreased expression levels of P53, Fas, and Bax. BrdU tracing, and H&E and PAS staining results indicated that the hydrogel alginate improved spermatogenesis after transplantation in vivo. This finding suggested that cultivation of SSCs on alginate hydrogel with Sertoli cells in a 3D culture can lead to efficient proliferation and maintenance of SSC stemness and enhance the efficiency of SSC transplantation.

Endothelial cell dysfunction, coagulation, and angiogenesis in coronavirus disease 2019 (COVID-19).

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been led to a pandemic emergency. So far, different pathological pathways for SARS-CoV-2 infection have been introduced in which the excess release of pro-inflammatory cytokines (such as interleukin 1 ß [IL-1ß], IL-6, and tumor necrosis factor α [TNFα]) has earned most of the attentions. However, recent studies have identified new pathways with at least the same level of importance as cytokine storm in which endothelial cell (EC) dysfunction is one of them. In COVID-19, two main pathologic phenomena have been seen as a result of EC dysfunction: hyper-coagulation state and pathologic angiogenesis. The EC dysfunction-induced hypercoagulation state seems to be caused by alteration in the levels of different factors such as plasminogen activator inhibitor 1 (PAI-1), von Willebrand factor (vWF) antigen, soluble thrombomodulin, and tissue factor pathway inhibitor (TFPI). As data have shown, these thromboembolic events are associated with severity of disease severity or even death in COVID-19 patients. Other than thromboembolic events, pathologic angiogenesis is among the recent findings. Furthermore, over-expression/higher levels of different proangiogenic factors such as vascular endothelial growth factor (VEGF), hypoxia-inducible factor 1 α (HIF-1α), IL-6, TNF receptor super family 1A and 12, and angiotensin-converting enzyme 2 (ACE2) have been found in the lung biopsies/sera of both survived and non-survived COVID-19 patients. Also, there are some hypotheses regarding the role of nitric oxide in EC dysfunction and acute respiratory distress syndrome (ARDS) in SARS-CoV-2 infection. It has been demonstrated that different pathways involved in inflammation are generally common with EC dysfunction and angiogenesis. Altogether, considering the common possible upstream pathways in cytokine storm, pathologic angiogenesis, and EC dysfunction, it seems that targeting these molecules (such as nuclear factor κB) could be more effective in the management of patients with COVID-19.

How could perfluorocarbon affect cytokine storm and angiogenesis in coronavirus disease 2019 (COVID-19): role of hypoxia-inducible factor 1α.

Coronavirus disease 2019 (COVID-19) pandemic is still a world-class challenge. Inflammation, especially its severe form with excess release of pro-inflammatory cytokines (cytokine storm) which is a life-threatening condition, is among the most important suspects involved in COVID-19 pathogenesis. It has been shown that cytokine storm could cause notable morbidities such as acute respiratory distress syndrome (ARDS) which leads to hypoxia which is significantly associated with mortality of patients with COVID-19. Hypoxia-inducible factor 1α (HIF-1α) which activates following ARDS-induced hypoxia plays a crucial role in pathogenesis of cytokine storm. The expression of tumor necrosis factor α (TNF-α), interleukin 1 ß (IL-1ß), and IL-6 which are key elements of cytokine storm are by nuclear factor κß (NFκB). Interestingly, during the hypoxia, HIF-1α activates NFκB to induce expression of pro-angiogenic and pro-inflammatory factors. These released factors starts a autocrine/paracrine loop and causes deterioration of their etiological pathways of expression: cytokine storm and ARDS. To sum up, it seems HIF-1α is an important target to hit to ameliorate the mentioned pathways. Herein, we suggest perfluorocarbons (PFCs) which are among the organofluorine compounds as a possible co-treatment to reduce hypoxemia and then hypoxia. These substances are known for their high gas solving potential that make them able to be used as a synthetic artificial blood product. Due to the potential of PFCs to affect the fountain of important physiopathological pathway such as inflammation a hypoxia through affecting NFκB, they could be considered as multi-target co-treatment for ARD individuals with COVID-19. It is highly suggested to evaluate this hypothesis in following researches.

Association between PNPLA3 rs738409 polymorphism and nonalcoholic fatty liver disease: a systematic review and meta-analysis.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a common disorder that is known to be the leading cause of chronic liver disease worldwide. This study aims to systematically review and meta-analyze the association between PNPLA3 rs738409 polymorphism and non-alcoholic fatty liver. METHODS: Following a systematic review and meta-analysis method, articles without any time limitation, were extracted from SID, MagIran, IranDoc, Scopus, Embase, Web of Science (WoS), PubMed and ScienceDirect international databases. Random effects model was used for analysis, and heterogeneity of studies was investigated considering the I2 index and using Comprehensive Meta-Analysis software. RESULTS: The odds ratio of CC genotype in patients with non-alcoholic fatty liver demonstrates the protective effect of CC genotype with the ratio of 0.52, whereas CG genotype presents an increasing effect of CG genotype with the ratio of 0.19, and GG genotype also showed an increasing effect of GG genotype with the ratio of 1.05. Moreover, CG + GG genotypes as a single group demostrated an odds rartio of 0.88. CONCLUSION: This meta-analysis highlights that people with CC genotype has 52% lower chance of developing non-alcoholic fatty liver disease, and those with CG genotype had 19% higher risk of developing non-alcoholic fatty liver. Those with GG genotype were 105% more likely to develop non-alcoholic fatty liver than others. Moreover, those present in a population with CG + GG genotypes were 88% more likely to have non-alcoholic fatty liver disease.

Association between serum paraoxonase 1 activity and its polymorphisms with multiple sclerosis: a systematic review.

BACKGROUND: Human serum paraoxonase (PON) is an enzyme that is synthesized by the liver and enters the bloodstream, and it is transmitted by high-density lipoproteins (HDL). Paraoxonase 1 (PON1) is a hydrolytic enzyme with a wide range of substrates and the ability to protect against lipid oxidation. In this study, due to the activity of PON1 in the brain and its antioxidant effects on the reduction of neurological disorders in the central nervous system, the role of PON1 and its polymorphisms related to multiple sclerosis has been examined to enhance treatment methods. METHODS: This article is a systematic review. In this study, the role of PON1 and its polymorphisms in multiple sclerosis (MS) has been investigated. Articles published in Persian and international databases of SID, Google Scholar, ISI (WoS), Magiran, PubMed, Scopus, IranDoc, Science Direct, and Iran Medix were examined, using the search keywords of Paraoxonase 1, polymorphism, multiple sclerosis, and PON1. RESULTS: PON1 is undoubtedly a potential factor in the pathogenesis of multiple sclerosis, and it plays an important role in protecting antioxidants in the blood. Oxidative stress and lipid peroxidation are factors in the pathogenesis of MS. Both inflammatory cytokines and oxidative stress have a detrimental effect on PON1. However, reducing the activity of PON1 may help to restore the pathogenesis of the disease. CONCLUSION: Decreased PON1 activity and PON1 polymorphism are associated with several neurological diseases, including ischemic stroke, white matter lesions (WMLs), amyotrophic lateral sclerosis (ALS), dementia, and Parkinson's disease. PON1-55M alleles in Italians and PON1-192Q alleles in Poles were associated with a high risk of MS. Moreover, PON1-55 and PON1-192 polymorphisms were not associated with MS onset age, nor its evolutionary type.

The Agglutinin of Common Nettle (Urtica dioica L.) Plant Effects on Gene Expression Related to Apoptosis of Human Acute Myeloid Leukemia Cell Line.

Treatment of acute myeloid leukemia (AML) requires new drugs as result of a rise in new cases and high disease relapse. Plant lectins with the ability to bind carbohydrates on the cell surface have the potential to treat cancer. Urtica dioica L. agglutinin (UDA) is a low weight lectin with anti-benign prostatic hyperplasia (BPH) impact. Here, we examine the impact of UDA on HL-60 cell line. Cytotoxicity and cytostatic effects were assessed in HL-60 cells treated with UDA and vincristine (positive control). The effects of the lectin on cell cycle phases and cell death mechanism were surveyed by propidium iodide (PI) staining and annexin V/PI, respectively. The activation status of the apoptosis pathway was determined by western blotting. Finally, the expression levels of 84 genes were examined by the Human cancer drug target gene PCR array kit. The results indicated that the increase in UDA concentration inhibited the proliferation of HL-60 cells as well as apoptosis induction. Cell cycle analysis showed that the number of sub G1 cells increased essentially. Experimental observations showed that UDA can induce cell apoptosis through a caspase 9-dependent pathway. The expression changes of 21 genes confirmed the apoptotic events in HL-60 cells treated with UDA. In this, we have presented the first investigation on the cytotoxic and apoptotic effects of a lectin isolated from rhizomes and roots of Urtica dioica L. on human AML cells. Generally, the results suggest that UDA may have therapeutic value for leukemia and would be studied further as a new drug for AML later on.

Production of monoclonal antibody against recombinant bovine sex-determining region Y (SRY) and their preferential binding to Y chromosome-bearing sperm.

Separation of X and Y chromosome-bearing sperm is an appropriate method for the selection of desired sex of offspring to increase the profit in livestock industries. The purpose of this study was the production of a monoclonal antibody against recombinant bovine sex-determining region Y protein for separation Y sperm. The hybridoma cells from splenocytes of immunized female's balb/C mice and Sp2/0 cells were made. The binding affinity of our monoclonal antibody (mAbSRY2) was compared with mouse monoclonal SRY-15. The Western blot method indicated that mAbSRY2 successfully detected the rbSRY protein. The specificity and sensitivity of mAbSRY2 is comparable to SRY-15 commercially ones. The SRY gene in 100% of bull semen contains the Y chromosome that had the strongest binding affinity to mAbSRY2 was synthesized. In other words, the binding affinity of semen contains the X sperms near the negative control. In general, this immunological method can help to separate X from Y sperms. However, the mAbSRY2 is bind to Y-bearing sexed sperm, but in the future; the sexed sperms need to apply in farms.

Autophagy related gene expression status in patients diagnosed with azoospermia: A cross-sectional study.

BACKGROUND: Autophagy affects various aspects of the male reproductive system. Any defects in this process may lead to azoospermia. However, the exact molecular mechanisms of the autophagy pathway have remained largely obscure. Therefore, the present study aimed to investigate levels of autophagy pathway gene expression (i.e. Lc3B, Beclin1, ATG5 and Bcl2) in azoospermic patients. METHODS: The levels of Lc3B, Beclin1, ATG5 and Bcl2 mRNA expression in azoospermic patients and fertile males were evaluated by a real-time polymerase chain reaction technique. In addition, diagnostic evaluation based on the receiver-operating characteristic (ROC) curve was performed. RESULTS: The results obtained showed the decreased expression of Lc3B, Beclin1 and ATG5 genes in infertile patients compared to the control group (p < 0.05), whereas Bcl2 expression was increased in samples (p < 0.05). A diagnostic evaluation by ROC curve and calculation of the area under the curve showed that, using a cut-off relative quantification of 4.550, 0.052, 0.056 and 0.012, the sensitivity of Lc3B, Beclin1, ATG5 and Bcl2 genes was 87.5%, 93.8%, 93.8% and 90%, respectively. In addition, a specificity of 76.7%, 76.7%, 93.3% and 81.2%, respectively, was observed. CONCLUSIONS: As a first study, the current research suggests that an alteration in the expression of autophagy pathway genes may be associated with male infertility. Based on our finding, the increased expression of Bcl2 and formation of Becline1/Bcl2 complex, which inhibits Beclin1 recruitment, may lead to a decrease of the autophagy process in azoospermic patients. Accordingly, upon further investigation, the autophagy could be considered as an important aspect during spermatogenesis.

TSGA10 overexpression inhibits angiogenesis of HUVECs: A HIF-2α biased perspective.

Testis-specific gene antigen 10 (TSGA10) is a protein overexpressed in most cancers; except for some certain types where its expression is reduced. TSGA10 overexpression in HeLa cells has been shown to disrupt hypoxia inducible factor-1α (HIF-1α) axis and exert potent inhibitory effects. Since HIF-1α is structurally and biochemically similar to HIF-2α, TSGA10 is expected to bind HIF-2α and inhibit its function as well. This study elucidated that increased expression of TSGA10 in manipulated human umbilical vein endothelial cells (HUVECs) decreased the proliferation and migration of these cells as affirmed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and wound healing tests, respectively. It also inhibited in vitro angiogenesis of these cells in 3D collagen-cytodex model. Expression levels of genes controlled by HIF-2α including autocrine vascular endothelial growth factor (VEGF) were also assessed using real-time PCR. Our bioinformatic analysis also showed that TSGA10 could bind HIF-2α. Moreover, flow cytometry results indicated a cell cycle arrest in G2/M. Therefore, this study showed that overexpression of TSGA10, as a tumor suppressor gene, in endothelial cells resulted in decreased proliferation, migration and therefore, angiogenic activity of HUVECs. Since angiogenesis is vital for tumor development and metastasis, our findings could be of clinical significance in cancer therapy.