Recent advances in gene delivery nanoplatforms based on spherical nucleic acids.

Gene therapy is a therapeutic option for mitigating diseases that do not respond well to pharmacological therapy. This type of therapy allows for correcting altered and defective genes by transferring nucleic acids to target cells. Notably, achieving a desirable outcome is possible by successfully delivering genetic materials into the cell. In-vivo gene transfer strategies use two major classes of vectors, namely viral and nonviral. Both of these systems have distinct pros and cons, and the choice of a delivery system depends on therapeutic objectives and other considerations. Safe and efficient gene transfer is the main feature of any delivery system. Spherical nucleic acids (SNAs) are nanotechnology-based gene delivery systems (i.e., non-viral vectors). They are three-dimensional structures consisting of a hollow or solid spherical core nanoparticle that is functionalized with a dense and highly organized layer of oligonucleotides. The unique structural features of SNAs confer them a high potency in internalization into various types of tissue and cells, a high stability against nucleases, and efficay in penetrating through various biological barriers (such as the skin, blood-brain barrier, and blood-tumor barrier). SNAs also show negligible toxicity and trigger minimal immune response reactions. During the last two decades, all these favorable physicochemical and biological attributes have made them attractive vehicles for drug and nucleic acid delivery. This article discusses the unique structural properties, types of SNAs, and also optimization mechanisms of SNAs. We also focus on recent advances in the synthesis of gene delivery nanoplatforms based on the SNAs.

miRNAs that regulate apoptosis in breast cancer and cervical cancer.

In today's world, one of the main problems is cancer, which still has a long way to go to cure it, and it brings a lot of financial and emotional costs to the people of society and governments. Breast cancer (BC) and cervical cancer (CC), two of the most common cancers, are caused by several genetic and environmental factors in women. These two cancers' involvement rate is higher than other cancers in women. microRNAs (miRNAs) are non-coding RNA molecules with a length of 18 to 24 nucleotides, which play an important role in post-translational changes. miRNAs themselves are divided into two categories, oncomiRs and tumor suppressors. OncomiRs have a part in tumor expansion and tumor suppressors prevent tumor development and progress. miRNAs can control cellular processes by regulating various pathways including autophagy, apoptosis, and signaling. Apoptosis is a type of programmed cell death that includes intrinsic and extrinsic pathways and is different from other cell death pathways such as necrosis and ferroptosis. Apoptosis controls the growth, differentiation, and death of cells by regulating the death of damaged and old cells, and since miRNAs are one of the factors that regulate apoptosis, and divided into two categories: pro-apoptotic and anti-apoptotic. We decided in this study to investigate the relationship between miRNAs and apoptosis in the most common women's cancers, BC and CC.

Investigating SNHG3 and BCYRN1 lncRnas expression in the peripheral blood cells of multiple sclerosis patients.

BACKGROUND: MS (Multiple sclerosis) is a progressive neurologic disorder often appearing in the third decade of life. MS is the most frequent demyelinating disease of the central nervous system. The development of MS is influenced by environmental, genetic, and epigenetic factors. The bulk of the human transcriptome comprises lncRNAs, which play crucial regulatory roles. We aimed to assess the SNHG3 and BCYRN1 lncRNA expression in blood samples from MS patients and how these lncRNAs and disease activity are related. METHODS: A total of 100 MS patients, including 8 primary progressive (PP), 82 relapsing-remitting (RR), and 10 secondary progressive (SP) MS, as well as 100 healthy controls, had their blood samples taken. Gene expression was assessed using quantitative real-time PCR. Recognizing the receiver operating characteristic (ROC) curve analysis, the diagnostic potential of lncRNA levels was evaluated. RESULTS: Expressions of SNHG3 and BCYRN1 were found to have significantly increased (p < 0.0001). SNHG3 expression level showed significant differences compared to age groups and MS subtypes (p value = 0.001 and p value = 0.02).Furthermore, patients with a family history showed elevated BCYRN1 expression with a p value of 0.01. Considering the age factor, BCYRN1 exhibits altered expression levels in patient groups compared to healthy controls (p value 0.04). Additionally, the novel biomarkers SNHG3 and BCYRN1 can be used to diagnose MS (AUC = 0.97 and AUC = 0.88, respectively). DISCUSSION: Increased levels of SNHG3 and BCYRN1 in the serum may serve as potential molecular biomarkers for the MS diagnosis.

Dysregulated expression of IGSF11-AS1 and BVES-AS in azoospermia and its correlation with serum hormone levels.

Aim: Azoospermia accounts for 10-20% of male infertility. In 20-30% of affected males, genetic abnormalities are the leading cause of azoospermia. LncRNAs can regulate spermatogenic cell development. Methods: This study chose 76 azoospermia patients and 36 healthy males. The gene expression was examined using the qRT-PCR technique. Results: IGSF11-AS1 and BVES-AS appeared to be considerably underexpressed in the patients; however, only IGSF11-AS1 demonstrated a significant biomarker role. Additionally, IGSF11-AS1 expression was positively correlated with testosterone but was negatively correlated with follicle-stimulating hormone (FSH) and luteinizing hormone (LH). For the BVES-AS gene, however, FSH and LH had a negative correlation. Conclusion: As a result of its low expression level in tissue samples, IGSF11-AS1 has a biomarker role for early azoospermia detection.

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Investigating the effect of LncRNA DLGAP1-AS2 suppression on chemosensitivity of gastric cancer to chemotherapy.

Gastric cancer, as the fifth most frequent disease and the fourth foremost cause of cancer-related death worldwide, remains a main clinical challenge due to its poor prognosis, limited treatment choices, and ability to metastasize. Combining siRNAs to suppress lncRNA with chemotherapeutic medications is a novel treatment approach that eventually increases the therapeutic efficacy of the drug while lessening its adverse effects. This study was performed with the purpose of examining the impact of inhibiting DLGAP1-AS2 expression on gastric cancer cells' drug chemosensitivity. AGS cells were cultured as the study cell line and were transfected with an optimum dose of DLGAP1-AS2 siRNA and then treated with oxaliplatin. Cell viability was examined using the MTT technique. Apoptosis and cell cycle were evaluated using Annexin V/PI staining and flow cytometry. Later, the scratch test was conducted to investigate the ability of cells to migrate, and the inhibition of the stemness of AGS cells was further investigated through the colony formation method. Finally, the qRT-PCR technique was used to assess the expression of Bax, Bcl-2, Caspase-3, p53, MMP-2, and CD44 genes. The MTT test indicated the effect of gene therapy with siRNA and oxaliplatin in combination reduced the chemotherapy drug dose to 29.92 µM and increased AGS cells' sensitivity to oxaliplatin. Also, the combination therapy caused a significant increase in apoptosis. However, it reduced the stemness feature, the rate of cell viability, proliferation, and metastasis compared to the effect of each treatment alone; the results also showed the arrest of the cell cycle in the Sub G1 phase after the combined treatment and a further reduction in the number and size of the formed colonies. Suppressing the expression of lncRNA DLGAP1-AS2 by siRNA followed by treatment with oxaliplatin can be utilized as an effective and new therapeutic technique for gastric cancer therapy.

miRNA-21, an Important Regulator of Autoimmune Diseases.

miRNA-21 is regarded as both an abundant and highly conserved member of the microRNA (miRNA) family. It is expressed in virtually every cell and is responsible for critical regulatory actions that are important in health and disease. This microRNA has been shown to potentially have a role in the pathogenesis of several immune-related disorders, including autoimmune diseases, such as Multiple sclerosis and systemic lupus erythematosus, as two prominent examples of diseases that might be involved. In the current research, we looked at the role of miRNA-21, regarded as one of the most significant pathogenic miRNAs with a role in the development of autoimmune illness.

The potential use of nanozymes as an antibacterial agents in oral infection, periodontitis, and peri-implantitis.

Several studies suggest that oral pathogenic biofilms cause persistent oral infections. Among these is periodontitis, a prevalent condition brought on by plaque biofilm. It can even result in tooth loss. Furthermore, the accumulation of germs around a dental implant may lead to peri-implantitis, which damages the surrounding bone and gum tissue. Furthermore, bacterial biofilm contamination on the implant causes soft tissue irritation and adjacent bone resorption, severely compromising dental health. On decontaminated implant surfaces, however, re-osseointegration cannot be induced by standard biofilm removal techniques such as mechanical cleaning and antiseptic treatment. A family of nanoparticles known as nanozymes (NZs) comprise highly catalytically active multivalent metal components. The most often employed NZs with antibacterial activity are those that have peroxidase (POD) activity, among other types of NZs. Since NZs are less expensive, more easily produced, and more stable than natural enzymes, they hold great promise for use in various applications, including treating microbial infections. NZs have significantly contributed to studying implant success rates and periodontal health maintenance in periodontics and implantology. An extensive analysis of the research on various NZs and their applications in managing oral health conditions, including dental caries, dental pulp disorders, oral ulcers, peri-implantitis, and bacterial infections of the mouth. To combat bacteria, this review concentrates on NZs that imitate the activity of enzymes in implantology and periodontology. With a view to the future, there are several ways that NZs might be used to treat dental disorders antibacterially.

Upregulation of Long Noncoding RNA PCAT1 in Iranian Patients with Colorectal Cancer and Its Performance as a Potential Diagnostic Biomarker.

Background: Long noncoding RNAs (lncRNAs) as critical molecules play an essential role in the development of cancers. In colorectal cancer (CRC), various lncRNAs are related to cell proliferation, apoptosis, migration, and invasion. LncRNA prostate cancer-associated transcript 1 (PCAT-1), as an oncogenic factor, is a diagnostic biomarker that regulates cell proliferation, migration, invasion, and apoptosis. Methods: This study evaluated the relationship between PCAT-1, CRC occurrence, and pathological features of Iranian patients. The studied samples included 100 colorectal tumor tissues and 100 adjacent healthy tissues of Iranian CRC patients. RNAs were extracted from cancerous and noncancerous tissues to synthesize complementary DNA. The expression level of PCAT-1 was assessed using the real-time PCR method, and the data analysis was assessed using SPSS software. Results: In this study, expression level of PCAT-1 in tumor tissue was significantly increased in Iranian patients, and pathological studies of the patients had no significant relationship with the PCAT-1 expression profile. Conclusion: Our results suggested that the high expression of PCAT-1 resulted in the occurrence of colorectal tumor tissues in Iranian patients, which can be considered a diagnostic biomarker in CRC.

Investigating the Effect of Internal Bleaching With 10% Carbamide Peroxide on the Color Change of Three Types of Common Endodontic Sealers.

Background and purpose Color change caused by materials used for endodontic treatment is an important clinical issue. The current research examined the impact of internal bleaching with 10% carbamide peroxide on discolored teeth resulting from various types of sealers. Materials and methods In this study, 36 anterior teeth were cut from 1 mm beneath the cementoenamel junction (CEJ), and the samples were divided into three groups of 12. Then, AH26 (Tulsa Dental, Tulsa, OK), Endofill (Herpo Produtos Dentários Ltda, Petrópolis, Brazil), and AH Plus (Dentsply DeTrey, Konstanz, Germany) color change potential sealers were placed inside the pulp chamber. The cervical access cavity was covered with a thin layer of glass ionomer. After one month, the material was removed, and bleaching was done with 10% carbamide peroxide. The color of the samples was measured by a spectrophotometer before bleaching, one week after bleaching, and one week after bleaching again. The data were subjected to statistical analysis using the Statistical Package for Social Sciences (SPSS) software version 16 (IBM SPSS Statistics, Armonk, NY), with a significance level set at P<0.05. Results The results showed that the factor of time and material used and the opposing effect of these two on the amount of L and ΔE were statistically significant (P<0.05). After one to two weeks of internal bleaching, all groups showed some degree of reduction in sealer-induced discoloration. In addition, in all groups, the largest difference in L was related to the difference in L0 and L2 (before bleaching and one week after bleaching again), and the lowest difference was related to the difference in L0 and L1. Also, the highest ΔE(T0,T1) belonged to the Endofill group, and this significantly differed from the AH26 group. AH26 showed the lowest value of ΔE(T0,T1), and after two weeks, the ΔE of all groups was higher than the clinically observable limit. The highest ΔE(T2,T0) among the groups belonged to the Endofill group. The ΔE(T2,T0) of AH26 and Endofill was significantly higher than AH Plus. Among all ΔE values, the AH Plus group had the lowest values. Conclusion Color change caused by Endofill and AH26 sealers showed a better response to internal bleaching than the AH Plus sealer.

Diagnostic value of long noncoding RNA SNHG15 in gastric cancer: in vitro and in silico studies.

LncRNA SNHG15 has been recognized as the main factor in the progression of various cancer types. However, the underlying mechanisms are not well clarified. This research aimed to explore the diagnostic potential of SNHG15 in gastric cancer (GC) patients and also the effects of SNHG15-miRNA-mRNA network in GC pathobiology. The expression level of SNHG15 in GC tissues and adjacent normal tissues (ANTs) was evaluated by qRT-PCR and also considered in relation to clinicopathologic factors. The ROC curve was explored to consider the specificity and sensitivity of SNHG15. Gene ontology functional annotation and KEGG pathway analysis were performed in order to predict the effects of SNHG15-miRNA-mRNA network in GC pathobiology. SNHG15 was overexpressed in GC tissues compared to ANTs (fold change= 3.87 and P-value = 0.0022). The SNHG15 expression level was not significantly associated with clinicopathologic factors. ROC curve indicated the specificity of 63.51 and sensitivity of 79.73 and the AUC of 0.744 (P-value < 0.0001). Further gene network analysis revealed that SNHG15 interacts with has-miR-613, has-miR-542-3p, and has-miR-1236-3p, and may be involved in the GC pathobiology by affecting the EGFR tyrosine kinase inhibitor resistance, HIF-1 signaling pathway, and VEGF signaling pathway. It can be concluded that SNHG15 may be a diagnostic factor in GC and may contribute in a variety of cancer-related signaling pathways.

Autophagy Inhibition and Sensitization to Cisplatin in Esophageal Cancer Stem-Like Cells via All-trans Retinoic Acid-induced miR-30a.

AIM: Providing insights into the chemoresistance of esophageal squamous cell carcinoma (ESCC) and its dependence on chemotherapy-induced autophagy. BACKGROUND: Autophagy is induced during chemotherapy of cancer cells, promoting resistance to anti-cancer treatments. OBJECTIVE: The objective of this study is to investigate the modulation of microRNA-30a (miR-30a), a known regulator of autophagy, in ESCC cells by all-trans retinoic acid (ATRA). METHODS: Treatment involved ESCC cells KYSE-30 and TE8 with cis-dichloro-diamine platinum (CDDP), enriching CDDP-surviving cells (CDDP-SCs). qRT-PCR and dual luciferase reporter assay (DLRA) were employed to evaluate miR-30a expression and its interaction with Beclin-1 (BECN1) in both CDDP-SCs and those treated with ATRA. RESULTS: Chemotherapy using CDDP led to a significant decrease in miR-30a expression within ESCC cells. Increased autophagy levels were identified in cancer cells exhibiting stem cell-like properties, characterized by the overexpression of specific stem cell markers. These results suggest that the downregulation of miR-30a induced by CDDP treatment may represent a potential underlying mechanism for increased autophagic activity, as evidenced by the upregulation of autophagy-related proteins, such as BECN1 and an elevated LC3-II/LC3-I ratio. ATRA treatment elevated miR-30a expression and disrupted hallmark cancer stem cell (CSC) features in ESCC cells. Further investigations demonstrated that increased miR-30a expression led to a reduction in the expression of its target gene, BECN1, and attenuated BECN1-mediated autophagy. This resulted in an augmentation of CDDP-induced apoptosis in ESCC cells and a G2/M cell cycle arrest. CONCLUSION: CDDP chemotherapy reduced miR-30a, promoting ESCC cell resistance through autophagy and CSC-like features, a process that may be modulated by ATRA.

The evaluation of the possibility of Li-Fraumeni syndrome in cancer patients in East Azarbaijan Province of Iran.

INTRODUCTION: In 1969, Li-Fraumeni syndrome (LFS), which is a rare cancer predisposition syndrome, was reported for the first time. The main problem in LFS is the mutation in the TP53 gene, which is a crucial tumor suppressor gene in the cell cycle. A hereditary syndrome is inherited in an autosomal dominant pattern. There is a significant correlation between this syndrome and various cancers such as sarcoma, breast cancer, brain tumors, and different other types of malignancies. This study aimed to identify the possibility of LFS in cancer patients in the East Azarbaijan, Iran. METHODS: In this experimental study, 45 children with cancer in the Northwest of Iran were investigated for LFS. DNA was extracted from the whole blood cells using the salting-out method. The region within the exons 5-8 of the TP53 gene has been replicated via Polymerase Chain Reaction (PCR) method. The PCR products were sent for Sanger sequencing, and finally, the data were analyzed by Chromas software. RESULTS: In the studied probands, in 12 (26.67%) cases, polymorphisms in Exon 6 and Introns 6 and Intron 7 were identified, and no mutation was observed in exons 5-8 of the TP53 gene. CONCLUSION: Our results show that there were no mutations in exons 5-8 of the TP53 gene as an indication of LFS possibility in these families. Further studies are needed to be done in a bigger population, and Next-Generation Sequencing (NGS) needs to be done to evaluate the whole genome of these patients to complete our data.

Serum Levels of Long Non-coding RNAs NEAT1, GAS5, and GAPLINC Altered in Rheumatoid Arthritis.

BACKGROUND: Rheumatoid arthritis (RA), an autoimmune joint inflammatory disease, presents a significant challenge due to its prevalence, particularly among women, affecting around 6% of individuals over the age of 65. Novel insights into disease mechanisms are crucial for improved diagnostic and therapeutic approaches. OBJECTIVE: Long non-coding RNAs (lncRNAs) have emerged as potential contributors to the pathogenesis of various autoimmune diseases, including RA. This study aims to investigate the unique roles of four lncRNAs-NEAT1, GAS5, TMEVPG1, and GAPLINC-in the etiology of RA. METHODS: Leveraging isolated serum samples from RA patients and healthy controls, we comprehensively evaluated the expression profiles of these lncRNAs. RESULTS: Notably, our findings unveil a distinctive landscape of lncRNA expressions in RA. Among them, GAPLINC exhibited a significantly elevated average expression in the serum samples of RA patients, suggesting a potential biomarker candidate for disease stratification. Importantly, reduced expression of NEAT1 and GAS5 was observed in RA patients, highlighting their possible roles as diagnostic and prognostic markers. Conversely, TMEVPG1 displayed unaltered expression levels in RA samples. CONCLUSION: Our study introduces a novel dimension to RA research by identifying NEAT1, GAS5, and GAPLINC as promising serological biomarkers. These findings hold significant clinical implications, offering potential avenues for improved diagnosis, disease monitoring, and therapeutic interventions in RA.

Polymorphisms and expression levels of TNP2, SYCP3, and AZFa genes in patients with azoospermia.

OBJECTIVE: Azoospermia (the total absence of sperm in the ejaculate) affects approximately 10% of infertile males. Despite diagnostic advances, azoospermia remains the most challenging issue associated with infertility treatment. Our study evaluated transition nuclear protein 2 (TNP2) and synaptonemal complex protein 3 (SYCP3) polymorphisms, azoospermia factor a (AZFa) microdeletion, and gene expression levels in 100 patients with azoospermia. METHODS: We investigated a TNP2 single-nucleotide polymorphism through polymerase chain reaction (PCR) restriction fragment length polymorphism analysis using a particular endonuclease. An allele-specific PCR assay for SYCP3 was performed utilizing two forward primers and a common reverse primer in two PCR reactions. Based on the European Academy of Andrology guidelines, AZFa microdeletions were evaluated by multiplex PCR. TNP2, SYCP3, and the AZFa region main gene (DEAD-box helicase 3 and Y-linked [DDX3Y]) expression levels were assessed via quantitative PCR, and receiver operating characteristic curve analysis was used to determine the diagnostic capability of these genes. RESULTS: The TNP2 genotyping and allelic frequency in infertile males did not differ significantly from fertile volunteers. In participants with azoospermia, the allelic frequency of the SYCP3 mutant allele (C allele) was significantly altered. Deletion of sY84 and sY86 was discovered in patients with azoospermia and oligozoospermia. Moreover, SYCP3 and DDX3Y showed decreased expression levels in the azoospermia group, and they exhibited potential as biomarkers for diagnosing azoospermia (area under the curve, 0.722 and 0.720, respectively). CONCLUSION: These results suggest that reduced SYCP3 and DDX3Y mRNA expression profiles in testicular tissue are associated with a higher likelihood of retrieving spermatozoa in individuals with azoospermia. The homozygous genotype TT of the SYCP3 polymorphism was significantly associated with azoospermia.

Clinical application of circulating tumor DNA in metastatic cancers.

INTRODUCTION: Advances in genomics have facilitated the application of cell-free DNA (cfDNA) and circulating tumor DNA (ctDNA) in phase II and phase III clinical trials. The various mutations of cfDNA/ctDNA have been correlated with clinical features. Advances in next-generation sequencing (NGS) and digital droplet PCR have paved the way for identifying cfDNA/ctDNA mutations. AREAS COVERED: Herein, the biology of ctDNA and its function in clinical application in metastasis, which may lead to improved clinical management of metastatic cancer patients, are comprehensively reviewed. EXPERT OPINION: Metastatic cancer ctDNA shows the greatest frequency of mutations in TP53, HER-2, KRAS, and EGFR genes (alteration frequency of > 50%). Therefore, identifying key mutations frequently present in metastatic cancers can help identify patients with pre-malignant tumors before cancer progression. Studying ctDNA can help determine the prognosis and select appropriate treatments for affected patients. Nevertheless, the obstacles to detecting and analyzing ctDNA should be addressed before translation into routine practice. Also, more clinical trials should be conducted to study the significance of ctDNA in commonly diagnosed malignancies. Given the recent advances in personalized anti-neoplastic treatments, further studies are needed to detect a panel of ctDNA and patient-specific ctDNA for various cancers.

Interferon Signature's Members, a Novel Altered Correlation upon Interferon-ß Treatment in Multiple Sclerosis Patients.

BACKGROUND: Multiple sclerosis (MS) is a chronic inflammatory disease that affects the central nervous system and is characterized by extensive brain damage and neurodegeneration. Immunological, genetic, and histological analyses of MS patients provide data in support of the concept that autoimmunity plays a crucial role in the condition's course. It has been proposed that MS may be treated with interferon (IFN)-ß and other members of the type I family. OBJECTIVE: Low levels of type I IFN in MS patients may affect immunological control, establish the threshold for an IFN therapeutic response, and be"primed" or "fixed" by IFN therapy. METHODS: This study was conducted as a cross-sectional study. qRT-PCR was used to examine the expression of two critical IFN regulatory genes, IFI44 and MX1, in MS patients receiving IFN-ß treatment. RESULTS: The findings demonstrated a considerable rise in the expression of both genes in MS patients treated with IFN-ß compared to those newly diagnosed with the illness. In addition, IFI44 and MX1 might be positively associated with their expression after IFN-ß therapy and be regarded as IFN-ß responsiveness indicators. CONCLUSION: The IFI44/MX1 axis could act as one of the crucial regulators of the disease following IFN-ß treatment.

The effect of glatiramer acetate, IFNß-1a, fingolimod, and dimethyl fumarate on the expression of T-bet, IFN-γ, and MEG3 in PBMC of RRMS patients.

OBJECTIVE: Multiple sclerosis (MS) is a progressing neurodegenerative disease marked by chronic central nervous system inflammation and degeneration.This study investigates gene expression profiles of T-box transcription factor TBX21 (T-bet), interferon-gamma (IFN-γ), and long non-coding RNA MEG3 in peripheral blood mononuclear cells (PBMCs) from treatment-naïve Relapsing-Remitting Multiple Sclerosis patients (RRMS), healthy controls, and RRMS patients on different Disease Modifying Therapies (DMTs). The aim is to understand the role of T-bet, IFN-γ, and MEG3 in MS pathogenesis and their potential as diagnostic and therapeutic targets. RESULTS: Elevated T-bet expression is observed in treatment-naïve RRMS patients compared to healthy individuals. RRMS patients treated with Interferon beta-1alpha (IFNß-1a) and fingolimod exhibit downregulated T-bet and MEG3 expression levels, respectively, with more pronounced effects in females. Healthy individuals show a moderate positive correlation between T-bet and MEG3 and between IFN-γ and T-bet. In RRMS patients treated with Glatiramer Acetate (GA), a strong positive correlation is observed between MEG3 and IFN-γ. Remarkably, RRMS patients treated with Dimethyl Fumarate (DMF) exhibit a significant positive correlation between T-bet and MEG3. These findings underscore the diagnostic potential of T-bet in RRMS, warranting further exploration of MEG3, T-bet, and IFN-γ interplay in RRMS patients.

Gene Polymorphism, Microdeletion, and Gene Expression of PRM1, PRM2, AZFc in Infertile Males.

Background: Background: Male infertility contributes to roughly 15% of all infertility cases in couples. The most common cause of male infertility is azoospermia, which is caused by genetic mutations. The connection between various single nucleotide polymorphisms in the PRM genes and AZF region microdeletions with male infertility has not been reported. Methods: In this case-control study, 100 infertile males (33 with azoospermia, 48 with oligozoospermia, and 19 with severe oligozoospermia) were chosen as the study subjects, and 100 fertile males were selected. Total DNA from peripheral blood was used to amplify two sequence-tagged site markers through multiplex PCR to detect AZFc partial deletions, and SNPs in PRM1 and PRM2 were determined through PCR-RFLP. Furthermore, quantitative real-time PCR was conducted to evaluate PRM1, PRM2, and DAZ1 (found in the AZFc region) expression levels in testis tissue. Results: The frequency of the rs779337774 SNP in the PRM2 gene in the study population had no significant differences. However, a significant association was observed between the rs737008CA genotype (P= 0.013) and the C allele (P= 0.025) as a risk factor for male infant mortality. The deletion of sY254 and sY255 was discovered in azoospermia and severe oligozoospermia patients. Furthermore, all of these genes showed considerably low expression levels. However, only DAZ1 was identified with diagnostic biomarker potential (AUC=0.742). Conclusion: When these genes expression levels are reduced, the likelihood of spermatozoa retrieval in azoospermic individuals is elevated. Furthermore, no significant association was observed between PRM2 polymorphism and azoospermia; however, the CA genotype of PRM1 polymorphism is significantly associated with azoospermia incidence.

Expression Level of lncRNA CYTOR in Iranian Cervical Cancer Patients.

Background: A critical role has been known for lncRNAs in the initiation and development of cancers. Therefore, lncRNAs have been reported as the possible biomarkers in relation to the diagnosis and therapy of malignancies. This project examined the change in CYTOR lncRNA expression in human cervical cancer samples as compared with adjacent healthy ones. Methods: We provided one hundred fifteen pairs of tumorous and adjacent healthy tissue specimens of cervical cancer patients. RNAs were isolated from tissue specimens and cDNAs were synthesized. We considered quantitative Real-time PCR (qRT-PCR) to examine the expression levels of CYTOR lncRNA. In addition, the biomarker activity of CYTOR and the associations between the lncRNA and clinicopathological characteristics were evaluated. Results: The significant increased expression of CYTOR was obtained in cancerous samples as compared with non-cancerous ones (P< 0.0001). A significant correlation was indicated between CYTOR expression and the squamous subtype of cervical cancer (p=0.046). The receiver operating characteristic (ROC) curve-related AUC (area under the curve), specificity, and sensitivity were calculated 0.88, 81.74%, and 80%, respectively, which may introduce CYTOR as a potential biomarker. Conclusion: CYTOR may be an effective oncogene and biomarker in cervical cancer cases given its increased expression in human cervical cancer tissues.

Study of LncRNA BANCR Expression in Tumor Tissues and Adjacent Normal Tissues in Gastric Cancer Patients.

Background: Long non-coding RNAs (lncRNAs) have emerged as crucial regulators in various biological processes, including cancer development and progression. This study aimed to investigate the expression differences of the BRAF-activated non-coding RNA (BANCR) gene in GC tissues compared to adjacent normal tissues. The potential diagnostic significance of BANCR in GC was explored, with the aim of improving diagnostic and therapeutic approaches for this global health burden. Materials and Methods: Tissue samples from 100 gastric cancer (GC) patients were collected, and BANCR expression was analyzed using quantitative real-time PCR. Correlations between BANCR expression and clinicopathological features were assessed, and its biomarker potential was evaluated. Results: In individuals diagnosed with GC, the expression of BANCR was notably elevated in tumor tissues compared to adjacent normal tissues (P < 0.0001). However, the analysis of gene expression data did not demonstrate any statistically significant correlation between elevated BANCR expression and clinicopathological features. According to the ROC analysis, BANCR demonstrated an AUC of 0.6733 (P < 0.0001), with a sensitivity of 73% and a specificity of 45%. However, further evaluation is required to determine its potential as a biomarker (CI 95% = 0.5992 to 0.7473). Conclusions: The observed upregulation of BANCR in GC tissues implies its potential involvement as an oncogenic lncRNA in GC patients. Furthermore, BANCR may serve as a promising biomarker for identification and treatment of GC.