Chronic Administration of Lisdexamfetamine Induces Apoptosis and Inflammation and Reduces Sperm Quality in Adult Male Rats
Abstract
Concerns have been raised about potentially irreversible brain damage and damage to the neuroendocrine system during development when treating attention-deficit/hyperactivity disorder with lisdexamfetamine (LDX), a norepinephrine dopamine reuptake inhibitor. This study aims to elucidate the potential adverse effects of LDX on the male reproductive system due to its widespread use and potential for abuse. In this study, adult male rats were randomized into control and LDX groups. Thirty milligrams per kilogram LDX was administered orally for 3 weeks. After isolation of epididymal spermatozoa, the rats were euthanized and testicular tissues were collected for stereological and molecular analyses. The LDX group showed a decrease in sperm motility and an increase in DNA fragmentation compared to the control group. There was also a dramatic decrease in testosterone in the LDX group. Testicular expression of caspase-3 and TNF-α was significantly increased in the LDX group. According to our findings, prolonged use of LDX leads to reduced sperm quality. It also induces apoptosis, inflammatory response, and pathological changes in the testicular tissue. What we have observed in this study is noteworthy but requires further investigation, particularly in people who use LDX over a longer period of time.
Expression assay of calcium signaling related lncRNAs in autism
Abstract
Background: Calcium signaling has essential roles in the neurodevelopmental processes and pathophysiology of related disorders for instance autism spectrum disorder (ASD). Methods and results: We compared expression of SLC1A1, SLC25A12, RYR2 and ATP2B2, as well as related long non-coding RNAs, namely LINC01231, lnc-SLC25A12, lnc-MTR-1 and LINC00606 in the peripheral blood of patients with ASD with healthy children. Expression of SLC1A1 was lower in ASD samples compared with control samples (Expression ratio (95% CI) 0.24 (0.08-0.77), adjusted P value = 0.01). Contrary, expression of LINC01231 was higher in cases compared with control samples (Expression ratio (95% CI) 25.52 (4.19-154), adjusted P value = 0.0006) and in male cases compared with healthy males (Expression ratio (95% CI) 28.24 (1.91-418), adjusted P value = 0.0009). RYR2 was significantly over-expressed in ASD children compared with control samples (Expression ratio (95% CI) 4.5 (1.16-17.4), adjusted P value = 0.029). Then, we depicted ROC curves for SLC1A1, LINC01231, RYR2 and lnc-SLC25A12 transcripts showing diagnostic power of 0.68, 0.75, 0.67 and 0.59, respectively. Conclusion: To sum up, the current study displays possible role of calcium related genes and lncRNAs in the development of ASD.
Keywords: ATP2B2; Autism spectrum disorder; LINC00606; LINC01231; RYR2; SLC1A1; SLC25A12; lnc-MTR-1; lnc-SLC25A12; lncRNA.
Emerging Role of miRNAs in the Pathogenesis of Periodontitis
Abstract
MicroRNAs (miRNAs) have been found to participate in the pathogenesis of several immune-related conditions through the modulation of the expression of cytokine coding genes and other molecules that affect the activity of the immune system. Periodontitis is an example of these conditions associated with the dysregulation of several miRNAs. Several miRNAs such as let-7 family, miR-125, miR-378, miR-543, miR-302, miR-214, miR-200, miR-146, miR-142, miR-30 and miR-21 have been shown to be dysregulated in patients with periodontitis. miR-146 is the most assessed miRNA in these patients, which is up-regulated in most studies in patients with periodontitis. In the present review, we describe the impact of miRNAs dysregulation on the pathoetiology of periodontitis.
Keywords: MicroRNA; biomarker; diagnose; expression; pathogenesis.; periodontitis.
Link: https://www.eurekaselect.com/article/124570
bstract
Management of Anterior Urethral Stricture: A Survey of Contemporary Practice of Iranian Urologists
Abstract
Purpose: To evaluate Iranian urologists’ approach to urethral stricture and assess how often they select open urethroplasty over minimally invasive procedures.
Keywords: Urethral stricture, Urethroplasty, Urologist, Urethrotomy
Novel blood and tissue-based mitochondrial D-loop mutations detected in an Iranian NAFLD patient cohort
Abstract
Non-alcoholic fatty liver disease (NAFLD) is an increasingly prevalent chronic liver disease characterized by an elusive etiology. In its advanced stages, this condition can pose life-threatening implications. Mitochondrial dysfunction due to its impact on hepatic lipid homeostasis, cytokine release, ROS production, and cell death, contributes to the pathogenesis of NAFLD. Previous research reveals a direct link between NAFLD genetic predictors and mitochondrial dysfunction. The emphasis on the D-loop stems from its association with impaired mtDNA replication, underscoring its crucial role in NAFLD progression. We included 38 Iranian NAFLD patients (comprising 16 patients with non-alcoholic fatty liver [NAFL] and 22 patients with non-alcoholic steatohepatitis [NASH]), with matched blood and liver tissue samples collected from each to compare variations in the mitochondrial D-loop sequence within samples. The mitochondrial DNA (mtDNA) D-loop region was amplified using PCR, and variations were identified through sequencing. The resultant sequences were compared with the reference sequence of human mtDNA available in the MITOMAP Database for comparative analysis. In this study, 97 somatic mutations in the mtDNA D-loop region were identified in NAFLD patients. Our study revealed significant difference between the NAFLD patients and control group in 13 detected mutations (P ≤ 0.05). Novel mutations were discovered in hepatic tissues, while mutation 16220-16221ins C was found in both tissues and blood. A significant difference was found in the distribution of D310 and mt514-mt523 (CA)n repeat variations between NAFLD patients and the control group (P < 0.001). C to T and T to C transitions were the prevalent substitution among patients. Identification of the 16220-16221ins C mutation in both blood and tissue samples from NAFLD patients holds substantial promise as a potential diagnostic marker. However, further research is imperative to corroborate these findings.
Keywords: Biomarker; Diagnosis; Mitochondrial DNA D-Loop; Non-alcoholic fatty liver disease; Single Nucleotide Polymorphism.
Link:https://www.sciencedirect.com/science/article/abs/pii/S1567724924000461?via%3Dihub
Shear Wave Elastography in Assessing Spongiofibrosis of Urethral Stricture: Is It Clinically Useful?
Abstract
Rationale and objectives: To compare urethral stricture shear wave elastography (SWE) with normal areas and assess its association with other explanatory variables.
Keywords: Elasticity imaging techniques; Fibroses; Sonoelastography; Ultrasonography; Urethral stricture.
Link:https://pubmed.ncbi.nlm.nih.gov/38508938/
Human-derived Tumor-On-Chip model to study the heterogeneity of breast cancer tissue
Abstract
One of the leading causes that complicate the treatment of some malignancies, including breast cancer, is tumor heterogeneity. In addition to inter-heterogeneity and intra-heterogeneity of tumors that reflect the differences between cancer cell characteristics, heterogeneity in the tumor microenvironment plays a critical role in tumor progression and could be considered an overlooked and a proper target for the effective selection of therapeutic approaches. Due to the difficulty of completely capturing tumor heterogeneity in conventional detection methods, Tumor-on-Chip (TOC) devices with culturing patient-derived spheroids could be an appropriate alternative. In this research, human-derived spheroids from breast cancer individuals were cultured for 6 days in microfluidic devices. To compare TOC data with conventional detection methods, immunohistochemistry (IHC) and ITRAQ data were employed, and various protein expressions were validated using the transcriptomic databases. The behavior of the spheroids in the collagen matrix and the cell viability were monitored over 6 days of culture. IHC and immunocytochemistry (ICC) results revealed that inter and intra-heterogeneity of tumor spheroids are associated with HER2/ER expression. HER2 expression levels revealed a more important biomarker associated with invasion in the 3D culturing of spheroids. The expression levels of CD163 (as a marker for Ma2 macrophages) and CD44 (a marker for cancer stem cells (CSCs)) were also evaluated. Interestingly, the levels of M2a macrophages and CSCs were higher in triple-negative specimens and samples that showed higher migration and invasion. Cell density and extracellular matrix (ECM) stiffness were also important factors affecting the migration and invasion of the spheroids through the matrix. Among these, rigid ECM revealed a more crucial role than cell density. To sum up, these research findings demonstrated that human-derived spheroids from breast cancer specimens in microfluidic devices provide a dynamic condition for predicting tumor heterogeneity in patients, which can help move the field forward for better and more accurate therapeutic strategies.
Keywords: Breast cancer; Human-derived tumor spheroid; Microfluidics; Tumor heterogeneity; Tumor-On-Chip; Tumor-associated macrophage; cancer stem cell.
Link:https://pubmed.ncbi.nlm.nih.gov/38878646/
Prevalence and clinical significance of incidental findings in chest and abdominopelvic CT scans of trauma patients; A cross-sectional study
Abstract
Background
Imaging may inadvertently reveal pathologies unrelated to their performing purpose, known as incidental findings (IF). This study aimed to assess the prevalence, clinical significance, and documentation of IFs in chest and abdominopelvic computed tomography (CT) scans of trauma patients.
Keywords: Communication; Computed tomography; Emergency imaging; Incidental findings; Multiple trauma; Patient safety; Public health surveillance; Wound and injuries.
Link: https://pubmed.ncbi.nlm.nih.gov/38901332/
Two-Stage Radical Cystoprostatectomy in a Complicated Patient: A Case Report
Abstract
Introduction:
Radical cystectomy plays the main role in the treatment of muscle-invasive and high-grade bladder cancers; however, it still has significant rates of perioperative complications and mortality. The risk of complications is higher in elderly patients with multiple comorbidities. In certain patients, due to simultaneous comorbidities, it becomes challenging to perform long-term orthotopic radical cystectomy surgery.
Keywords: Urinary diversion, Hematuria, Bladder Cancer, Cystectomy
Link: https://brieflands.com/articles/ijcm-146426
Identification of miRNA-Target Gene-Transcription Factor Regulatory Network as Functional Motifs Involved in Glomerular Diabetic Nephropathy
Abstract
The gene regulatory approach based on retrieving information from the database provides a detailed characterization of the molecular mechanisms of disease progression at the level of miRNAs, Transcription Factors (TFs), and genes. Moreover, gene regulatory networks can find an interaction between the miRNAs, TFs, and genes involved in diabetic nephropathy (DN), but the underlying mechanisms of motif remain unclear. We first gathered genes related to glomeruli diabetic nephropathy from GEO and CTD database. Besides, miRNAs targeting genes were collected from the public databases and GEO. Furthermore, regulator TFs were accumulated from related public databases. After that, we explored the regulatory relationships between TF-miRNA, miRNA-Gene, TF-Gene, and miRNA–TF using FANMOD software. Finally, a gene regulatory network consisting of miRNAs, genes, and TFs was constructed, helping the Cytoscape. The global const parameter in FANMOD software used to discover the interaction between miRNAs, genes, TFs, and 3-node regulatory motif types were detected in the resulting network. Among them, it led to the discovery of the two-node feedback motif (2FB) in charge of the up-regulation of miRNA-target gene-TF and TF-mediated cascade motif and co-pointing motif (COP) responsible for the down-regulation of miRNA-target gene–TF. In this study, we found a correlation between miRNAs, TFs, and target genes using a gene regulatory network. We revealed the candidate 3-node motifs associated with the progression of DN. Therefore, detected molecular mechanisms, as well as the relationship between previous studies, demonstrated targets that can help in the discovery of a novel treatment for DN.
Keywords: diabetic nephropathy ,transcription factor , miRNA, motif ,gene regulatory network
Link: https://link.springer.com/article/10.1134/S1022795424700261
TNF-α, and TNFRs in gastrointestinal cancers
Abstract
Tumor necrosis factor-alpha (TNF-α) is a multifunctional cytokine that plays a role in the hemostasis of the immune system, inflammation, and cell proliferation. However, it can also have a dark side as it is involved in pro-inflammatory cytokines and pathological processes such as cell growth and death, autoimmunity, and inflammation, leading to a wide range of chronic inflammatory diseases, including digestive cancer. TNF-alpha binds to two distinct receptors, TNFRI and TNFRII. Upon binding of the ligand to these receptors, TNF receptor-associated factors (TRAFs) are recruited to the cytoplasmic receptor, triggering the activation of transcription factors such as NF-kB and Activator protein 1 (AP_1). In contrast, binding of cytokines to certain family members, such as TNF RI and Fas Ligand (Fas L), leads to the secretion and initiation of apoptosis. Gastrointestinal malignancies are among the most common types of cancer globally. Despite extensive research, the exact cause of these tumors remains a mystery. Unfortunately, they often have a poor prognosis and are often detected at a late stage. The global incidence of gastrointestinal cancers, including those of the stomach, esophagus, colon, liver, and pancreas, is on the rise, leading to a surge in both incidence and mortality. Growth factors and cytokines, which are signaling molecules found in the tumor microenvironment, are thought to be major contributors to the development and metastasis of these cancers. In this review, we explored the role of TNF-α, and its receptors in the development of digestive cancers, including its signaling pathways and functions.
