Comprehensive bioinformatics analysis of key miRNAs and signaling pathways in the body fluids of human knee osteoarthritis.

Osteoarthritis (OA) is one of the principal causes of chronic joint disease with a series of pathological features. The present study aimed to identify key microRNAs (miRNAs) and signaling pathways in OA biological fluids to explain the potential mechanisms underlying the disease and introduce OA biomarkers using computational analysis. Differentially expressed microRNAs (DEmiRNAs) in the serum, plasma, and synovial fluids of OA patients were identified using the GEO2R, limma, and DESeq2 packages in the R software based on the dataset from GSE151341, GSE105027, and GSE126677. The gene ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG), and network construction analyses were performed for overlapping DEmiRNAs. Forty DEmiRNAs overlapped in the plasma, serum, and synovial fluids of OA patients. The expression patterns of the DEmiRNAs in the serum and plasma were almost the same, while they were reversed in the synovial fluid. Differentially expressed hsa-miR-146a-5p and hsa-miR-335-5p miRNAs showed downregulation in all 3 OA sample types. According to enrichment analysis regarding OA pathogenesis, the signaling pathways of TGF-ß, Hippo, FoxO, PI3K-Akt, and mTOR were significant, with hsa-miR-146a-5p and hsa-miR-335-5p involved in their regulation. The present informatics study for the first time provides insights into the potential diagnostic targets of OA by analyzing overlapping miRNAs and their relevant signaling pathways in human knee fluids (serum, plasma, and synovial fluids).

Concurrent ulnar plastic deformity and ipsilateral humeral condylar fracture: A case report.

INTRODUCTION AND IMPORTANCE: Plastic deformities usually occur in skeletally immature bones not completely ossified due to longitudinal forces on their distal ends, especially the forearm and lower legs. Pediatric lateral humeral condylar fractures (LHCFs) constitute the second most common intra-articular fracture in the upper extremity. Nevertheless, plastic deformities accompanied by other traumatic injuries, including LHCFs, are atypical and rare. This study presents an exceedingly rare case of the concurrence of a plastic deformity and an ipsilateral fracture of the lateral condyle of the humerus in a 6-year-old Persian boy. CASE PRESENTATION: The 6-year-old Persian injured boy referred to orthopedic clinic with an obvious deformity in the right upper limb with a limited motion range in the ipsilateral elbow. The patient underwent open-fixation surgery for LHCF fixation and suitable maneuvers to rectify the ulnar plastic deformity. Our findings indicated an acceptable outcome for this approach. His injured limb was reformed without deformities, and the complete union of the fractured area was accomplished eight weeks after surgery. CLINICAL DISCUSSION: The case is remarkable as reminding that we have to care concomitant "minor" injuries to the main fracture and to correctly treat them. Furthermore, open fixation surgery for LHCF rectification before fixing the ulnar deformity with the aid of a suitable maneuver led to good outcome and acceptable rehabilitation in a case of concurrent ulnar plastic deformity and an ipsilateral fracture of the external condyle of the humerus. CONCLUSION: Our approach helps to avoid further tissue damage and prevent the 2-stage surgical process.

Significance of microRNA-targeted ErbB signaling pathway genes in cardiomyocyte differentiation.

OBJECTIVE(S): Cardiomyocyte differentiation is a complex process that follows the progression of gene expression alterations. The ErbB signaling pathway is necessary for various stages of cardiac development. We aimed to identify potential microRNAs targeting the ErbB signaling pathway genes by in silico approaches. METHODS: Small RNA-sequencing data were obtained from GSE108021 for cardiomyocyte differentiation. Differentially expressed miRNAs were acquired via the DESeq2 package. Signaling pathways and gene ontology processes for the identified miRNAs were determined and the targeted genes of those miRNAs affecting the ErbB signaling pathway were determined. RESULTS: Results revealed highly differentially expressed miRNAs were common between the differentiation stages and they targeted the genes involved in the ErbB signaling pathway as follows: let-7g-5p targets both CDKN1A and NRAS, while let-7c-5p and let-7d-5p hit CDKN1A and NRAS exclusively. let-7 family members targeted MAPK8 and ABL2. GSK3B was targeted by miR-199a-5p and miR-214-3p, and ERBB4 was targeted by miR-199b-3p and miR-653-5p. miR-214-3p, miR-199b-3p, miR-1277-5p, miR-21-5p, and miR-21-3p targeted CBL, mTOR, Jun, JNKK, and GRB1, respectively. MAPK8 was targeted by miR-214-3p, and ABL2 was targeted by miR-125b-5p and miR-1277-5p, too. CONCLUSION: We determined miRNAs and their target genes in the ErbB signaling pathway in cardiomyocyte development and consequently heart pathophysiology progression.

Differential Expression of lincRNA-ROR Spliced Transcript Variants in Breast Cancer.

Background: We investigated the expression pattern of a human stem cell-specific, large intergenic noncoding RNA (lincRNA) regulator of reprogramming (lincRNA-ROR) and its spliced transcript variants in breast tumors. Breast cancer is the leading cause of cancer mortality in women; therefore, finding a reliable diagnostic tumor marker, based on the molecular profile of tumor cells, is warranted. Methods: qRT-PCR was used to investigate the expression alteration of a specific stem cell-related lincRNA and its spliced transcript variants in breast tumors which provided by the Iran National Tumor Bank (2014-2016). Suitability of lincRNA-ROR and expression alterations of its spliced transcript variants as breast tumor biomarkers were examined by ROC curve analysis. Results: Expression was significantly upregulated in lincRNA-ROR variants 1 (NR-048536) and 4 (AB844432) and downregulated in variant 3 (AB844431), with expression levels failing to distinguish between breast tumor types, grades, and malignancy stages. Whereas ROC curve analysis gave good scores to the expressions of variants 1 (AUC=0.7675, P=0.003) and 3 (AUC=0.9383, P=0.00173), suggesting their suitability as potential breast tumor biomarkers, it gave an AUC score of 0.6033 for lincRNA-ROR spliced variant 4 (P=0.4118), denoting its unsuitability as a breast cancer biomarker. Conclusion: Aberrant expressions of lincRNA-ROR spliced transcript variants could serve as reliable biomarkers with potential usefulness in breast cancer diagnosis. However, further research should elucidate the role and tissue expression of lincRNA-ROR spliced transcript variants in various cancers.

From traditional medicine to modern oncology: Scutellarin, a promising natural compound in cancer treatment.

Natural substances are increasingly being used as cancer treatments. Scutellarin, as a flavonoid, recently has been identified in a Chinese herbal extract called Erigeron breviscapus (Vant.). Scutellarin is being researched for its potential benefits due to the discovery that it possesses a variety of biological effects, such as neuroprotective, anti-bacterial, and anti-viral properties. In addition to these biological functions, scutellarin has also been found to have anti-tumor properties. The underlying mechanisms of scutellarin's anticancer activity involve its ability to inhibit various signaling pathways, such as Jak/STAT, ERK/AMPK, and Wnt/ß-catenin. Additionally, scutellarin activates intrinsic and extrinsic apoptotic pathways, which causes the death of tumor cells, interrupts the cell cycle, and promotes its arrest. By limiting metastasis, angiogenesis, drug resistance, and other tumorigenic processes, scutellarin also reduces the aggressiveness of tumors. Despite its promising anticancer activity, scutellarin faces several challenges in its clinical development, including poor solubility, bioavailability, and pharmacokinetic properties. Therefore, it has been suggested that certain modifications can enhance the pharmacogenetic capabilities of scutellarin to decrease its limited water solubility. In conclusion, scutellarin represents a potential candidate for cancer treatment and further studies are needed to explore its clinical utility and optimize its therapeutic potential.

Distinct gene expression patterns of SOX2 and SOX2OT variants in different types of brain tumours.

Numerous investigations have been recently published on the dysregulated expression of long-noncoding RNAs (lncRNAs) in various cancer types, emphasizing that abnormal lncRNA expression is a major contributor to tumourigenesis. A broad spectrum of lncRNAs is expressed in the central nervous system, where these RNAs seem to play key roles in brain development and function. In addition to expressing SOX2, a master regulator of pluripotency that lies within its third intron, lncRNA SOX2OT has a proposed role in regulating neural development. Based on our previous studies, alternative splicing of SOX2OT generates two alternatively spliced variants (SOX2OT-S1 and SOX2OT-S2). The present study investigated the expression patterns of SOX2OT variants and SOX2 in three principal types of brain tumours (gliomas, meningiomas and pituitary adenomas) and in four brain tumour cell lines (U87-MG, 1321N1, A172 and DAOY). Total RNAwas extracted from 34 human brain tumour specimens, and the expression profile of target genes was measured using a real-time reverse transcription PCR approach. Our data revealed distinct expression patterns for SOX2OT variants and SOX2 in the brain tumour samples, indicating their potential involvement in brain tumourigenesis. Moreover, our results highlighted the potential usefulness of SOX2OT-S1, SOX2OT-S2, and SOX2 in molecular diagnosis and brain tumour classification.

Pathophysiology, Diagnosis, Treatment, and Genetics of Carpal Tunnel Syndrome: A Review.

Carpal tunnel syndrome (CTS) is a common peripheral canalicular nerve entrapment syndrome in the upper extremities. The compression of or injury to the median nerve at the wrist as it passes through a space-limited osteofibrous carpal canal can cause CTS, resulting in hand pain and impaired function. The present paper reviews the literature on the prevalence, pathology, diagnosis, treatment, and risk factors of CTS in conjunction with the role of genetic factors in CTS etiology. CTS diagnosis is primarily linked with clinical symptoms; still, it is simplified by sophisticated approaches such as magnetic resonance imaging and ultrasonography. CTS symptoms can be ameliorated through conservative and surgical strategies. The exact CTS pathophysiology needs clarification. Genetic predispositions to CTS are augmented by various variants within genes; however, CTS etiology could include risk factors such as wrist movements, injury, and specific conditions (e.g., age, body mass index, sex, and cardiovascular conditions). The high prevalence of CTS diminishes the quality of life of its sufferers and imposes costs on health systems, hence the significance of research and clinical trials to elucidate CTS pathogenesis and develop novel therapeutic targets.

CD19, ALDH18A1, and CACNA1G as Significant Hub Genes in End-Stage Osteoarthritis.

Background: Osteoarthritis is one of the principal causes of chronic joint disease and may progressively engender disability in elderly individuals. The present study aimed to identify differentially expressed genes and associated signaling pathways in end-stage osteoarthritis. Methods: Differentially expressed messenger RNAs in the early and end stages of osteoarthritis were examined through gene expression omnibus 2R (GEO2R) in the GSE32317 dataset. Subsequently, gene ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG), and protein-protein interaction (PPI) analyses were conducted. Furthermore, microRNAs targeting hub genes were investigated using the miRcode database. This study was conducted jointly at Bam University of Medical Sciences and Rajaie Cardiovascular, Medical and Research Center on October 2022. Results: Differentially expressed data demonstrated downregulation in 134 genes and upregulation in 189 genes in end-stage knee osteoarthritis. The results of the enrichment and PPI analyses determined 4 end-stage knee osteoarthritis-related hub genes: IL-1B, CD19, CACNA1G, and ALDH18A1. The knee osteoarthritis-related key genes were involved in the Wnt signaling, B cell receptor signaling, calcium signaling, circadian entrainment, arginine and proline metabolism, axon guidance, and cytokine-cytokine receptor pathways. Additionally, the microRNAs targeting the 4 aforementioned genes were predicted. Conclusion: The present study is the first to provide fresh insights into the potential therapeutic targets of key genes, namely CD19, CACNA1G, and ALDH18A1, differentially expressed in end-stage osteoarthritis and their relevant signaling pathways and interactive microRNAs.

Circular RNAs: New Players in Cardiomyopathy.

Cardiomyopathies comprise a heterogeneous group of cardiac diseases identified by myocardium disorders and diminished cardiac function. They often lead to heart failure or heart transplantation and constitute one of the principal causes of morbidity and mortality worldwide. Circular RNAs (circRNAs) are a novel type of noncoding RNAs. They are covalently closed and single-stranded and derived from the exons and introns of genes by alternative splicing. This specific structure renders them resistant to exonuclease digestion. Many recent studies have demonstrated that circRNAs are highly abundant and conserved and can play central roles in biological functions such as microRNA (miRNA) sponging, splicing, and transcription regulation. Emerging evidence indicates that circRNAs can play significant roles in cardiovascular diseases, including cardiomyopathies. In this review, we briefly describe the current understanding regarding the classification, nomenclature, characteristics, and function of circRNAs and report recent significant findings concerning the roles of circRNAs in cardiomyopathies. Furthermore, we discuss the clinical application potential of circRNAs as the therapeutic targets and diagnostic biomarkers of cardiomyopathies.

Tenascin-C as a noninvasive biomarker of coronary artery disease.

BACKGROUND: Coronary artery disease (CAD), is the leading cause of mortality and morbidity worldwide. Tenascin-C (TNC) with high expression levels in inflammatory and cardiovascular diseases, leads to the rupture of atherosclerotic plaques. The origin of plaque destabilization can be associated to endothelial dysfunction. Given the high prevalence of CAD, finding valuable biomarkers for its early detection is of great interest. Using serum samples from patients with CAD and individuals without CAD, we assessed the efficacy of TNC expression levels in serum exosomes and during endothelial cell differentiation as a noninvasive biomarker of CAD. METHODS: TNC expression was analyzed using the RNA-sequencing data sets of 6 CAD and 6 normal samples of blood exosomes and endothelial differentiation transitions. Additionally, TNC expression was investigated in the serum samples of patients with CAD and individuals without CAD via qRT-PCR. ROC curve analysis was employed to test the suitability of TNC expression alterations as a CAD biomarker. RESULTS: TNC exhibited higher expression in the exosomes of the CAD samples than in those of the non-CAD samples. During endothelial differentiation, TNC expression was upregulated and then consistently downregulated in mature endothelial cells. Moreover, TNC was significantly upregulated in the serum of the CAD group (P = 0.02), with an AUC of 0.744 for the expression level (95% confidence interval, 0.582 to 0.907; P = 0.011). Hence its expression level can be discriminated CAD from non-CAD samples. DISCUSSION: Our study is the first to confirm that altered TNC expression is associated with pathological CAD conditions in Iranian patients. The expression of TNC is involved in endothelial differentiation and CAD development. Accordingly, TNC can serve as a valuable noninvasive biomarker with potential application in CAD diagnosis.

Traumatic Cervical Vertical Translational Injury: A Case Report.

Traumatic cervical translational injury is a notably rare and highly unstable subtype of type C sub-axial cervical spine injury with high morbidity and mortality rates. Hereby, we report a 41-years-old man who was a case of multiple trauma due to car rollover. He was completely conscious, complaining of cervical pain, with a GCS score of 15/15. His neurological examination was unremarkable. The cervical CT scan revealed a vertical translation at the C6-C7 level (roughly 11 mm) and bilateral facet joint diastases which are highly unstable injuries. A two-stage combined anterior and posterior fixation operation was performed. First, an anterior cervical discectomy and fusion with autologous graft and plate fixation, and then a posterior approach with lateral mass screw fixation was performed. Disruption of the anterior longitudinal ligament, annulus fibrosis, facet capsules, and severe strain of ligamentum flavum was noted intraoperatively. He had no early and late complications within 2 years of follow-up.

The Role of Atypical Chemokine Receptor D6 (ACKR2) in Physiological and Pathological Conditions; Friend, Foe, or Both?

Chemokines exert crucial roles in inducing immune responses through ligation to their canonical receptors. Besides these receptors, there are other atypical chemokine receptors (ACKR1-4) that can bind to a wide range of chemokines and carry out various functions in the body. ACKR2, due to its ability to bind various CC chemokines, has attracted much attention during the past few years. ACKR2 has been shown to be expressed in different cells, including trophoblasts, myeloid cells, and especially lymphoid endothelial cells. In terms of molecular functions, ACKR2 scavenges various inflammatory chemokines and affects inflammatory microenvironments. In the period of pregnancy and fetal development, ACKR2 plays a pivotal role in maintaining the fetus from inflammatory reactions and inhibiting subsequent abortion. In adults, ACKR2 is thought to be a resolving agent in the body because it scavenges chemokines. This leads to the alleviation of inflammation in different situations, including cardiovascular diseases, autoimmune diseases, neurological disorders, and infections. In cancer, ACKR2 exerts conflicting roles, either tumor-promoting or tumor-suppressing. On the one hand, ACKR2 inhibits the recruitment of tumor-promoting cells and suppresses tumor-promoting inflammation to blockade inflammatory responses that are favorable for tumor growth. In contrast, scavenging chemokines in the tumor microenvironment might lead to disruption in NK cell recruitment to the tumor microenvironment. Other than its involvement in diseases, analyzing the expression of ACKR2 in body fluids and tissues can be used as a biomarker for diseases. In conclusion, this review study has tried to shed more light on the various effects of ACKR2 on different inflammatory conditions.

hsa-miR-508-5p as a New Potential Player in Intervertebral Disc Degeneration.

Intervertebral disc degeneration (IDD) is widely known as the principal cause of low back pain, diminishing patients' quality of life and imposing a huge economic burden on healthcare systems worldwide. However, the underlying mechanisms of IDD remain to be determined. This study aimed to scrutinize data sets via bioinformatics to identify microRNAs (miRNAs)/genes and pathways associated with IDD. The array profiling of patients with IDD and individuals without IDD was acquired from the Gene Expression Omnibus (GEO) database (viz., GSE19943, GSE63492, and GSE34095). The expression profiles of miRNAs and genes with differential patterns were analyzed using GEO2R. The target genes of the chosen miRNA were then examined, and in silico functional analyses were performed on the signaling pathways and biological processes of the differentially expressed genes. Three human miRNAs were up and downregulated in IDD patients in the examined data sets. Among them, hsa-miR-508-5p had a significant differential expression in the IDD group, and SEC11A, IPO5, FN1, and MRPS10, as the targets of hsa-miR-508-5p, were upregulated in the IDD group. Furthermore, extracellular matrix-receptor interactions, focal adhesion, and actin cytoskeleton regulation were important pathways involved in IDD. Our analysis identified hsa-miR-508-5p as a novel miRNA involved in IDD pathogenies. Our findings not only further confirmed the significant role of miRNAs in IDD pathogenesis but also extended the spectrum of the miRNAs and genes involved in IDD. Though, still, further experimental investigations are needed to confirm our findings.

Iatrogenic L5 Nerve Injury Following Decortication of the Sacral Ala in Posterolateral Lumbosacral Fusion Surgery.

STUDY DESIGN: Cadaver study. OBJECTIVES: To investigate the risk of the L5 nerve injury following sacral ala decortication performed during lumbosacral posterolateral fusion surgery. METHODS: Fourteen fresh cadaver pelvises were dissected through an anterior approach and the L5 nerves on both sides were explored and macroscopically examined by direct observation. Then, the corticotomy of the sacral ala was performed at 0°, 20°, and 30° angles to the sagittal plane through the posterior approach. The site of sacral ala decortication was checked on each side and its distance to the L5 nerve root was measured. RESULTS: The tip of the osteotome was in the danger zone (5 mm medial to 5 mm lateral to the L5 nerve) in all cases (100%) where the osteotome had 0° angle to the sagittal plane. For those with a 20° angle, the osteotome tip laid in the danger zone in 83% and intermediate zone (between 6 to 15 mm lateral to the nerve) in 17% of cases. For those with a 30° angle, the tip was in the safe zone (>15 mm lateral to the nerve) in all cases (100%). CONCLUSION: Osteotomy of the sacral ala with <30° angle to the sagittal plane risks injury to the L5 nerve; whereas osteotomy angle >30° would not cause any injury to the nerve. It should be considered as a possible cause of iatrogenic L5 nerve injury in patients undergoing posterolateral lumbosacral fusion.

Development of the DNA-based voltammetric biosensor for detection of vincristine as anticancer drug.

In the article presented herein, a deoxyribonucleic acid (DNA) biosensor is introduced for Vincristine determination in pharmaceutical preparations based on the modification of screen printed electrode (SPE) with double-stranded DNA (ds-DNA), polypyrrole (PP), peony-like CuO:Tb3+ nanostructure (P-L CuO:Tb3+ NS). The developed sensor indicated a wide linear response to Vincristine concentration ranged from 1.0 nM to 400.0 µM with a limit of detection as low as .21 nM. The intercalation of Vincristine with DNA guanine led to the response. The optimized parameters for the biosensor performance were ds-DNA/Vincristine interaction time, DNA concentration and type of buffer solution. The docking investigation confirm the minor groove interaction between guanine base at surface of or ds-DNA/PP/P-L CuO:Tb3+ NS/SPE and Vincristine. The proposed sensor could successfully determine Vincristine in Vincristine injections and biological fluids, with acceptable obtains.