Differential expression of long non-coding RNAs SRA, HCG22 and MHRT in children with Kawasaki disease

xlomafota13 shared this article with you from Inoreader Differential expression of long non-coding RNAs SRA, HCG22 and MHRT in children with Kawasaki disease Via Experimental and therapeutic medicine Exp Ther Med. 2021 Sep;22(3):1022. doi: 10.3892/etm.2021.10454. Epub 2021 Jul 15. ABSTRACT Kawasaki disease (KD) is an acute, self-limited inflammatory illness during childhood that may lead to thrombosis in the coronary arteries (CA). The major aims of the present study were to estimate the serum levels of long non-coding RNAs (lncRNAs) and the metabolic profiles of patients with KD. A total of 40 specimens were obtained from pediatric patients (40 specimens before and 40 specimens after treatment) who were diagnosed with KD (n=40). The controls comprised healthy children without KD (n=40). The serum levels of lncRNAs steroid receptor RNA activator (SRA), human leukocyte antigen complex group 22 (HCG22) and myosin heavy chain-associated RNA transcript (MHRT) were determined using reverse transcription-quantitative PCR. Subsequently, the correlation between the expression levels of lncRNAs and biochemical parameters of patients was ass essed. Receiver operating characteristic curves were constructed to determine the diagnostic value of the lncRNAs. The results indicated that the serum levels of lncRNAs SRA and HCG22 were higher in patients with acute KD compared with those in healthy controls. B-type natriuretic peptide (BNP) and C-reactive protein were positively correlated with HCG22 in patients with acute KD, while total cholesterol and low-density lipoprotein were negatively correlated with HCG22 in patients with acute KD. The lncRNA MHRT was significantly upregulated in convalescent KD compared with acute KD following intravenous immunoglobulin therapy. In patients with convalescent KD, creatine kinase was positively correlated with MHRT, while BNP and adenosine deaminase were negatively correlated with MHRT. In conclusion, to the best of our knowledge, the present study was the first to identify that the serum levels of lncRNAs SRA and HCG22 in patients with acute KD were higher compared with those in contro l subjects. MHRT levels in patients with convalescent KD were higher than those in the acute phase. LncRNAs SRA and HCG22 may have crucial roles in KD and are potential novel diagnostic biomarkers for KD. LncRNA MHRT may be considered a novel biomarker for predicting the clinical prognosis of patients with KD. PMID:34373708 | PMC:PMC8343885 | DOI:10.3892/etm.2021.104 54 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Subclinical hypothyroidism has no association with insulin resistance indices in adult females: A case-control study

xlomafota13 shared this article with you from Inoreader Subclinical hypothyroidism has no association with insulin resistance indices in adult females: A case-control study Via Experimental and therapeutic medicine Exp Ther Med. 2021 Sep;22(3):1033. doi: 10.3892/etm.2021.10465. Epub 2021 Jul 19. ABSTRACT Longitudinal studies have indicated an association between thyroid function and insulin resistance (IR) or a neutral relationship. Both the lowest tertile of free thyroxine (fT4) and the highest tertile of free triiodothyronine (fT3) were found to be associated with IR in cross-sectional studies. The aim of the present study was to analyze the association between IR and subclinical hypothyroidism in a female adult population from Bucharest, Romania. This is a retrospective pilot case-control study that included female patients examined by two endocrinologists and a diabetologist in an outpatient clinic. The retrospective follow-up had a one-year duration and included the evaluation of thyroid function tests and IR indices based on fasting insulinemia and C-peptide. The study included 176 women, 91 with subclinical hypothyroidism, with a median ag e of 60±17 years and a mean body mass index (BMI) of 27.79±4.76 kg/m2. The majority of the population (50%) was diagnosed with autoimmune thyroiditis, and 17.05% with goitre. The univariate logistic regression using hypothyroidism as the explaining variable found no evidence of a significant relationship between a decreased thyroid function and IR (OR 1.32; P=0.36). Metabolic syndrome was probably the most important determinant of IR in the population group studied. Thus, it was not the thyroid function per se, but the coexistence of other elements of this syndrome that prevailed in determining IR. Advantages to the study are the design that permitted evaluation of IR and the thyroid function at different moments in time as well as the uniformity of the blood tests. The multivariate analyses were adjusted for age, lipid profile and treatment; however, one limiting factor was the absence of other hormonal blood tests. In summary, there was no association between t he thyroid function tests (TSH, fT4) and IR indices in adult Romanian women in a case-control study with one-year retrospective follow-up. PMID:34373719 | PMC:PMC8343699 | DOI:10.3892/etm.2021.10465 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

RNF213 gene silencing upregulates transforming growth factor β1 expression in bone marrow-derived mesenchymal stem cells and is involved in the onset of Moyamoya disease

xlomafota13 shared this article with you from Inoreader RNF213 gene silencing upregulates transforming growth factor β1 expression in bone marrow-derived mesenchymal stem cells and is involved in the onset of Moyamoya disease Via Experimental and therapeutic medicine Exp Ther Med. 2021 Sep;22(3):1024. doi: 10.3892/etm.2021.10456. Epub 2021 Jul 15. ABSTRACT Moyamoya disease (MMD) is a chronic and progressive cerebrovascular occlusion disease, the precise etiology of which is poorly understood. Ring finger protein 213 (RNF213) has been previously identified as a susceptibility gene that serves an important role in angiogenesis, where it has been shown to be closely associated with the onset of MMD. Patients with MMD exhibit increased expression levels of various pro-inflammatory molecules and angiogenic factors. Under certain conditions, bone marrow mesenchymal stem cells (BMSCs) have the ability to differentiate to form neuron-like and microglia-like cells. In the present study, a total of 40 MMD patients and 40 healthy individuals were enrolled. ELISA assays revealed that the expression of serum vascular endothelial growth factor (VEGF) and transforming growth factor β1 (TGF-β1) were higher than that in healthy controls. Furthermore, rat BMSCs (rBMSCs) were isolated and cultured using the whole bone marrow adherence method, which were then phenotyped using flow cytometry. Osteogenic and adipogenic differentiation were determined by using Alizarin red and oil red O staining, respectively. RNF213 was knocked-down using a lentivirus-mediated short hairpin RNA system in passage three rBMSCs, and successful transfection of the RNF213 was confirmed by RT-qPCR and fluorescence imaging. The expression levels of VEGF and TGF-β1 in these rBMSCs were measured on days 7 and 14, respectively. The results demonstrated that RNF213 knockdown upregulated TGF-β1 at both protein and mRNA levels, but did not exert any effect on VEGF gene expression. In conclusion, these findings suggested that that RNF213 knockdown may contribute to aberrant TGF-β1 expression via a pathway that remains to be unidentified, indicating that quantitative changes in RNF213 gene expression may serve an important role in the pathogenesis of MMD. PMID:34373710 | PMC:PMC8343649 | DOI:10.3892/etm.2021.10456 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Multimodal imaging and genetic analysis of adult-onset best vitelliform macular dystrophy in Chinese patients

xlomafota13 shared this article with you from Inoreader Multimodal imaging and genetic analysis of adult-onset best vitelliform macular dystrophy in Chinese patients Via Experimental and therapeutic medicine Exp Ther Med. 2021 Sep;22(3):1034. doi: 10.3892/etm.2021.10466. Epub 2021 Jul 19. ABSTRACT Compared to juvenile-onset best vitelliform macular dystrophy (BVMD), adult-onset BVMD is not well characterized and lacks strict diagnostic criteria. The present study aimed to evaluate the clinical and genetic characteristics of four advanced-age Chinese patients with adult-onset BVMD by combining multimodal imaging and genetic analysis. The four patients (all older than 50 years) were diagnosed with adult-onset BVMD at Zhongshan Ophthalmic Center (Guangzhou, China). Comprehensive ophthalmic examinations were performed, including analyses of best-corrected visual acuity, intraocular pressure, slit-lamp examination, fundus photography, optical coherence tomography, fundus fluorescein angiography and electrooculography. Genomic DNA was extracted from leukocytes isolated from peripheral blood obtained from these patients, their family members and 200 unrelated subjects from the same population. A total of 11 exons of the bestrophin-1 (BEST1) gene were amplified using PCR and sequenced. All of the four patients presented with lesions in the macular area. The patients were diagnosed with adult-onset BVMD based on multimodal imaging and genetic analysis. A total of four recurrent mutations, namely c.763C>T (p.Arg255Trp, p.R255W) in exon 7, c.584C>T (p.Ala195Val, p.A195V) in exon 5, c.910_912del GAT (p.304delAsp, p.D304del) in exon 8 and c.310G>C (p.Asp104His, p.D104H) in exon 4 of BEST1, were identified. Sorting intolerant from tolerant predicted that the amino acid substitutions p.R255W, p.A195V and p.D104H in the BEST1 protein were causing the damage. Combining multimodal imaging and genetic analysis was helpful in confirming the diagnosis of patients with adult-onset BVMD. These results maybe valuable for clinical and genetic counseling and for the development of therapeutic interventions for patients with BVMD. PMID:34373720 | PMC:PMC8343652 | DOI:10.3892/etm.2021.10466 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Carcinomatous-like mastitis due to axillary lymphadenopathy in a case of nasopharyngeal carcinoma: A case report

xlomafota13 shared this article with you from Inoreader Carcinomatous-like mastitis due to axillary lymphadenopathy in a case of nasopharyngeal carcinoma: A case report Via Experimental and therapeutic medicine Exp Ther Med. 2021 Sep;22(3):1026. doi: 10.3892/etm.2021.10458. Epub 2021 Jul 16. ABSTRACT Nasopharyngeal carcinoma (NPC) is a rare form of malignancy, accounting for 2% of all cancers of the head and neck in Europe. Axillary lymph node metastases are very rare in these cases. This is a case report of a 40-year-old premenopausal woman diagnosed in May 2015 with T1N2M0 stage III NPC, treated with induction chemotherapy, followed by chemo-radiotherapy. Post-therapeutic computed tomography (CT) scan showed partial response (PR) on the primary tumor and complete response (CR) on the latero-cervical lymph nodes. In 2017, our patient developed left carcinomatous-like mastitis with axillary lymphadenopathy. This raised suspicions of a carcinomatous mastitis. The pathology report with immunohistochemistry (IHC) of the third biopsy highlighted axillary metastasis of a non-keratinizing squamous cell carcinoma (NSCC). There are very few reference s in the literature regarding axillary metastases from squamous cell carcinoma of the head and neck (HNSCC). As far as we know, this is the first case report of mastitis due to NPC. To conclude, treatment consisted of two surgical excisions of axillary lymphadenopathy associated with local radiotherapy and chemotherapy (neo-adjuvant, adjuvant). The second surgery, performed after radiotherapy, required plastic surgery. A psychiatric evaluation was necessary, revealing a reactive anxiety disorder. This case required multidisciplinary management, where oncology, plastic surgery, pathology and psychiatric specialists collaborated in deciding the therapeutic approach. PMID:34373712 | PMC:PMC8343883 | DOI:10.3892/etm.2021.10458 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Treadmill exercise influences the microRNA profiles in the bone tissues of mice

xlomafota13 shared this article with you from Inoreader Treadmill exercise influences the microRNA profiles in the bone tissues of mice Via Experimental and therapeutic medicine Exp Ther Med. 2021 Sep;22(3):1035. doi: 10.3892/etm.2021.10467. Epub 2021 Jul 19. ABSTRACT As an important regulator involved in cell activity, microRNAs (miRNAs) are important in the process of exercise influencing bone metabolism. The present study aimed to detect and select differentially expressed miRNAs in the bone tissues of mice trained on a treadmill, predict the target genes of these differentially expressed miRNAs and lay a foundation for exploring the effect of treadmill training on bone metabolism through miRNAs. In this experiment, after the mice were trained on a treadmill for 8 weeks, the mechanical properties of mouse femur bone were assessed, and the alkaline phosphatase (ALP) activity and osteocalcin (OCN) protein levels of the bone were assayed. miRNA microarray and reverse transcription-quantitative (RT-q)PCR were performed to select and validate differentially expressed miRNAs in the bone, and the target genes of t hese miRNAs were predicted with bioinformatics methods. In addition, the differentially expressed miRNAs in the bone tissues were compared with those in mechanically strained osteocytes in vitro. Treadmill training improved the mechanical properties of the femur bones of mice, and elevated the ALP activity and OCN protein level in the bone. In addition, 122 differentially expressed miRNAs were detected in the bone, of which nine were validated via RT-qPCR. Among the target genes of these differentially expressed miRNAs, certain candidates were involved in bone metabolism. A total of eight miRNAs were differentially expressed in both bone tissue and osteocytes, exhibiting the same expression trends, and various target genes of these eight miRNAs were also involved in bone metabolism. Treadmill training resulted in altered miRNA expression profiles in the bones of mice (mainly in osteocytes) and the differentially expressed miRNAs may serve important roles in regulating bone me tabolism and osteogenic differentiation. PMID:34373721 | PMC:PMC8343800 | DOI:10.3892/etm.2021.10467 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Palmitic acid up regulates Gal-3 and induces insulin resistance in macrophages by mediating the balance between KLF4 and NF-κB

xlomafota13 shared this article with you from Inoreader Palmitic acid up regulates Gal-3 and induces insulin resistance in macrophages by mediating the balance between KLF4 and NF-κB Via Experimental and therapeutic medicine Exp Ther Med. 2021 Sep;22(3):1028. doi: 10.3892/etm.2021.10460. Epub 2021 Jul 18. ABSTRACT Insulin resistance is the main sign of type 2 diabetes mellitus and is often accompanied by the infiltration of inflammatory factors. These inflammatory factors are mainly produced and secreted by macrophages. The purpose of the current study was to explore the relationship between macrophages and insulin resistance, and to determine its underlying mechanism. The insulin resistance of macrophages was induced by palmitic acid (PA) in vitro. The glucose uptake rate of macrophages, the expression levels of inflammatory cytokines and the expression levels of insulin resistance-related proteins were detected. The protein expression levels of Krüppel-like factor 4 (KLF4), toll-like receptor 4 (TLR4), NF-κB and Galectin-3 (Gal-3) were detected via western blotting and recovery experiments were performed by combining the Gal-3 and TLR4 inhibitor s GB1107 and TAK242. The results revealed that PA-induced macrophages demonstrated insulin resistance. Additionally, KLF4 protein was inhibited and the sugar uptake rate was significantly lower than that of the control group. Western blotting and immunofluorescence assays revealed that the expression of Gal-3 in PA-induced macrophages was significantly upregulated. The addition of the Gal-3 inhibitor GB1107 significantly increased glucose utilization and reduced insulin resistance in PA-treated cells. Inhibitor of TLR4 inhibited the protein expression level of the TLR4/NF-κB pathway. In conclusion, PA promoted the TLR4/phosphorylated-NF-κB signaling pathway by inhibiting KLF4, promoted the upregulation of Gal-3 expression and improved the insulin resistance of macrophages. PMID:34373714 | PMC:PMC8343820 | DOI:10.3892/etm.2021.10460 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

MicroRNA-103a regulates the calcification of vascular smooth muscle cells by targeting runt-related transcription factor 2 in high phosphorus conditions

xlomafota13 shared this article with you from Inoreader MicroRNA-103a regulates the calcification of vascular smooth muscle cells by targeting runt-related transcription factor 2 in high phosphorus conditions Via Experimental and therapeutic medicine Exp Ther Med. 2021 Sep;22(3):1036. doi: 10.3892/etm.2021.10468. Epub 2021 Jul 19. ABSTRACT Vascular calcification, such as atherosclerosis, is a serious complication of chronic kidney disease that is characterized by tunica media calcification, and has gained increasing attention from researchers. The commonly observed association between vascular calcification and osteoporosis suggests a link between bone and vascular disorders. As microRNAs (miRNAs) have a wide range of gene regulation functions, such as cell proliferation, apoptosis, stress and transdifferentiation, the current study aimed to determine whether miRNAs play a vital role in the calcification and osteoblastic differentiation of rat thoracic aorta vascular smooth muscle cells (VSMCs). Gene expression analysis was performed on seven miRNAs (miR-29a, -30b, -103a, -125b, -133a, -143 and -211) that maybe potentially involved in the differentiation of smooth muscle cells into osteoblastic cells. The results showed that the levels of miR-29a, -30b, -103a, -125b and -143 were markedly reduced in the VSMC calcification model, particularly miR-103a, whereas runt-related transcription factor 2 (RUNX2) expression was increased. Furthermore, it was found that the expression of RUNX2 was significantly decreased following the upregulation of miR-103a, and that the expression of RUNX2 was significantly increased by downregulating miR-103a in VSMCs. Therefore, it was concluded that miR-103a plays a notable role in the transdifferentiation of the VSMCs in high phosphorus-induced calcification by targeting the regulation of RUNX2, and may therefore constitute a new target for the diagnosis and treatment of vascular calcification. PMID:34373722 | PMC:PMC8343701 | DOI:10.3892/etm.2021.10468 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Effects of low-dose bufalin combined with hydroxycamptothecin on human castration-resistant prostate cancer xenografts in nude mice

xlomafota13 shared this article with you from Inoreader Effects of low-dose bufalin combined with hydroxycamptothecin on human castration-resistant prostate cancer xenografts in nude mice Via Experimental and therapeutic medicine Exp Ther Med. 2021 Sep;22(3):1015. doi: 10.3892/etm.2021.10447. Epub 2021 Jul 15. ABSTRACT Prostate cancer is the most prevalent tumor found in men worldwide. Despite the efficiency of primary endocrine prostate cancer therapies, more efficient drugs are needed to tackle the most advanced and resistant forms of this condition. The present study investigated the antitumor effects of low-dose bufalin combined with hydroxycamptothecin on castration-resistant prostate cancer (CRPC) in mice, as well as the possible mechanisms of apoptosis induction. CRPC xenograft tumors were generated in mice and, subsequently, mice received appropriate doses of bufalin, hydroxycamptothecin or a combination of the two drugs. Tumors from each treatment group were removed, and the tumor volume, weight and inhibition rate of each group was determined. Hematoxylin and eosin staining was performed for pathological analysis and TUNEL staining was used to assess the level of apoptosis in the xenografts. Immunohistochemistry was used for the analysis of proliferating cell nuclear antigen expression and the expression of Bax, Bcl-XL, p53, programmed cell death 4 (PDCD4), phosphorylated (p)-AKT and glycogen synthase kinase (GSK)-3β was determined by western blotting. Treatment with bufalin significantly (P<0.05) reduced tumor volumes compared with the negative control group, reducing tumor volumes to lower levels when combined with hydroxycampothecin. The combination of bufalin (0.6 or 0.8 mg/kg) and hydroxycampothecin significantly (P<0.05) induced higher levels of cell apoptosis compared with the administration of bufalin or hydroxycampothecin alone. The combination of bufalin and hydroxycampothecin also increased the expression of apoptosis-related proteins Bax, p53, PDCD4 and GSK-3β, and decreased the expression of Bcl-XL and p-AKT compared with a single drug treatment. The present study suggested that the combination of bufalin an d hydroxycampothecin improved the inhibitory effects of both drugs on CRPC tumors in vivo, potentially via the regulation of the PI3K/AKT/GSK-3β and p53-dependent apoptosis signaling pathways. PMID:34373701 | PMC:PMC8343571 | DOI:10.3892/etm.2021.10447 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Repetitive transcranial magnetic stimulation increases neurological function and endogenous neural stem cell migration via the SDF-1α/CXCR4 axis after cerebral infarction in rats

xlomafota13 shared this article with you from Inoreader Repetitive transcranial magnetic stimulation increases neurological function and endogenous neural stem cell migration via the SDF-1α/CXCR4 axis after cerebral infarction in rats Via Experimental and therapeutic medicine Exp Ther Med. 2021 Sep;22(3):1037. doi: 10.3892/etm.2021.10469. Epub 2021 Jul 19. ABSTRACT Neural stem cell (NSC) migration is closely associated with brain development and is reportedly involved during recovery from ischaemic stroke. Chemokine signalling mediated by stromal cell-derived factor 1α (SDF-1α) and its receptor CXC chemokine receptor 4 (CXCR4) has been previously documented to guide the migration of NSCs. Although repetitive transcranial magnetic stimulation (rTMS) can increase neurological function in a rat stroke model, its effects on the migration of NSCs and associated underlying mechanism remain unclear. Therefore, the present study investigated the effects of rTMS on ischaemic stroke following middle cerebral artery occlusion (MCAO). All rats underwent rTMS treatment 24 h after MCAO. Neurological function, using modified Neurological Severity Scores and grip strength test and NSC migration, which were measured using immunofluorescence staining, were analysed at 7 and 14 days after MCAO, before the protein expression levels of the SDF-1α/CXCR4 axis was evaluated using western blot analysis. AMD3100, a CXCR4 inhibitor, was used to assess the effects of SDF-1α/CXCR4 signalling. In addition, neuronal survival was investigated using Nissl staining at 14 days after MCAO. It was revealed that rTMS increased the neurological recovery of rats with MCAO, facilitated the migration of NSC, augmented the expression levels of the SDF-1α/CXCR4 axis and decreased neuronal loss. Furthermore, the rTMS-induced positive responses were significantly abolished by AMD3100. Overall, these results indicated that rTMS conferred therapeutic neuroprotective properties, which can restore neurological function after ischaemic stroke, in a manner that may be associated with the activation of the SDF-1α/CXCR4 axis. PMID:34373723 | PMC:PMC8343462 | DOI:10.3892/etm.2021.10469 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.