Long non-coding RNA RP11-84C13.1 promotes osteogenic differentiation of bone mesenchymal stem cells and alleviates osteoporosis progression via the miR-23b-3p/RUNX2 axis

xlomafota13 shared this article with you from Inoreader Long non-coding RNA RP11-84C13.1 promotes osteogenic differentiation of bone mesenchymal stem cells and alleviates osteoporosis progression via the miR-23b-3p/RUNX2 axis Via Experimental and therapeutic medicine Exp Ther Med. 2021 Nov;22(5):1340. doi: 10.3892/etm.2021.10775. Epub 2021 Sep 22. ABSTRACT The objective of the present study was to determine the role of RP11-84C13.1 in osteoporosis (OP) and its molecular mechanism. First, clinical samples were collected from OP patients and normal control patients. Human bone marrow stromal cells (hBMSCs) were extracted from femoral head tissues. Runt-related transcription factor 2 (RUNX2) and RP11-84C13.1 serum levels were assessed by reverse transcription-quantitative (RT-q)PCR. Following transfection of pcDNA-RP11-84C13.1, si-RP11-84C13.1, microRNA (miRNA)-23b-3p mimic and miRNA-23b-3p inhibitor, the expression levels of RUNX2 and RP11-84C13.1 were determined by RT-qPCR. In addition, the osteogenic ability of hBMSCs was assessed by Alizarin Red staining. The binding of RP11-84C13.1 to miRNA-23b-3p and the binding of miRNA-23b-3p to RUNX2 was confirmed by dual-luciferase reporter gene assay. Long non-coding RNA (lncRNA) RP11-84C13.1 was significantly downregulated in the serum of OP patients. The osteogenic differentiation-related genes RUNX2 and RP11-84C13.1 were markedly upregulated in a time-dependent manner, while the miRNA-23b-3p level gradually decreased in hBMSCs with the prolongation of osteogenesis. RP11-84C13.1 knockdown inhibited the osteogenic differentiation of hBMSCs. Furthermore, RP11-84C13.1 regulated RUNX2 expression by targeting miRNA-23b-3p. Overexpression of miRNA-23b-3p partially reversed the promoting effect of RP11-84C13.1 on the osteogenesis of hBMSCs. In conclusion, lncRNA RP11-84C13.1 upregulated RUNX2 by absorbing miRNA-23b-3p, and thus induced hBMSC osteogenesis to alleviate osteoporosis. PMID: 34630694 | PMC:PMC8495569 | DOI:10.3892/etm.2021.10775 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

miR-638 suppresses proliferation by negatively regulating high mobility group A1 in ovarian cancer cells

xlomafota13 shared this article with you from Inoreader miR-638 suppresses proliferation by negatively regulating high mobility group A1 in ovarian cancer cells Via Experimental and therapeutic medicine Exp Ther Med. 2021 Nov;22(5):1319. doi: 10.3892/etm.2021.10754. Epub 2021 Sep 20. ABSTRACT Ovarian cancer is one of the most common gynecological diseases with high mortality rates. Previous studies have shown that microRNA (miR)-638 is associated with tumorigenesis. The present study aimed to assess the role and underlying mechanisms of miR-638 in ovarian cancer. miR-638 expression was detected in ovarian cancer tissues and miR-638 was overexpressed or knocked down in ovarian cancer OVCAR-3 and Caov-3 cells. The clinical results revealed that miR-638 expression was downregulated in ovarian cancer tissues compared with in adjacent normal tissues. miR-638 expression was also found to be relatively low in OVCAR-3 cells whilst being relatively high in Caov-3 cells among the five ovarian cancer cell lines tested. miR-638 overexpression inhibited cell viability, arrested the cell cycle at the G1 phase and promoted apoptosis in OV CAR-3 cells. By contrast, miR-638 knockdown increased Caov-3 cell viability, facilitated cell cycle progression and inhibited apoptosis. miR-638 reduced the expression of high mobility group A1 (HMGA1) by directly targeting its 3' untranslated region. HMGA1 overexpression reversed the inhibition of proliferation induced by miR-638 overexpression in OVCAR-3 cells. These results suggest that miR-638 may serve to be a suppressor of ovarian cancer by regulating HMGA1, which may provide a potential therapeutic target for ovarian cancer. PMID:34630673 | PMC:PMC8495545 | DOI:10.3892/etm.2021.10754 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Blood glucose control contributes to protein stability of Ski-related novel protein N in a rat model of diabetes

xlomafota13 shared this article with you from Inoreader Blood glucose control contributes to protein stability of Ski-related novel protein N in a rat model of diabetes Via Experimental and therapeutic medicine Exp Ther Med. 2021 Nov;22(5):1341. doi: 10.3892/etm.2021.10776. Epub 2021 Sep 22. ABSTRACT Ski-related novel protein N (SnoN) negatively regulates the transforming growth factor-β1 (TGF-β1)/Smads signaling pathway and is present at a low level during diabetic nephropathy (DN), but its underlying regulatory mechanism is currently unknown. The present study aimed to assess the effects of insulin-controlled blood glucose on renal SnoN expression and fibrosis in rats with diabetes mellitus (DM). Streptozotocin-induced DM rats were treated with insulin glargine (INS group) following successful model establishment. Blood samples were collected and centrifuged for biochemical indexes and the kidneys were collected for morphological analysis. In vitro, rat renal proximal tubular epithelial cells were treated with high-glucose medium for 24 h and transferred to normal glucose medium for 24 h. The expression levels of TGF-β1, SnoN, Sma d ubiquitin regulatory factor 2 (Smurf2), Arkadia, Smads, E-cadherin, α-smooth muscle actin and collagen III were assessed by western blotting and immunohistochemistry. The ubiquitylation of SnoN was detected by immunoprecipitation, and the expression levels of SnoN mRNA were evaluated by reverse transcription-quantitative PCR. The biochemical parameters and morphology indicated that renal fibrosis was notable in the DM group and mitigated in the INS group. Compared with the control group, TGF-β1, phosphor (p)-Smad2, p-Smad3, Smurf2 and Arkadia levels were enhanced in the DM group, and the levels of SnoN protein were decreased, whereas the levels of SnoN mRNA and ubiquitylation were increased in renal tissues. Notably, treatment with insulin reversed this trend. Furthermore, changing the glucose levels in the medium from high to normal glucose suppressed the epithelial-mesenchymal transition of NRK-52E cells by restoring the SnoN protein levels, and this phenomenon was impaired by the knockout of SnoN. SnoN protein levels were likely reduced through a mechanism enhanced by the ubiquitin proteasome system, which reversed the transcriptional activation of SnoN during DN progression. In addition, controlling blood glucose may delay DN fibrosis by rescuing the protein stability of SnoN. PMID:34630695 | PMC:PMC8495591 | DOI:10.3892/etm.2021.10776< /a> View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

MEX3A knockdown inhibits the tumorigenesis of colorectal cancer via modulating CDK2 expression

xlomafota13 shared this article with you from Inoreader MEX3A knockdown inhibits the tumorigenesis of colorectal cancer via modulating CDK2 expression Via Experimental and therapeutic medicine Exp Ther Med. 2021 Nov;22(5):1343. doi: 10.3892/etm.2021.10778. Epub 2021 Sep 22. ABSTRACT Colorectal cancer (CRC) is a malignant tumor of the gastrointestinal tract and a leading cause of cancer-associated mortality worldwide. Mex-3 RNA binding family member A (MEX3A) promotes the progression of multiple types of cancer, including ovarian and cervical cancer. However, to the best of our knowledge, the role of MEX3A in CRC is not completely understood. Therefore, the present study aimed to investigate the function of MEX3A in CRC. The mRNA and protein expression levels of MEX3A in CRC cells were analyzed using reverse transcription-quantitative PCR and western blotting, respectively. Cell Counting Kit-8 assays were used to measure cell viability. Cell apoptosis and cell cycle distribution were detected via flow cytometry, and CRC cell invasion was analyzed by performing Transwell assays. Moreover, the mitochondrial membrane potential i n CRC cells was measured via JC-1 staining. The results of the present study revealed that the expression levels of MEX3A were upregulated in CRC tissues compared with adjacent healthy tissues. MEX3A knockdown notably inhibited CRC cell viability, and induced apoptosis and mitochondrial injury. In addition, MEX3A knockdown markedly induced G1 phase cell cycle arrest in CRC cells via downregulating CDK2 expression. In conclusion, the findings of the present study suggested that MEX3A knockdown may inhibit the tumorigenesis of CRC cells by regulating CDK2 expression. Therefore, MEX3A may serve as a novel target for CRC treatment. PMID:34630697 | PMC:PMC8495542 | DOI:10.3892/etm.2021.10778 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Dermatological and endocrine elements in Carney complex (Review)

xlomafota13 shared this article with you from Inoreader Dermatological and endocrine elements in Carney complex (Review) Via Experimental and therapeutic medicine Exp Ther Med. 2021 Nov;22(5):1313. doi: 10.3892/etm.2021.10748. Epub 2021 Sep 17. ABSTRACT Carney complex (CΝC) is a very rare, autosomal dominant, hereditary syndrome. Seventy percent of individuals with CNC have germline inactivating or deleting mutations of the CNC1 gene [currently known as protein kinase cAMP-dependent type I regulatory subunit α (PRKAR1A), located at the 17q22-24 chromosome level], with 30% of cases presenting with phosphodiesterase gene mutations. A member of the lentiginosis family, dermatological features include: skin pigmentation, cutaneous/mucosal myxomas, usually diagnosed by the age of 20 years (neonatal presentation is exceptional, requiring a meticulous differential diagnosis). Melanocyte-derived tumors such as epithelioid blue nevi (with different levels of pigmentation) and pigmented epithelioid melanocytoma (previously 'animal-type melanoma') are often found. Myxomas, mesenchymal tumor s with mostly a benign pattern, may be recurrent. Primary cutaneous melanotic schwannoma are atypical, while non-skin sites are frequent. Corticotropinomas or somatotropinomas are part of the hereditary syndrome-related pituitary adenomas (representing 5% of all). Primary pigmented nodular adrenocortical disease involves bilateral cortical hyperplasia causing Cushing syndrome (CS) at an earlier age than non-CNC cases; osteoporotic fractures seem more prevalent compare to CS of other etiologies. Typically benign, a few cases of adrenocortical carcinoma have been identified. A total of 5% of familial non-medullary thyroid cancer is syndromic, also including CNC. CNC-related thyroid frame includes: hyperthyroidism, follicular hyperplasia/adenomas, follicular carcinoma (usually aggressive, bilateral or multifocal). Large cell calcifying Sertoli cell tumors of the testes have malignant behavior in adults; in children these may induce precocious puberty. Two particular mammary tumors are found: myxoid fibroadenomas and breast myxomatosis. Cutaneous/subcutaneous lesions, pigmented or not, or any focal swelling of non-identified cause needs careful examination, since dermatological elements are among the earliest and most discernable by which to detect lesions in CNC, a systemic condition with multi-level endocrine involvement. PMID:34630667 | PMC:PMC8461626 | DOI:10.3892/etm.2021.10748 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Prediction of bleeding events using the VTE-BLEED risk score in patients with venous thromboembolism receiving anticoagulant therapy (Review)

xlomafota13 shared this article with you from Inoreader Prediction of bleeding events using the VTE-BLEED risk score in patients with venous thromboembolism receiving anticoagulant therapy (Review) Via Experimental and therapeutic medicine Exp Ther Med. 2021 Nov;22(5):1344. doi: 10.3892/etm.2021.10779. Epub 2021 Sep 22. ABSTRACT Venous thromboembolism (VTE) is a major healthcare problem due to its high incidence, significant mortality rate from pulmonary embolism, high recurrence rate and morbidity from long-term complications. After a first episode of VTE all patients must receive anticoagulant treatment for 3 months. Further anticoagulation is recommended in patients without transient risk factors for VTE or patients with active cancer, if they are not at a high risk for bleeding. The VTE-BLEED risk score was created with the purpose of enabling a better stratification of the bleeding risk during stable anticoagulation after a first VTE. Currently, it is the most validated risk score in VTE settings (selected and non-selected cohorts). It has a good prediction power for major bleeding events in patients receiving any of the currently available classes of oral anticoagu lants, and it can identify patients at risk of intracranial and fatal bleeding events. The aim of our review was to highlight the strengths of the VTE-BLEED risk score, to acknowledge its weak points and to properly position its use in current medical practice. PMID:34630698 | PMC:PMC8495538 | DOI:10.3892/etm.2021.10779 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Gas6/Axl signaling pathway promotes proliferation, migration and invasion and inhibits apoptosis in A549 cells

xlomafota13 shared this article with you from Inoreader Gas6/Axl signaling pathway promotes proliferation, migration and invasion and inhibits apoptosis in A549 cells Via Experimental and therapeutic medicine Exp Ther Med. 2021 Nov;22(5):1321. doi: 10.3892/etm.2021.10756. Epub 2021 Sep 20. ABSTRACT Several studies have demonstrated that growth arrest-specific protein 6 (Gas6) and Axl are highly expressed in various tumor tissues, such as renal cell and esophageal carcinoma. However, the effect of the Gas6/Axl signaling pathway on lung adenocarcinoma is still unclear. The aim of the present study was to investigate the effect of the Gas6/Axl signaling pathway on lung adenocarcinoma cells and its mechanism of action, which may provide a novel target for the clinical treatment of lung adenocarcinoma. Human lung adenocarcinoma tissues were used to examine the activation of the Gas6/Axl signaling pathway. In addition, the human lung adenocarcinoma cell line A549 was employed to study the effects of the Gas6/Axl signaling pathway on the proliferation, migration, invasion and apoptosis of lung adenocarcinoma cells. Recombinant human Gas6 protein a nd inhibitor TP-0903 were used to activate and inhibit the Gas6/Axl signaling pathway, respectively. The results revealed that Gas6 and Axl expression level was increased in human lung adenocarcinoma tissues compared with adjacent healthy tissues. After inhibition of the Gas6/Axl signaling pathway with TP-0903, p21, p53, caspase 3, caspase 8 and caspase 9 exhibited higher expression level in A549 cells. The opposite effect was observed when the Gas6/Axl signaling pathway was activated. In addition, the migratory and invasive ability of A549 cells was determined via wound-healing and Transwell invasion assays. The results indicated that the migratory and invasive ability of A549 cells was significantly increased when the Gas6/Axl signaling pathway was activated and inhibition of Gas6/Axl signaling pathway caused the opposite results. Activity of Gas6/Axl signaling pathway was shown to be positively associated with cell proliferation by Cell Counting Kit 8 and clone formation assays. In conclusion, the Gas6/Axl signaling pathway was revealed to promote the proliferation, migration and invasion and inhibit the apoptosis of lung adenocarcinoma cells, which serve important roles in the progression of lung adenocarcinoma. PMID:34630675 | PMC:PMC8495543 | DOI:10.3892/etm.2021.10756 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Pheochromocytoma as a rare hypertensive complication rarely associated with pregnancy: Diagnostic difficulties (Review)

xlomafota13 shared this article with you from Inoreader Pheochromocytoma as a rare hypertensive complication rarely associated with pregnancy: Diagnostic difficulties (Review) Via Experimental and therapeutic medicine Exp Ther Med. 2021 Nov;22(5):1345. doi: 10.3892/etm.2021.10780. Epub 2021 Sep 22. ABSTRACT This review provides a brief clinically relevant review of pheochromocytoma in pregnancy, to raise awareness among doctors in obstetrics and the aim is to serve as the first point of reference when confronted by their presence. Pheochromocytomas are neuroendocrine, catecholamine-secreting tumours. Despite having the highest incidence rate among other hormone-secreting adrenal tumours, they remain rare especially when associated with pregnancy. The non-specific presentation of pheochromocytomas, the difficulties in their diagnosis during pregnancy as well as the high maternal and fetal mortality rates associated with them, present a challenge. Clinical suspicion and meticulous patient history-taking remain the primary lines of defense, while biochemical proof of catecholamine excess (or their metabolites) and imaging-based localisation of the tumo ur are required for diagnosis. Antenatal diagnosis and complete localisation of the tumour increase the likelihood of successful outcomes for both mother and newborn. Magnetic resonance imaging (MRI) remains the method of choice during pregnancy without excluding the use of ultrasound. Treatment goals should include the avoidance of hypertensive crises while maintaining adequate uteroplacental circulation. The target blood pressure is not strictly defined but is in line with the general guideline addressing chronic hypertension during pregnancy. Antihypertensive medications remain the cornerstone in managing pheochromocytoma. As a first-line, the α-adrenergic, nonselective antagonist phenoxybenzamine is the most frequently used agent, while α1-selective adrenergic antagonists with or without the addition of β- or β1-blockers are also prescribed in certain cases, rendering calcium channel blockers as 'second-choice'. Blood-pressure control of the mother and the well-being of the fetus are determining factors in deciding the time of delivery, which is preferably conducted by Caesarean section. Excision of the tumour(s) remains the final treatment goal. Lifelong biochemical testing is required with or without medical treatment, to address mineralocorticoid or glucocorticoid deficits. Despite ever-improving positive outcome rates, pheochromocytoma associated with pregnancy remains a pathology with high mortality and morbidity rates. PMID:34630699 | PMC: PMC8495583 | DOI:10.3892/etm.2021.10780 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

A systematic review of euthyroid Graves' disease (Review)

xlomafota13 shared this article with you from Inoreader A systematic review of euthyroid Graves' disease (Review) Via Experimental and therapeutic medicine Exp Ther Med. 2021 Nov;22(5):1346. doi: 10.3892/etm.2021.10781. Epub 2021 Sep 22. ABSTRACT Euthyroid Graves' Disease (EGD) is a challenging pathology, due to its atypical clinical manifestations and the absence of abnormal thyroid function. Typically, thyroid ophthalmopathy is associated with elevated thyroid hormone levels and with the presence of thyrotropin receptor antibodies (TRAb) but a low percentage of patients remain euthyroid without developing hyperthyroidism during long-term follow-up periods. Although it is considered a different pathology, it shares a lot of similarities with Graves' disease, rendering the diagnosis more difficult. It is also important to note that ophthalmopathy may be the first clinical manifestation of Graves' disease and that thyroid function examinations do not present abnormalities over a long period. Treatment choices for euthyroid disease do not differ from those described in Graves' ophthalmopath y. However, it is considered that since euthyroid patients develop milder ophthalmic symptoms and their clinical activity score is lower, they tend to have better responses to treatment. Moreover, atypical sight-threatening cases such as exposure keratopathy and dysthyroid optic neuropathy with variable responses to therapy also exist. Disease management consists of a favorable collaboration between ophthalmologists and endocrinologists because patients with EGD can develop thyroid abnormalities over time. In conclusion, the diagnosis of EGD is difficult, clinical manifestations and evolution are variables depending on several factors, including the heterogeneity of TRAb. This review aimed to identify the characteristics of this disease by reviewing the clinical studies and case reports published in previous years. PMID:34630700 | PMC:PMC8495540 | DOI:10.3892/etm.2021.10781 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Effects of isoflavone derivatives on the production of inflammatory cytokines by synovial cells

xlomafota13 shared this article with you from Inoreader Effects of isoflavone derivatives on the production of inflammatory cytokines by synovial cells Via Experimental and therapeutic medicine Exp Ther Med. 2021 Nov;22(5):1300. doi: 10.3892/etm.2021.10735. Epub 2021 Sep 16. ABSTRACT The present study investigated the effects of isoflavone derivatives (daidzein, genistein and glycitein) on the production of inflammatory cytokines (IL-6 and IL-8) by IL-1β-stimulated synovial cells. Synovial MH7A cells were stimulated with IL-1β in the absence or presence of isoflavone derivatives, and IL-6 and IL-8 production was measured by ELISA. The results of the present study indicated that daidzein significantly inhibited the production of IL-6, but not IL-8. Conversely, neither genistein nor glycitein exerted any inhibitory effects on the production of IL-6 or IL-8 by IL-1β-stimulated synovial cells. To elucidate the molecular mechanisms underlying the daidzein-mediated inhibition of IL-6 production, the present study examined the effects of daidzein on the phosphorylation (activation) of NF-κB p65, ERK1/2 and p38 MAPK. Daidzein sig nificantly inhibited the phosphorylation of NF-κB p65 and ERK1/2, but not p38 MAPK in IL-1β-stimulated MH7A cells. The present study revealed that among the isoflavone derivatives examined (daidzein, genistein and glycitein), daidzein inhibited the production of IL-6, but not IL-8, by IL-1β-stimulated synovial MH7A cells via the suppression of NF-κB p65 and ERK1/2 activation. Collectively, these results suggested that daidzein may have potential as a therapeutic agent for the treatment of arthritic disorders through its anti-inflammatory effects via the inhibition of IL-6 production. PMID:34630655 | PMC:PMC8461622 | DOI:10.3892/etm.2021.10735 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.