Wednesday, March 23, 2022

MicroRNA-302 inhibits cell migration and invasion in cervical cancer by targeting DCUN1D1

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Exp Ther Med. 2022 Apr;23(4):298. doi: 10.3892/etm.2022.11227. Epub 2022 Feb 21.

ABSTRACT

[This retracts the article DOI: 10.3892/etm.2018.6223.].

PMID:35317449 | PMC:PMC8908467 | DOI:10.3892/etm.2022.11227

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miR-150-5p inhibits osteogenic differentiation of fibroblasts in ankylosing spondylitis by targeting VDR

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Exp Ther Med. 2022 Apr;23(4):283. doi: 10.3892/etm.2022.11213. Epub 2022 Feb 15.

ABSTRACT

Dysregulated microRNAs (miRNAs or miRs) serve potential roles in inflammatory systemic disease, including ankylosing spondylitis (AS). The aim of the present study was to investigate the potential function of miR-150-5p in osteogenic differentiation of AS fibroblasts and its underlying mechanism. The expression of miR-150-5p and vitamin D receptor (VDR) in AS joint capsules and fibroblasts was detected by reverse transcription-quantitative (RT-q)PCR and western blotting. Following overexpression of miR-150-5p, the alteration in osteogenic gene expression was detected by RT-qPCR, western blotting and alkaline phosphatase activity assay, as well as alizarin red staining. The association between miR-150-5p and VDR was confirmed by luciferase assay and rescue experiments were performed. Patients with AS exhibited decreased expression of miR-150-5p in joint capsules. Treatment with bone morphogenic protein 2 (BMP-2) and transforming growth factor-β1 (TGF-β1) led to downregulation of miR-150-5p in AS fibroblasts. Enforced expression of miR-150-5p attenuated osteogenic differentiation of AS fibroblasts. These results demonstrated that miR-150-5p inhibited osteogenic differentiation of AS fibroblasts by targeting VDR. miR-150-5p overexpression decreased osteogenic transformation of fibroblasts by decreasing VDR expression in AS.

PMID:35317439 | PMC:PMC8908459 | DOI:10.3892/etm.2022.11213

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Micropulse vs. continuous wave transscleral cyclophotocoagulation in neovascular glaucoma

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Exp Ther Med. 2022 Apr;23(4):278. doi: 10.3892/etm.2022.11207. Epub 2022 Feb 11.

ABSTRACT

Neovascular glaucoma (NVG) is a refractory form of glaucoma, associated with important morbidity, for which no consensus exists regarding the optimal choice of therapy. The primary aim of our study was to compare the performances of micropulse transscleral cyclophotocoagulation (MP-TSCPC) and continuous wave transscleral cyclophotocoagulation (CW-TSCPC) in the treatment of neovascular glaucoma (NVG). A total of 24 eyes for MP-TSCPC and 22 eyes for CW-TSCPC, all with NVG were included. The procedures were performed using either the Iridex Cyclo G6 (IRIDEX Laser System), the MP3, or the G-Probe devices. Intraocular pressure (IOP), visual acuity (VA), the mean number of antiglaucoma medications, and postoperative complications were monitored. The minimum follow-up was 12 months. The success rate at 12 months was 54.5% in the CW-TSCPC group and 33.3% in the MP-TSCPC group. The mean IOP at baseline was 35.82 mm Hg for CW-TSCPC and 34.71 mm Hg for MP-TSCPC. The change from baseline in IOP at 12 months was 11.95 mm Hg in the CW-TSCPC group and -8.04 mm Hg in the MP-TSCPC group. There was a significant difference in the occurrence of serious complications (worsening of VA, hypotony, and phthisis bulbi) between the two methods, with CW-TSCPC associated with more important adverse effects (P=0.045). There was a decrease in the number of topical antiglaucoma medications in both groups: in the MP-TSCPC group from a mean number of 2.6 at baseline, to 1.7 at 3 months, followed by a slight increase to 2.1 at 12 months and in the CW-TSCPC group from 2.8 at baseline, to 1.4 at 3 months and 1.9 at 12 months. Our study concluded that both MP-TSCPC and CW-TSCPC could manage NVG, but, while CW-TSCPC revealed higher IOP control in the long term (which did not reach statistical significance), it also had a significantly lower safety profile.

PMID:35317447 | PMC:PMC8908348 | DOI:10.3892/etm.2022.11207

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Circular RNA hsa_circ_0011946 promotes the malignant process of salivary adenoid cystic carcinoma by downregulating miR-1205 expression

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Exp Ther Med. 2022 Apr;23(4):295. doi: 10.3892/etm.2022.11224. Epub 2022 Feb 18.

ABSTRACT

Circular RNA (circRNA/circ) hsa_circ_0011946 has been reported to serve an important role in a number of cancer types; however, to the best of our knowledge, its role in salivary adenoid cystic carcinoma (SACC) has not been reported. In the present study, the primary focus was the effects of hsa_circ_0011946 on the invasion, migration and epithelial-mesenchymal transformation (EMT) of SACC cells, and the specific mechanisms involved. The expression levels of hsa_circ_0011946 and microRNA (miR)-1205 in cancer tissues and paracancerous tissues of patients with SACC were analyzed using reverse transcription-quantitative (RT-q)PCR. The cell proliferation rate was determined using a Cell Counting Kit-8 assay. Wound healing assays were performed to analyze the cell migratory ability, while a transwell assay was used to measure the cell invasion ability. Western blotting was used to analyze the expression levels of EMT-related proteins. Cell transfection was used to knockdown hsa_circ_0011946 and knockdown or overexpress miR-1205. Subcellular localization assays for hsa_circ_0011946 were performed using RT-qPCR. A dual-luciferase reporter gene assay was used to verify the binding between hsa_circ_0011946 and miR-1205. The results of the present study revealed that the expression levels of hsa_circ_0011946 were significantly upregulated in cancer tissues from patients with SACC. The knockdown of hsa_circ_0011946 expression inhibited the proliferation, invasion and migration of SACC cells, thereby inhibiting the EMT process, which was achieved by downregulating miR-1205 expression. In conclusion, circRNA hsa_circ_0011946 was discovered to promote the malignant process of SACC by downregulating miR-1205 expression.

PMID:35317442 | PMC:PMC8908474 | DOI:10.3892/etm.2022.11224

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Anagliptin promotes apoptosis in mouse colon carcinoma cells via MCT-4/lactate-mediated intracellular acidosis

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Exp Ther Med. 2022 Apr;23(4):282. doi: 10.3892/etm.2022.11211. Epub 2022 Feb 15.

ABSTRACT

Cancer cells frequently exhibit an acidic extracellular microenvironment, where inversion of the transmembrane pH gradient is associated with tumor proliferation and metastasis. To elucidate a new therapeutic target against cancer, the current study aimed to determine the mechanism by which the dipeptidyl peptidase-4 inhibitor anagliptin regulates the cellular pH gradient and concomitant extracellular acidosis during cancer progression. A total of 5x105 CT-26 cells (resuspended in phosphate buffer saline) were injected subcutaneously in the right flank of male BALB/c mice (weighing 25-28 g). The tumor samples were harvested, and lactate was detected using a lactate assay kit. Immunohistochemistry was used to detect the Ki67 and PCNA. MTT assay and flow cytometric were used to detect cell viability. Intracellular pH was detected by fluor escence pH indicator. The results revealed that anagliptin effectively reduced tumor growth, but did not affect the body weight of treated mice. Anagliptin reduced the accumulation of lactate in tumor sample. Treatment with anagliptin stimulated the apoptosis of CT-26 cells. And lactate excretion inhibition is accompanied by an increase in extracellular pH (pHe) after treatment with anagliptin. Furthermore, anagliptin induced intracellular acidification and reversed the low pHe gradient via monocarboxylate transporter-4 (MCT-4)-mediated lactate excretion. Additionally, anagliptin reversed the aberrant transmembrane extracellular/intracellular pH gradient by suppressing MCT-4-mediated lactate excretion, while also reducing mitochondrial membrane potential and inducing apoptosis. These data revealed a novel function of anagliptin in regulating lactate excretion from cancer cells, suggesting that anagliptin may be used as a potential treatment for cancer.

PMID:35317435 | PMC:PMC8908463 | DOI:10.3892/etm.2022.11211

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pH regulates the lumen diameter of tissue-engineered capillaries

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Exp Ther Med. 2022 Apr;23(4):284. doi: 10.3892/etm.2022.11212. Epub 2022 Feb 15.

ABSTRACT

Angiogenesis is vital in tissue engineering and the size of the capillary lumen diameter directly affects vascular function. Therefore, the involvement of the pH in the regulation of the capillary lumen diameter was investigated in the present study. The cytosolic pH of different pH medium groups was measured using flow cytometry. Bromodeoxyuridine staining and wound-healing assays were performed to detect cell proliferation and migration, respectively. The expression of angiogenesis-related genes was detected using reverse transcription-quantitative PCR. In addition, cell tube formation under different pH conditions was assessed using a tube formation assay and a 3D Matrigel® model. The results indicated that a change in the pH value of the culture medium affected the cytosolic pH of the endothelial cells, which then led to a change i n vascular diameter. When the medium's pH ranged from 7.4 to 7.6, the diameter of the lumen formed in the Matrigel was suitable for capillary formation in tissue engineering. The present results revealed an important role for the pH in the process of capillary formation and provided insight for pH regulation during endothelial cell tube formation and angiogenesis in tissue engineering.

PMID:35317437 | PMC:PMC8908470 | DOI:10.3892/etm.2022.11212

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Diabetes mellitus: Plasticizers and nanomaterials acting as endocrine-disrupting chemicals (Review)

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Exp Ther Med. 2022 Apr;23(4):288. doi: 10.3892/etm.2022.11217. Epub 2022 Feb 16.

ABSTRACT

Various plasticizers and nanomaterials have been linked to endocrine disruptors or endocrine-disrupting chemicals (EDCs) which represent a large, heterogeneous, yet incompletely understood group of structures acting on normal and pathological body pathways such as hormonal production, secretion, transport and receptor binding. By contrast, various applications of nanoparticles are currently under investigation since the delivery of useful drugs, particularly insulin in diabetes mellitus, is essential in case of insulin deficiency. The aim of the present review was to introduce and examine different plasticizers and nanomaterials with potential applications for diabetic patients (such as selenium or gold-based nanoparticles that help the oral delivery of insulin) or plasticizers/nanomaterials acting similarly to EDCs in relation to the human and an imal body, particularly glucose metabolism impairment such as diabetes mellitus (DM). Bisphenol A is a chemical used worldwide; however, the effect of exposure varies with regard to the source, environment, time of exposure and the age of the organism. Daily exposure is mostly related to food and drinks stored in polycarbonate plastics. However, exposure may also be through the skin or through the maternal placenta or breast milk which are risk factors for the fetus and for the newborn. It exerts an estrogen-like profile, but it also induces insulin resistance by impairing peripheral insulin receptors or it decreases insulin secretion by acting at the level of insulin-secreting pancreatic β-cells. Phthalates, compounds of flexible plastics, act as EDCs via their human metabolites such as diethyl phthalate and derivative monoethyl phthalate. Their role in inducing gestational DM and weight gain/obesity during pregnancy has been showcased. The vast field of plasticizers and nanomolec ules acting as endocrine disruptors is widely linked to clinical aspects of DM, a serious condition with a major population impact. The importance of understanding and using these agents and applications is reflected in saving numerous human lives.

PMID:35317436 | PMC:PMC8908456 | DOI:10.3892/etm.2022.11217

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Language lateralization and outcome in perinatal stroke patients with different vascular types

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Publication date: May 2022

Source: Brain and Language, Volume 228

Author(s): Nigul Ilves, Mairi Männamaa, Rael Laugesaar, Norman Ilves, Dagmar Loorits, Ulvi Vaher, Pille Kool, Pilvi Ilves

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Neuroradiological Basis of COVID‐19 Olfactory Dysfunction: A Systematic Review and Meta‐Analysis

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Objective

Olfactory dysfunction (OD) is a common presenting symptom of COVID-19 infection. Radiological imaging of the olfactory structures in patients with COVID-19 and OD can potentially shed light on its pathogenesis, and guide clinicians in prognostication and intervention.

Methods

PubMed, Embase, Cochrane, SCOPUS were searched from inception to August 1, 2021. Three reviewers selected observational studies, case series, and case reports reporting radiological changes in the olfactory structures, detected on magnetic resonance imaging, computed tomography, or other imaging modalities, in patients aged ≥18 years with COVID-19 infection and OD, following preferred reporting items for systematic reviews and meta-analyses guidelines and a PROSPERO-registered protocol (CRD42021275211). We described the proportion of radiological outcomes, and used random-effects meta-analyses to pool the prevalence of olfactory cleft opacification, olfactory bulb signal abnormalities, and olfactory mucosa abnormalities in patients with and without COVID-19-associated OD.

Results

We included 7 case–control studies (N = 353), 11 case series (N = 154), and 12 case reports (N = 12). The pooled prevalence of olfactory cleft opacification in patients with COVID-19 infection and OD (63%, 95% CI = 0.38–0.82) was significantly higher than that in controls (4%, 95% CI = 0.01–0.13). Conversely, similar proportions of cases and controls demonstrated olfactory bulb signal abnormalities (88% and 94%) and olfactory mucosa abnormalities (2% and 0%). Descriptive analysis found that 55.6% and 43.5% of patients with COVID-19 infection and OD had morphological abnormalities of the olfactory bulb and olfactory nerve, respectively, while 60.0% had abnormal olfactory bulb volumes.

Conclusion

Our findings implicate a conductive mechanism of OD, localized to the olfactory cleft, in approximately half of the affected COVID-19 patients. Laryngoscope, 2022

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Effectiveness of gabapentin in reducing opioid requirements after radiation in head and neck cancer in a single institution

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Abstract

Background

Gabapentin has been shown to reduce opioid use in head and neck cancer patients. Here, we examine the efficacy of prophylactic gabapentin at reducing opioid use in these patients at our institution.

Methods

A retrospective study of patients receiving radiation was performed, using patients from our previous study as controls. Risk factors for opioid use at 3 and 6 months were determined using univariate and multivariate analyses.

Results

In total, 53/185 patients were treated with gabapentin, 39.6% of which took opioids at 3 months vs. 58.3% in the non-gabapentin cohort (p = 0.021). Gabapentin was independently associated with less opioid use on multivariate analysis at 3 months (OR 0.47, 95% CI 0.24–0.9). Gastrostomy tube dependence and pretreatment opioid use were associated with chronic opioid use despite gabapentin.

Conclusions

Gabapentin is effective at expediting opioid tapering in head and neck cancer patients who are not gastrostomy tube dependent or taking opioids pretreatment.

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Radiologic–pathologic correlation of major versus minor extranodal extension in oral cavity cancer

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Abstract

Background

To evaluate the diagnostic performance of radiologic extranodal extension (rENE) in predicting major (>2 mm) and minor (≤2 mm) pathologic ENE (pENE).

Methods

All oral cavity squamous cell carcinoma patients who underwent neck dissection with pathological nodal disease (pN+) between 2010 and 2015 were reviewed. Preoperative computed tomography and/or magnetic resonance imaging were reviewed by two head and neck neuroradiologists.

Results

Three hundred and thirty-four patients were included. The sensitivity and specificity of rENE were 37% [95% CI 29–44] and 98% [95% CI 96–100], respectively. Sensitivity for pENE improved in the subset of patients with major ENE (48% [95% CI 38–57]). The presence of rENE was associated with inferior 3-year overall survival: 26% [95% CI 17–41] versus 60% [95% CI 54–67].

Conclusions

This large cohort study demonstrates high specificity, but low sensitivity for preoperative imaging in the detection of pENE in OCSCC. Patients with rENE demonstrated poor OS. pENE in the absence of rENE is still an adverse risk factor.

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