Αρχειοθήκη ιστολογίου

Τρίτη 22 Ιουνίου 2021

Changes in bone density, intraosseous pressure of distal femoral articular cartilage and subchondral bone after proximal femoral medullary cavity cement filling in rabbits

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Exp Ther Med. 2021 Aug;22(2):839. doi: 10.3892/etm.2021.10271. Epub 2021 Jun 6.

ABSTRACT

Bone cement is widely used, particularly in hip replacements, but the potential clinical complications of its use have been largely unrecognized. The purpose of the present study was to investigate the effects of bone cement in the proximal femoral medullary cavity (PFMC) on bone mineral density (BMD), intraosseous pressure (IOP), articular cartilage and subchondral bone in the distal femurs of rabbits. A total of 32 New Zealand white rabbits were randomly numbered and the left hind limb of the odd-numbered rabbits and the right hind limb of the even numbered rabbits were selected as the experimental side. For each rabbit, the non-experimental hind limb was labeled as the control side by the principal investigator. An intramedullary injection of polymethyl methacrylate was made into the experimental hindlimb of each rabbit and the PFMC filled with bone cement. BMD and IOP of the distal femur of the bilateral hindlimb were measured at 4 and 16 weeks after surgery, and histological and ultra-fine structural features were examined by light and transmission electron microscopy, respectively. At week 4 after the operation, IOP in the experimental limb was significantly higher and BMD lower compared with the control limb. At the 16th week after operation, the IOP in the experimental limb was lower than at the 4th week after operation, but still higher compared with controls, and the BMD was significantly higher than the controls. In the controls, IOP and BMD was not significantly different between the 4th and 16th week after operation. Compared with controls, the cartilage in the experimental group was thinner, the chondrocytes partially necrotic and the trabecular structure of the subchondral bone broken. Analysis of ultra-fine structural features in the experimental group showed chondrocytes with necrotic cytoplasm and pyknotic n uclei relative to controls. The results indicated that blockage of the PFMC with bone cement resulted in an increase in the IOP in the distal femur, a change in BMD and damage to the subchondral bone and articular cartilage.

PMID:34149885 | PMC:PMC8210259 | DOI:10.3892/etm.2021.10271

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Discovery of hydroxytyrosol as thioredoxin reductase 1 inhibitor to induce apoptosis and G1/S cell cycle arrest in human colorectal cancer cells via ROS generation

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Exp Ther Med. 2021 Aug;22(2):829. doi: 10.3892/etm.2021.10261. Epub 2021 Jun 3.

ABSTRACT

Colorectal cancer (CRC) is one of the most common cancer types and a leading cause of cancer-associated mortality in China. Increased thioredoxin reductase 1 (TrxR1) levels have been previously identified as possible target for CRC. The present study revealed that the natural product hydroxytyrosol (HT), which exhibits a polyphenol scaffold, is a potent inhibitor of TrxR1. Inhibition of TrxR1 was indicated to result in accumulation of reactive oxygen species, inhibit proliferation and induce apoptosis and G1/S cell cycle arrest of CRC cells. Using a C-terminal mutant TrxR1 enzyme activity assay, TrxR1 RNA interference assay and HT binding model assay, the present study demonstrated the core character of the selenocysteine residue in the interaction between HT and TrxR1. HT can serve as polyphenol scaffold to develop novel TrxR1 inhibitor s for CRC treatment in the future.

PMID:34149875 | PMC:PMC8200807 | DOI:10.3892/etm.2021.10261

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Pharmacological activities of ginsenoside Rg5 (Review)

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Exp Ther Med. 2021 Aug;22(2):840. doi: 10.3892/etm.2021.10272. Epub 2021 Jun 6.

ABSTRACT

Ginseng, a perennial plant belonging to genus Panax, has been widely used in traditional herbal medicine in East Asia and North America. Ginsenosides are the most important pharmacological component of ginseng. Variabilities in attached positions, inner and outer residues and types of sugar moieties may be associated with the specific pharmacological activities of each ginsenoside. Ginsenoside Rg5 (Rg5) is a minor ginsenoside synthesized during ginseng steaming treatment that exhibits superior pharmaceutical activity compared with major ginsenosides. With high safety and various biological functions, Rg5 may act as a potential therapeutic candidate for diverse diseases. To date, there have been no systematic studies on the activity of Rg5. Therefore, in this review, all available literature was reviewed and discussed to facilitate further re search on Rg5.

PMID:34149886 | PMC:PMC8210315 | DOI:10.3892/etm.2021.10272

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Inhibition of miR-200b-3p alleviates lipid accumulation and promotes cholesterol efflux by targeting ABCA1 in macrophage-derived foam cells

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Exp Ther Med. 2021 Aug;22(2):831. doi: 10.3892/etm.2021.10263. Epub 2021 Jun 3.

ABSTRACT

Atherosclerosis (As) is a chronic cardiovascular disease characterized by abnormal of lipid accumulation and cholesterol efflux. The present study aimed to investigate whether the micro-RNA (miR)-200b-3p could exacerbate As by promoting lipid accumulation and inhibiting cholesterol efflux via ATP-binding cassette transporter A1 (ABCA1) in macrophage-derived foam cells. Blood samples from 30 patients with As and 30 healthy people were collected at Quanzhou First Hospital. RAW264.7 cells were used to establish foam cells using oxidized low-density lipoprotein. The expression of miR-200b-3p and ABCA1 was evaluated by reverse transcription quantitative PCR and western blotting. Lipid accumulation was analyzed by Oil Red O staining and cholesterol content was assessed by ELISA. A targeting relationship between miR-200b-3p and ABCA1 was demonstrated by l uciferase reporter assays. Compared with healthy volunteers and RAW264.7 cells, the expression level of miR-200b-3p was significantly increased whereas the expression level of ABCA1 was significantly decreased in patients with As and foam cells. Furthermore, miR-200b-3p expression was negatively correlated with ABCA1 expression in the blood of the patients with As. Lipid content was significantly decreased and cholesterol efflux was significantly increased in foam cells transfected with the miR-200b-3p inhibitor compared with inhibitor control cells. In addition, ABCA1 was shown to be targeted by miR-200b-3p. Furthermore, the lipid content in foam cells transfected with the miR-200b-3p inhibitor and small interfering-ABCA1 was significantly increased, while the cholesterol efflux was significantly decreased compared with foam cells transfected with the miR-200b-3p inhibitor. In conclusion, the findings from the present study indicated that inhibition of miR-200b-3p may alleviate lip id accumulation and promote cholesterol efflux by targeting ABCA1 in macrophage-derived foam cells.

PMID:34149877 | PMC:PMC8200800 | DOI:10.3892/etm.2021.10263

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Pharmacological inhibition of EZH2 by GSK126 decreases atherosclerosis by modulating foam cell formation and monocyte adhesion in apolipoprotein E-deficient mice

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Exp Ther Med. 2021 Aug;22(2):841. doi: 10.3892/etm.2021.10273. Epub 2021 Jun 6.

ABSTRACT

Histone modifications play an important role in the occurrence and development of atherosclerosis in human and atherosclerosis-prone mice. Histone methylation in macrophages, monocytes and endothelial cells markedly influence the progression of atherosclerosis. However, it remains unclear whether treatment with a histone methyltransferase enhancer of zeste homolog 2 (EZH2) inhibitor may suppress atherosclerosis. The present study aimed to determine the effects of the EZH2 inhibitor, GSK126, on the suppression and regression of atherosclerosis in apolipoprotein E-deficient mouse models. In vitro, it was found that pharmacological inhibition of EZH2 by GSK126 markedly reduced lipid transportation and monocyte adhesion during atherogenesis, predominantly through increasing the expression levels of ATP-binding cassette transporter A1 and suppres sing vascular cell adhesion molecule 1 in human THP-1 cells. In vivo, it was found that atherosclerotic plaques in GSK126-treated mice were significantly decreased when comparing with the vehicle-treated animals. These results indicated that the GSK126 has the ability to attenuate the progression of atherosclerosis by reducing macrophage foam cell formation and monocyte adhesion in cell and mouse models. In conclusion, the present study provided new insights into the molecular mechanism behind the action of GSK126 and suggested its therapeutic potential for the treatment of atherosclerosis.

PMID:34149887 | PMC:PMC8210282 | DOI:10.3892/etm.2021.10273

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Protective role and molecular mechanism of action of Nesfatin-1 against high glucose-induced inflammation, oxidative stress and apoptosis in retinal epithelial cells

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Exp Ther Med. 2021 Aug;22(2):833. doi: 10.3892/etm.2021.10265. Epub 2021 Jun 3.

ABSTRACT

Diabetic retinopathy (DR) is a major complication of diabetes mellitus that may cause severe visual impairment. It has been reported that the levels of nesfatin-1 in the serum and vitreous humor were negatively correlated with DR; however, its role in DR has not been fully elucidated. Therefore, the present study was performed to investigate the effect of nesfatin-1 on high glucose-treated human retinal epithelial cells (ARPE-19) and explore the underlying mechanism. The effects of nesfatin-1 on cell viability, inflammation, oxidative stress and apoptosis were examined under high glucose conditions. The Cell Counting Kit-8 assay was used to determine cell viability. The levels of inflammatory cytokines were evaluated using ELISA kits. The reactive oxygen species and malondialdehyde content was estimated using commercial assay kits. Flow cytometry w as performed to detect apoptotic cells and western blot analysis was employed to evaluate the expression of apoptosis-associated proteins. Moreover, the levels of NF-κB, NACHT, LRR and PYD domains-containing protein 3 (NLRP3) and high-mobility group protein B1 (HMGB1) were determined via western blot analysis. The results revealed that nesfatin-1 enhanced cell viability and suppressed inflammation, oxidative stress and apoptosis in the presence of high glucose concentration. Moreover, the activation of the NF-κB/NLRP3 inflammasome signaling and the expression of HMGB1 were inhibited by nesfatin-1. Furthermore, HMGB1 overexpression partially abrogated the inactivation of the NF-κB/NLRP3 inflammasome pathway caused by nesfatin-1. Taken together, these findings demonstrated that nesfatin-1 inhibited the activation of the NF-κB/NLRP3 inflammasome signaling via modulating HMGB1 and exerted a protective effect on ARPE-19 cells against high glucose-induced inflammation, oxidative stres s and apoptosis.

PMID:34149879 | PMC:PMC8200809 | DOI:10.3892/etm.2021.10265

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Inhibitory effects of quercetin and its major metabolite quercetin-3-O-β-D-glucoside on human UDP-glucuronosyltransferase 1A isoforms by liquid chromatography-tandem mass spectrometry

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Exp Ther Med. 2021 Aug;22(2):842. doi: 10.3892/etm.2021.10274. Epub 2021 Jun 6.

ABSTRACT

Quercetin is a flavonoid that is widely present in plant-derived food. Quercetin-3-O-β-D-glucoside (Q3GA) is a predominant metabolite of quercetin in animal and human plasma. The inhibitory effects of the UDP-glucuronosyl transferases (UGTs) caused by herbal components may be a key factor for the clinical assessment of herb-drug interactions (HDIs). The present study aimed to investigate the inhibitory profile of quercetin and Q3GA on recombinant UGT1A isoforms in vitro. The metabolism of the nonspecific substrate 4-methylumbelliferone (4-MU) by the UGT1A isoforms was assessed by liquid chromatography-tandem mass spectrometry. Preliminary screening experiments indicated that quercetin exhibited stronger inhibitory effects on UGT1A1, UGT1A3, UGT1A6 and UGT1A9 enzymes than Q3GA. Kinetic experiments were performed to characterize the type of i nhibition caused by quercetin and Q3GA towards these UGT isoforms. Quercetin exerted non-competitive inhibition on UGT1A1 and UGT1A6, with half maximal inhibitory concentration (IC50) values of 7.47 and 7.07 µM and inhibition kinetic parameter (Ki) values of 2.18 and 28.87 µM, respectively. Quercetin also exhibited competitive inhibition on UGT1A3 and UGT1A9, with IC50 values of 10.58 and 2.81 µM and Ki values of 1.60 and 0.51 µM, respectively. However, Q3GA displayed weak inhibition on UGT1A1, UGT1A3 and UGT1A6 enzymes with IC50 values of 45.21, 106.5 and 51.37 µM, respectively. In the present study, quercetin was a moderate inhibitor of UGT1A1 and UGT1A3, a weak inhibitor of UGT1A6, and a strong inhibitor on UGT1A9. The results of the present study suggested potential HDIs that may occur following quercetin co-administration with drugs that are mainly metabolized by UGT1A1, UGT1A3 and UGT1A9 enzymes.

PMID:34149888 | PMC:PMC8210293 | DOI:10.3892/etm.2021.10274

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lncRNA ZFAS1 promotes the ox-LDL induced proliferation, invasion and migration of vascular smooth muscle cells

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Exp Ther Med. 2021 Aug;22(2):835. doi: 10.3892/etm.2021.10267. Epub 2021 Jun 4.

ABSTRACT

Atherosclerosis is a chronic progressive inflammatory vascular disease. The dysfunction of vascular smooth muscle cells (VSMCs) induced by oxidized low-density lipoprotein (ox-LDL) contributes to the formation of atherosclerotic lesions. Additionally, upregulation of the long non-coding RNA zinc finger antisense 1 (ZFAS1) was observed in the plaques of patients with atherosclerosis. The aim of the present study was to explore the functional role of ZFAS1 in atherosclerosis progression. Reverse transcription-quantitative PCR was performed to analyze ZFAS1 mRNA expression, and western blotting was performed to determine the protein expression levels of Ki67, proliferating cell nuclear antigen (PCNA), matrix metallopeptidase (MMP)2 and MMP9. The Cell Counting Kit-8 assay was used to test cell viability. Finally, wound healing and Transwell chamber ass ays were performed to evaluate cell migration and invasion, respectively. The current findings demonstrated that ZFAS1 expression was upregulated by ox-LDL stimulation in VSMCs. Moreover, ZFAS1 overexpression promoted the ox-LDL-induced proliferation, migration and invasion of VSMCs, and upregulated the expression levels of proteins associated with cellular proliferation (Ki67 and PCNA), migration and invasion (MMP2 and 9). By contrast, ZFAS1-knockdown inhibited the proliferation, migration and invasion of VSMCs, and suppressed cell proliferation-, migration- and invasion-associated protein expression. In conclusion, ZFAS1 promoted the ox-LDL-induced proliferation, invasion and migration of VSMCs. Thus, ZFAS1 may represent a novel biomarker for dysfunction of VSMCs in the pathological condition of atherosclerosis.

PMID:34149881 | PMC:PMC8200810 | DOI:10.3892/etm.2021.10267

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Δευτέρα 21 Ιουνίου 2021

Acute inferior myocardial infarction in a young man with testicular seminoma: A case report

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World J Clin Cases. 2021 Jun 6;9(16):4040-4045. doi: 10.12998/wjcc.v9.i16.4040.

ABSTRACT

BACKGROUND: Atherosclerosis represents the main cause of myocardial infarction (MI); other causes such as coronary embolism, vasospasm, coronary-dissection or drug use are much rarely encountered, but should be considered in less common clinical scenarios. In young individuals without cardiovascular risk factors, the identification of the cause of MI can sometimes be found in the medical history and previous treatments undertaken.

CASE SUMMARY: We present the case of a 34-year-old man presenting acute inferior ST-elevation MI without classic cardiac risk factors. Seven years ago, he suffered from orchidopexy for bilateral cryptorchidism, and was recently diagnosed with right testicular seminoma for which he had to undergo surgical resection and chemotherapy with bleomycin, etoposide and cisplatin. Shortly after the first chemotherapy treatmen t, namely on day five, he suffered an acute MI. Angiography revealed a mild stenotic lesion at the level of the right coronary artery with suprajacent thrombus and vasospasm, with no other significant lesions on the other coronary arteries. A conservative treatment was decided upon by the cardiac team, including dual antiplatelets therapy and anticoagulants with good further evolution. The patient continued the chemotherapy treatment according to the initial plan without other cardiovascular events.

CONCLUSION: In young individuals with no cardiovascular risk factors undergoing aggressive chemotherapy, an acute MI can be caused by vascular toxicity of several anti-cancer drugs.

PMID:34141764 | PMC:PMC8180225 | DOI:10.12998/wjcc.v9.i16.4040

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Dynamic magnetic resonance imaging features of cavernous hemangioma in the manubrium: A case report

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World J Clin Cases. 2021 Jun 16;9(17):4262-4267. doi: 10.12998/wjcc.v9.i17.4262.

ABSTRACT

BACKGROUND: Osseous hemangiomas, especially those located in the manubrium, are rare benign tumors. In a review of the literature, only three case reports of sternal hemangioma were found. A precise diagnosis is difficult because of their nonspecific findings on computed tomography (CT)/magnetic resonance imaging (MRI).

CASE SUMMARY: An 88-year-old woman was suffering from a progressively enlarging mass in the manubrium. Chest CT images showed an osteolytic and expansile lesion with cortical destruction. Vascular malformation was suspected after CT-guided biopsy. On the dynamic MRI scans, the mass showed a bright signal on the T2-weighted image, peripheral nodular enhancement on the early-phase images and progressive centripetal fill-in on the delayed-phase images. Cavernous hemangioma was suspected preoperatively based on the MRI features a nd finally confirmed by histopathologic analysis.

CONCLUSION: This uncommon case demonstrates the possible characteristic features of manubrium cavernous hemangioma on dynamic MRI scans; knowledge about these features may prevent patients from developing catastrophic complications, such as rupture or internal hemorrhage, caused by biopsy or surgery.

PMID:34141789 | PMC:PMC8173419 | DOI:10.12998/wjcc.v9.i17.4262

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Parotid mammary analogue secretory carcinoma: A case report and review of literature

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World J Clin Cases. 2021 Jun 6;9(16):4052-4062. doi: 10.12998/wjcc.v9.i16.4052.

ABSTRACT

BACKGROUND: Mammary analogue secretory carcinoma (MASC) is a rare low-grade malignant salivary gland tumor. The morphological and immunohistochemical features of MASC closely resemble those of breast secretory carcinoma. The key characteristics of the lesion are a lack of pain and slow growth. There is no obvious specificity in the clinical manifestations and imaging features. The diagnosis of the disease mainly depends on the detection of the MASC-specific ETV6-NTRK3 fusion gene.

CASE SUMMARY: This report describes a rare case of a 32-year-old male patient who presented with a gradually growing lesion that was initially diagnosed as breast-like secretory carcinoma of the right parotid gland. Imaging and histological investigations were used to overcome the diagnostic difficulties. The lesion was managed with right parotidectomy, facia l nerve preservation, biological patch implantation to restore the resulting defect, and postoperative radiotherapy. On postoperative follow-up, the patient reported a mild facial deformity with no complications, signs of facial paralysis, or Frey's syndrome.

CONCLUSION: The imaging and histological diagnostic challenges for MASC are discussed.

PMID:34141766 | PMC:PMC8180236 | DOI:10.12998/wjcc.v9.i16.4052

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