Πέμπτη 18 Μαρτίου 2021

Piperine protects against myocardial ischemia/reperfusion injury by activating the PI3K/AKT signaling pathway

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Exp Ther Med. 2021 Apr;21(4):374. doi: 10.3892/etm.2021.9805. Epub 2021 Feb 19.

ABSTRACT

Piperine (PIP) exerts numerous pharmacological effects and its involvement in endoplasmic reticulum (ER) stress (ERS)-led apoptosis has garnered attention. The present study focused on whether PIP played protective effects on hypoxia/reoxygenation (H/R)-induced cardiomyocytes by repressing ERS-led apoptosis. The potential molecular mechanisms in association with the PI3K/AKT signaling pathway were investigated. Primary neonatal rat cardiomyocytes (NRCMs) were isolated and randomized into four groups: Control + vehicle group, control + PIP group, H/R + vehicle group and H/R + PIP group. The H/R injury model was constructed by 4 h of hypoxia induction followed by 6 h of reoxygenation. A total of 10 µM PI3K/AKT inhibitor LY294002 was supplemented to the cells during the experiments. Cell viability and myocardial enzymes were detected to evaluate myoc ardial damage. A flow cytometry assay was performed to assess apoptotic response. Western blot analysis was performed to detect the expression of related proteins including PI3K, AKT, CHOP, GRP78 and cleaved caspase-12. The results showed that H/R markedly promoted myocardial damage as shown by the increased release of lactate dehydrogenase and creatine kinase levels, but a reduction in cell viability. In addition, ERS-induced apoptosis was markedly promoted by H/R in NRCMs, as shown by the increased apoptotic rates and expression of C/EBP-homologous protein, endoplasmic reticulum chaperone BiP and caspase-12. PIP administration reversed cell injury and ERS-induced apoptosis in H/R. Mechanistic studies concluded that the apoptosis-inhibitory contributions and cardio-favorable effects of PIP were caused partly by the activation of the PI3K/AKT signaling pathway, which was verified by LY294002 administration. To conclude, PIP can reduce ERS-induced apoptosis by activating the PI3K/AKT signaling pathway during the process of H/R injury, which could be a potential therapeutic target for the treatment of myocardial ischemia/reperfusion injury.

PMID:33732347 | PMC:PMC7903478 | DOI:10.3892/etm.2021.9805

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Anti-demodectic effects of okra eyelid patch in Demodex blepharitis compared with tea tree oil

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Exp Ther Med. 2021 Apr;21(4):338. doi: 10.3892/etm.2021.9769. Epub 2021 Feb 10.

ABSTRACT

Demodex infection gradually develops to Demodex blepharitis, which is characterized as chronic inflammation of the eyelid and meibomian gland (MG) and ultimately leads to MG dysfunction. In the present prospective study, the anti-demodectic effects of an okra eyelid patch in patients Demodex blepharitis were investigated. A total of 52 patients with Demodex blepharitis with ocular discomfort were recruited. Patients were randomized to receive either an okra eyelid patch treatment (treatment group, n=27) or tea tree oil (TTO) eye care patch treatment (control group, n=25) for three months. The Demodex count, the ocular surface disease index (OSDI) score, MG expressibility (MGE) and meibum quality, Schirmer I test (SIT), tear break-up time (TBUT) and corneal fluorescein staining (CFS) were determined prior to treatm ent and after 1 and 3 months of treatment. Changes in the parameters were compared between the treatment group and control group after 1 and 3 months of treatment. The average survival time in the okra group was 115.25±11.87 min, which was significantly lower compared with the average ST of 378.75±37.94 min in the blank group (P<0.01). After 3 months of okra eyelid patch treatment, the Demodex count was significantly reduced from 10.15±4.53 to 1.30±1.41 (P<0.01) and the OSDI score of the patients was reduced by 16.84±10.17 (P<0.01). There was no significant difference in the Demodex count (P=0.716) and OSDI (P=0.873) between the treatment and control groups. The rate of complete Demodex eradication in the treatment group (11/27, 40.74%) was slightly lower than that in the control group (12/25, 48%), but there was no significant difference between the two groups (χ2=0.277, P=0.598). Regarding the other ocular parameters, no significant d ifference was observed in the TBUT, meibum quality and MGE between the two groups (P<0.05). TTO group has a significantly improvement compared with Okra group in terms of SIT (P=0.035) and CFS (P=0.023). In conclusion, okra eyelid patch treatment is able to significantly eradicate ocular Demodex as well as markedly alleviate ocular symptoms. Due to causing less irritation than TTO, the okra eyelid patch may be more suitable for sensitive patients with Demodex blepharitis, such as the elderly and children. The study was registered as a clinical trial in the Chinese Clinical Trial Registry (ChiCTR) in November 2018 (registration no. ChiCTR-1,800,019,466).

PMID:33732311 | PMC:PMC7903416 | DOI:10.3892/etm.2021.9769

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A clinical study on the factors associated with nasopharyngeal carcinoma among the Chinese population

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Exp Ther Med. 2021 Apr;21(4):375. doi: 10.3892/etm.2021.9806. Epub 2021 Feb 19.

ABSTRACT

Nasopharyngeal carcinoma (NC) arises from the nasopharynx epithelium and the majority of NC cases globally are within China and Southeast Asia. Both short palate lung and nasal epithelium clone 1 (SPLUNC1) and myelodysplasia syndrome 1-ectopic viral integration site 1 (MDS1-EVI1) play an important role in carcinogenesis and have been found to be associated with nasopharyngeal carcinoma. In spite of their role in NC, the association between these genes and their polymorphisms in the development of NC has thus far not been studied. In the present study, the relationship between SPLUNC1 (rs2752903, T>C) and MDS1-EVI1 (rs6774494, G>A) polymorphisms and their role in the development of NC among the Chinese population were investigated. From a Chinese population of 1,059 patients with NC and 891 controls, genotype frequencies and the distribution o f SPLUNC1 and MDS1-EVI1 polymorphisms were analyzed for possible susceptibility to NC. It was observed that those with MDS1-EVI1 CC (OR, 2.76; 95% CI, 1.96-3.81) and MDS1-EVI1 CT (OR, 1.51; 95% CI, 1.22-2.14) polymorphisms had an increased risk of developing NC. Those with SPLUNC1 AA genotypes also observed a higher risk for NC compared with SPLUNC1 GG genotypes (OR, 2.15; 95% CI, 1.62-3.15). When observing the gene-gene interaction between SPLUNC1 and MDS1-EVI1 polymorphisms, it was found that the presence of both SPLUNC1 CC and MDS1-EVI1 AA alleles was associated with a higher risk for NC compared with those who did not carry both alleles (OR, 6.75; 95% CI, 3.41-12.11). The present study suggested that the association between SPLUNC1 (rs2752903, T>C) and MDS1-EVI1 (rs6774494, G>A) polymorphisms may be a potent risk factor in the occurrence of NC.

PMID:33732348 | PMC:PMC7903443 | DOI:10.3892/etm.2021.9806

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Screening and verification of hub genes involved in osteoarthritis using bioinformatics

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Exp Ther Med. 2021 Apr;21(4):330. doi: 10.3892/etm.2021.9761. Epub 2021 Feb 8.

ABSTRACT

Osteoarthritis (OA) is one of the most common causes of disability and its development is associated with numerous factors. A major challenge in the treatment of OA is the lack of early diagnosis. In the present study, a bioinformatics method was employed to filter key genes that may be responsible for the pathogenesis of OA. From the Gene Expression Omnibus database, the datasets GSE55457, GSE12021 and GSE55325 were downloaded, which comprised 59 samples. Of these, 30 samples were from patients diagnosed with osteoarthritis and 29 were normal. Differentially expressed genes (DEGs) were obtained by downloading and analyzing the original data using bioinformatics. The Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathways were analyzed using the Database for Annotation, Visualization and Integrated Discovery online database. Pr otein-protein interaction network analysis was performed using the Search Tool for the Retrieval of Interacting Genes/proteins online database. BSCL2 lipid droplet biogenesis associated, seipin, FOS-like 2, activator protein-1 transcription factor subunit (FOSL2), cyclin-dependent kinase inhibitor 1A (CDKN1A) and kinectin 1 (KTN1) genes were identified as key genes by using Cytoscape software. Functional enrichment revealed that the DEGs were mainly accumulated in the ErbB, MAPK and PI3K-Akt pathways. Reverse transcription-quantitative PCR analysis confirmed a significant reduction in the expression levels of FOSL2, CDKN1A and KTN1 in OA samples. These genes have the potential to become novel diagnostic and therapeutic targets for OA.

PMID:33732303 | PMC:PMC7903481 | DOI:10.3892/etm.2021.9761

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Upregulated expression of leukocyte immunoglobulin-like receptor A3 in patients with severe aplastic anemia

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Exp Ther Med. 2021 Apr;21(4):346. doi: 10.3892/etm.2021.9777. Epub 2021 Feb 11.

ABSTRACT

Severe aplastic anemia (SAA) is a rare and potentially life-threatening disease characterized by pancytopenia and bone marrow (BM) hypoplasia. In a previous study by our group, increased expression of leukocyte immunoglobulin-like receptors A (LILRA), LILRA3 in myeloid dendritic cells (mDCs) and LILRA5 in CD34+ cells in SAA was detected using proteomics techniques, highlighting their potential role in disease pathogenesis. In the present study, the expression of LILRA1-6 mRNA was assessed in the BM mononuclear cells of patients with SAA using reverse transcription-quantitative (RT-q)PCR. The expression of homogenic LILRA3 and LILRA5 isoform on mDCs, as well as CD34+, CD3+CD8+, CD19+ and CD14+ cells, was detected using flow cytometry. mDCs were then induced, cultured and sorted. The e xpression of LILRA3 was confirmed using RT-qPCR and western blot analyses. The serum levels of soluble LILRA3 were measured using ELISA. Furthermore, the relationship between LILRA3 expression and disease severity was assessed. The results indicated increased LILRA3 mRNA expression in patients with SAA. The percentage of LILRA3+ in BM mDCs and CD34+ cells was increased. Compared with controls, the relative LILRA3 mRNA expression and the relative protein intensity were highly increased in SAA mDCs. The serum LILRA3 levels in patients with SAA were also increased. The proportion of LILRA3+CD11C+ human leukocyte antigen (HLA)-DR+/CD11C+HLA-DR+ cells was positively correlated with the ratio of LILRA3+CD34+/CD34+ cells and the expression of LILRA3 mRNA. Taken together, the expression of LILRA3 on mDCs of patients with SAA was increased, which may affect the function of mDCs. LILR A3 may have a significant role in the immune pathogenesis of SAA.

PMID:33732319 | PMC:PMC7903422 | DOI:10.3892/etm.2021.9777

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The effect of the area proportion of the metastatic lesion within the central metastatic lymph node on response to therapy in papillary thyroid carcinoma

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Oncol Lett. 2021 Apr;21(4):284. doi: 10.3892/ol.2021.12545. Epub 2021 Feb 12.

ABSTRACT

Lymph node (LN) metastasis has been strongly associated with locoregional recurrence and decreased survival time of patients with papillary thyroid carcinoma (PTC). Although the characteristics of the metastatic LNs (mLN) have been determined, including size, number, micro-metastasis and extra-nodal extension (ENE), further analysis is warranted. The present study introduced a new parameter known as the area proportion of the metastatic lesion within the central mLNs (APmCLN). The objective was to evaluate the impact of the APmCLN on response to therapy in patients with PTC. In total, 355 patients with PTC treated with total thyroidectomy and neck dissection, post-operative radioactive iodine and thyroid-stimulating hormone suppression were retrospectively studied. The patients were classified into two groups: Group A (APmCLN ≤75%) and group B (APmCLN >75%). The association of various clinicopathological characteristics between these two groups was investigated. Univariate and multivariate analyses were used to evaluate risk factors associated with a non-Excellent response to therapy and recurrence-free survival (RFS). The analysis showed that APmCLN >75% was significantly associated with extra-thyroidal extension, clinically apparent nodes (cN1), pathological N1b (pN1b), ENE, greater number and larger size of central mLN and larger size of the central LN metastatic lesion. Furthermore, it was reported that chronic lymphocytic thyroiditis, larger central mLN size and APmCLN >75% were independent risk factors for a non-excellent response to therapy. Finally, it was determined that the rate of excellent response to therapy was significantly higher in pathological N1 (pN1) patients with APmCLN ≤75% (108/144, 75.0%) compared with patients with APmCLN >75% (27/47, 57.4%) (P=0.022). However, there was no significant difference (P=0.247) between patients with APmCLN ≤75% and pN0 (132/164, 80.5%). RFS was 89.4% in patients with pN1-APmCLN >75%, whereas those with pN1-APmCLN ≤75% and pN0 did not experience a relapse. Patients with PTC with APmCLN >75% should be regarded as high-risk and may require more aggressive treatment and careful follow-up.

PMID:33732360 | PMC:PMC7905529 | DOI:10.3892/ol.2021.12545

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Short-Term Voice Improvement after Repeated Office-Based Platelet-Rich Plasma PRP Injection in Patients with Vocal Fold Scar, Sulcus, and Atrophy

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Improving the voice of patients with vocal atrophy, scar, and sulcus vocalis remains challenging. Platelet-rich plasma (PRP) is an autologous biological suitable for regenerative medicine. Office-based injections of PRP may serve as a source of improved wound healing.
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