Αρχειοθήκη ιστολογίου

Τρίτη 9 Μαρτίου 2021

The protective mechanism of action of plantamajoside on a rat model of acute spinal cord injury

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Exp Ther Med. 2021 Apr;21(4):378. doi: 10.3892/etm.2021.9809. Epub 2021 Feb 19.

ABSTRACT

Acute spinal cord injury (ASCI) is a severe traumatic disease of the central nervous system, characterized by a high incidence and high morbidity, for which there are no effective drug therapies in the clinic. A rat model of ASCI was established to study the effects of plantamajoside (PMS) treatment on the expression of apoptotic factors, including caspase-3, caspase-9, poly (ADP-ribose) polymerase (PARP), Bax and Bcl-2. The Allen's weight hit rat ASCI model was used for the present study, and the rats were treated with various concentrations of PMS. The behavior of rats was assessed using the Basso-Beattle-Bresnahan locomotor rating scale (BBB), the histopathologic changes of spinal cord tissue were observed by hematoxylin and eosin staining, the survival of neurons was assessed by TUNEL staining and the expression levels of apoptotic proteins suc h as caspase-3, caspase-9, PARP, Bcl-2 and Bax was measured using western blot assays and RT-qPCR. It was observed that PMS could reverse the decrease in the BBB score after ASCI, improve the morphological characteristics of the spinal cord, reduce the degree apoptosis and affect the expression of caspase-3, caspase-9, PARP, Bax and Bcl-2 in a concentration dependent manner. In conclusion, PMS protected ASCI rats by inhibiting apoptosis; therefore PMS may be a potential candidate for ASCI therapy.

PMID:33680100 | PMC:PMC7918247 | DOI:10.3892/etm.2021.9809

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Prognostic value of miR-339-5p in patients with prostate cancer and its effects on tumor progression

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Exp Ther Med. 2021 Apr;21(4):390. doi: 10.3892/etm.2021.9821. Epub 2021 Feb 24.

ABSTRACT

Prostate cancer places a serious health burden on males. The present study aimed to explore the potential prognostic significance and biological function of microRNA (miR)-339-5p in patients with prostate cancer. The expression of miR-339-5p was detected in prostate cancer tissues and cell lines by using reverse transcription-quantitative PCR. Kaplan-Meier survival curves and Cox regression analyses were used to investigate the prognostic significance of miR-339-5p in prostate cancer. The Cell Counting Kit-8 assay was used to determine the effect of miR-339-5p on prostate cancer cell proliferation. Transwell assays were used to assess the effect of miR-339-5p on cell migration and invasion. The results indicated that the expression of miR-339-5p was downregulated in prostate cancer tissues and cell lines. Downregulation of miR-339-5p was significan tly associated with the Gleason score, lymph node metastasis and TNM stage. Patients with high miR-339-5p expression levels had a longer survival time than those with low expression levels. Multivariate Cox regression analysis indicated that miR-339-5p may be an independent prognostic factor for the overall survival of patients with prostate cancer. Overexpression of miR-339-5p inhibited the proliferation, migration and invasion of prostate cancer cells. Taken together, these results indicated that miR-339-5p functions as a suppressor gene in prostate cancer and acts by inhibiting cell proliferation, migration and invasion of prostate cancer cells. miR-339-5p may serve as an independent prognostic biomarker and therapeutic target for the treatment of prostate cancer.

PMID:33680112 | PMC:PMC7918444 | DOI:10.3892/etm.2021.9821

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Correlation between optic disc deformation and retinal vasculature in non-pathological high myopia

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Exp Ther Med. 2021 Apr;21(4):380. doi: 10.3892/etm.2021.9811. Epub 2021 Feb 19.

ABSTRACT

The aim of the current study was to investigate the correlation between optic disc deformation and retinal vasculature in high myopia. A total of 130 eyes with non-pathological high myopia were included in the current cross-sectional study. β-zone parapapillary atrophy (β-PPA), optic disc tilt ratio, and horizontal and vertical disc diameters were analyzed using fundus color photography. A 3x3 mm grid and a 4.5x4.5 mm grid were used to scan parafoveal and peripapillary regions, respectively, using optical coherence tomography angiography. Vessel flow density (VFD) and fractal dimension of the retina, as well as the foveal avascular zone (FAZ), were analyzed and quantified using en face projection images. Optic disc parameters that were associated with vascular changes were determined using multiple linear regression analysis. The results from the multivariate analysis revealed that β-PPA was negatively correlated with the VFD of the superficial retinal plexus (R=-2.805; P=0.006), deep retinal plexus (R=-2.801; P=0.006), radial parapapillary capillaries (R=-3.936; P<0.001) and enhanced-depth imaging of the fovea (R=-2.161; P=0.034). Additionally, FAZ was not significantly correlated with any factors in the current study. Age was negatively correlated with the VFD of the retina (R=-4.234; P<0.001), while the optic tilt ratio (R=-2.291; P=0.025) was negatively correlated with three sectors in the deep layer. Overall, the present results demonstrated that optic disc deformation was negatively correlated with the retinal microvasculature in non-pathological high myopia, particularly in the radial peripapillary capillaries and the deep retinal plexus. Therefore, optic disc deformation may be used to predict the retinal vasculature in high myopia.

PMID:33680102 | PMC:PMC7918286 | DOI:10.3892/etm.2021.9811

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Intestinal mucosal microbiota composition of patients with acquired immune deficiency syndrome in Guangzhou, China

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Exp Ther Med. 2021 Apr;21(4):391. doi: 10.3892/etm.2021.9822. Epub 2021 Feb 24.

ABSTRACT

Acquired immune deficiency syndrome, caused by the human immunodeficiency virus (HIV), has been associated with intestinal dysbiosis, which includes an increase in the number of mucosa-associated pathobionts. In the present study, the intestinal mucosal microbiota patterns of HIV-infected patients were compared with those of healthy individuals in a population from Guangzhou, China. The gut microbiota of intestinal mucosal samples from 12 patients with HIV (transmission routes included sex and intravenous drug abuse) was compared with that of 12 healthy age- and sex-matched controls. Gut microbial communities were profiled via sequencing of the bacterial 16S ribosomal RNA genes. Dysbiosis in HIV-infected individuals was characterized by decreased α-diversity, decreased levels of Firmicutes and increased levels of Proteobacteria. Furthermore, low m ean counts of Lachnoclostridium, Roseburia, Thauera, Dorea and Roseburia inulinivorans, and high mean counts of Halomonas and Shewanella bacteria, were indicated to be HIV-associated mucosal bacterial alterations. The relative abundance of Fusobacterium and Lachnoclostridium was significantly decreased, while that of Halomonas and Shewanella was significantly increased in patients with sexually transmitted HIV-infection compared with healthy controls. Alterations of the gut microbiota during HIV infection were also indicated to be associated with the route of HIV transmission. Certain bacteria may be potential biomarkers for HIV infection in patients from Guangzhou, China.

PMID:33680113 | PMC:PMC7918403 | DOI:10.3892/etm.2021.9822

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Efficacy and safety of the SGLT2 inhibitor dapagliflozin in type 1 diabetes: A meta-analysis of randomized controlled trials

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Exp Ther Med. 2021 Apr;21(4):382. doi: 10.3892/etm.2021.9813. Epub 2021 Feb 19.

ABSTRACT

Sodium glucose cotransporter-2 (SGLT2) is a sodium-dependent glucose transporter responsible for renal absorption of glucose. Dapagliflozin is an SGLT2 inhibitor used in patients with type 1 diabetes to promote urinary glucose excretion, but to date, randomized controlled trials (RCTs) to evaluate the effect of this drug in this disease have not been systematically evaluated. Therefore, the aim of the present study was to evaluate the efficacy and safety of dapagliflozin, as an adjuvant therapy to insulin, in the treatment of type 1 diabetes mellitus through a systematic review and meta-analysis. The Cochrane Library Database, Medline and Embase databases were used to search articles published between January 1st 2004 and February 5th 2020 with no language restrictions relating to RCTs. After extracting the data, the quality of the RCTs was evaluat ed and the data were statistically analyzed. A total of 4 RCTs with 1,691 participants were included. Dapagliflozin resulted in decreased glycosylated hemoglobin A1c (0.40-0.45%), body weight (2.52-3.85 kg), mean daily glucose (0.76-0.99 mmol/l) and mean amplitude of glucose excursion (0.54-1.07 mmol/l; all with P<0.00001) compared to placebo. Subgroup analysis by dose indicated no significant difference in all efficacy outcome indicators between dapagliflozin at 5 and at 10 mg (P>0.1). Compared with placebo, the use of dapagliflozin in patients with type 1 diabetes increased the risk of adverse events and serious adverse events (P<0.05), but did not increase the risks of infection, diabetic ketoacidosis (DKA) and discontinuation due to adverse events. Analysis by dose group suggested that no significant difference in all safety outcome indicators between dapagliflozin at 5 and at 10 mg (P>0.1). In conclusion, dapagliflozin had a significant effect on type 1 diabetes. Ho wever, the use of dapagliflozin significantly increased the incidence of adverse events and serious adverse events compared with placebo. Dapagliflozin-assisted short-term (24 weeks) insulin therapy for type 1 diabetes did not increase the risk of DKA but additional high-quality studies are required to determine its long-term efficacy and safety.

PMID:33680104 | PMC:PMC7918543 | DOI:10.3892/etm.2021.9813

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Successful recovery of a patient with multiple myeloma from severe coronavirus disease 2019 (COVID-19) pneumonia during the first chemotherapy cycle: A case report

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Exp Ther Med. 2021 Apr;21(4):392. doi: 10.3892/etm.2021.9823. Epub 2021 Feb 24.

ABSTRACT

A continuing outbreak of pneumonia associated with the 2019 novel coronavirus (2019-nCoV) was initially described in Wuhan, China in December 2019. Weak and elderly individuals, and those with chronic diseases such as hematological malignancies are prone to develop severe pneumonia. The humoral immunity of patients with multiple myeloma is prevalently low, and their inferior immunity further deteriorates during chemotherapy. For patients with onco-hematological malignancies infected with 2019-nCoV during the first chemotherapy cycle, the clinical treatment experience is lacking. The present study is a report of a 61-year-old patient newly diagnosed with multiple myeloma in the key 2019-nCoV outbreak area, who suffered severe 2019-nCoV pneumonia during the first chemotherapy cycle. The present case report demonstrated that a rapidly progressive and severe form of pneumonia was a specific clinical feature of COVID-19, especially in immunocompromised patients with cancer. The treatment strategy combining timely suspending chemotherapy, early intervention using intravenous immunoglobulin, interferon α inhalation and oral antiviral drugs was effective. Therefore, in the pandemic environment, it is strongly recommend that the risk of 2019-nCoV infection is assessed prior to chemotherapy.

PMID:33680114 | PMC:PMC7918348 | DOI:10.3892/etm.2021.9823

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MicroRNA-497-5p downregulation inhibits cell viability, reduces extracellular matrix deposition and induces apoptosis in human hyperplastic scar fibroblasts by regulating Smad7

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Exp Ther Med. 2021 Apr;21(4):384. doi: 10.3892/etm.2021.9815. Epub 2021 Feb 23.

ABSTRACT

Hypertrophic scars (HSs) are characterized by excessive extracellular matrix deposition and excessive growth of dense fibrous tissues. MicroRNAs (miRNAs/miRs) serve key roles in HS formation. The present study investigated the expression, role and mechanism underlying the effects of miR-497-5p in HS formation. miR-497-5p expression was detected via reverse transcription-quantitative PCR. The association between miR-497-5p and Smad7 was analyzed using TargetScan and luciferase reporter assays. Protein expression levels of extracellular matrix markers were measured via western blotting. Cell viability and apoptosis were determined using the Cell Counting Kit-8 assay and flow cytometry, respectively. The results suggested that miR-497-5p expression was upregulated in HS tissues and human HS fibroblasts (hHSFs) compared with healthy control skin tissue s and CCC-ESF-1 cells, respectively. Smad7 was directly targeted by miR-497-5p, and was downregulated in HS tissues and hHSFs compared with healthy control skin tissues and CCC-ESF-1 cells, respectively. Moreover, Smad7 upregulation significantly inhibited cell viability, decreased extracellular matrix deposition and induced apoptosis in hHSFs compared with the control-plasmid group. Moreover, the results indicated that, compared with the inhibitor control group, miR-497-5p inhibitor inhibited cell viability, decreased extracellular matrix deposition and induced apoptosis in hHSFs, which were significantly reversed by Smad7 knockdown. In conclusion, the results indicated that miR-497-5p downregulation repressed HS formation by inhibiting extracellular matrix deposition and hHSF proliferation at least partly by targeting Smad7.

PMID:33680106 | PMC:PMC7918061 | DOI:10.3892/etm.2021.9815

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Epalrestat suppresses cadmium-induced cytotoxicity through Nrf2 in endothelial cells

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Exp Ther Med. 2021 Apr;21(4):393. doi: 10.3892/etm.2021.9824. Epub 2021 Feb 24.

ABSTRACT

Cadmium (Cd) is an industrial and environmental pollutant that targets the vascular endothelium. The vascular system is critically affected by Cd toxicity. Recent studies have indicated an association between Cd and vascular diseases, although the mechanisms of Cd implications in vascular diseases are not clear. The purpose of the present study was to determine whether epalrestat (EPS), which is used for the treatment of diabetic neuropathy, protects against Cd-induced cytotoxicity in bovine aortic endothelial cells (BAECs). In the present study, the effects of EPS at near-plasma concentration were examined on Cd-induced cytotoxicity in BAECs. Cd-induced cytotoxicity was suppressed by pretreatment with EPS. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a key transcription factor that serves a role in regulating the expression of glutamate c ysteine ligase, the rate-limiting enzyme in glutathione (GSH) synthesis. In a previous study, EPS was demonstrated to increase GSH levels in BAECs in association with the Nrf2 pathway. In the present study, EPS increased GSH levels in BAECs exposed to Cd. The protective ability of EPS against the Cd-induced cytotoxicity disappeared following Nrf2 small interfering RNA transfection. In addition, EPS affected the intracellular levels of Cd, Cd transporter ZIP8 and metallothionein. To the best of our knowledge, the current study demonstrated, for the first time, that EPS suppresses Cd-induced cytotoxicity in BAECs. The upregulation of GSH may be associated with the suppression of Cd-induced cytotoxicity by EPS. From these findings, it may be proposed that the regulation of GSH, ZIP8 and metallothionein by EPS is a promising therapeutic approach to prevent Cd-induced toxicity.

PMID:33680115 | PMC:PMC7918249 | DOI:10.3892/etm.2021.9824

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Meta-analysis of the diagnostic value of serum, plasma and urine neutrophil gelatinase-associated lipocalin for the detection of acute kidney injury in patients with sepsis

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Exp Ther Med. 2021 Apr;21(4):386. doi: 10.3892/etm.2021.9817. Epub 2021 Feb 23.

ABSTRACT

The objective of the present study was to assess the diagnostic value of urine, serum and plasma neutrophil gelatinase-associated lipocalin (NGAL) for the early diagnosis of acute kidney injury (AKI) among patients with suspected sepsis. Therefore, a meta-analysis was carried out to evaluate diagnostic accuracy data from the literature regarding the diagnosis of AKI in patients with sepsis. Electronic databases were systematically searched for relevant studies and quality assessment was conducted using the Quality Assessment for Diagnostic Accuracy Studies 2 tool. A summary receiver operating characteristic curve analysis was performed, and several parameters including sensitivity, specificity, diagnosis odds ratio (DOR) and area under the curve (AUC) were calculated to evaluate the diagnostic performance of urine, serum and plasma NGAL. Meta-regre ssion, sensitivity and subgroup analysis were also conducted to identify the source of heterogeneity in the eligible studies. In total, 28 studies were included. The pooled sensitivities for urine, serum and plasma NGAL were 0.87, 0.83 and 0.80, respectively. Pooled specificity was 0.84, 0.79 and 0.74. The DORs were 35, 18 and 11, respectively. The AUC for urine, serum and plasma NGAL were 0.92, 0.87 and 0.84, respectively. Urine NGAL presented superior performance for the diagnosis of AKI with the highest AUC and other diagnostic accuracy values, compared with serum and plasma NGAL. Further studies are needed to clarify the controversial issue between the usefulness of serum and plasma NGAL.

PMID:33680108 | PMC :PMC7918111 | DOI:10.3892/etm.2021.9817

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Cervical malignant mixed mesonephric tumour: A case report with local recurrence after six-years and next-generation sequencing analysis with particular reference to the ataxia telangiectasia mutated gene

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Exp Ther Med. 2021 Apr;21(4):394. doi: 10.3892/etm.2021.9825. Epub 2021 Feb 24.

ABSTRACT

Malignant mixed mesonephric tumours (MMMsT) of the female genital tract are extremely rare, and the majority are located in the wall of the cervix uteri. At present, there are no reports of the molecular characterisation of MMMsT of the female genital tract. Herein, we report the morphological, immunohistochemical and molecular features of this rare malignancy using next-generation sequencing (NGS) analysis. A 58-year-old woman presented with vaginal bleeding. In 2013, she had been diagnosed with a cervical carcinosarcoma of probable mesonephric origin and International Federation of Gynaecology and Obstetrics (FIGO) stage IB that had been treated by total hysterosalpingo-oopherectomy without adjuvant chemo-radiotherapy. Ultrasonography showed a vaginal mass measuring 25 mm in the maximum dimension. Biopsy was performed and showed a biphasic neopla sm composed of adenocarcinoma and sarcoma. Immunohistochemistry showed positive staining for epithelial membrane antigen (EMA), pancytokeratin (MNF116), paired box 8 (PAX-8), β-catenin, cytokeratin 7, cyclin D1, GATA3 and CD10. Androgen receptor positivity was detected in very limited areas. Cytokeratin 20, carcinoembryonic antigen (CEA), oestrogen receptor (ER), progesterone receptor (PR), transcription termination factor 1 (TTF1), Wilm's tumour antigen-1 (WT-1), calretinin and p16 were negative. The immunohistochemical profile was consistent with mesonephric origin. NGS analysis identified a variant of the ataxia-telangiectasia mutated (ATM) gene (p.Phe858Leu; c.2572 T>C; COSM21826). The number of detected allele frequency reads of ATM mutation following clinical relapse was higher, compared to its baseline: 65 vs. 96%. The differential diagnosis of MMMsT includes mesonephric hyperplasia, malignant mixed Mullerian tumour (carcinosarcoma), endometrioid adenocarcin oma and endometrial stromal sarcoma. The clinical significance of the observed ATM variant in the case reported herein is unknown. The present findings need further verification, as the mutation in ATM may result in chemotherapy resistance or conversely, may be exploited for targeted therapies.

PMID:33680116 | PMC:PMC7918045 | DOI:10.3892/etm.2021.9825

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