Τετάρτη 26 Μαΐου 2021

Potential protective effect of hesperidin on hypoxia/reoxygenation-induced hepatocyte injury

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Exp Ther Med. 2021 Jul;22(1):764. doi: 10.3892/etm.2021.10196. Epub 2021 May 13.

ABSTRACT

Hesperidin (HDN) has been reported to have hydrogen radical- and hydrogen peroxide-removal activities and to serve an antioxidant role in biological systems. However, whether HDN protects hepatocytes (HCs) against hypoxia/reoxygenation (H/R)-induced injury remains unknown. The present study aimed to explore the role of HDN in H/R-induced injury. HCs were isolated and cultured under H/R conditions with or without HDN treatment. HC damage was markedly induced under H/R, as indicated by cell viability, supernatant lactate dehydrogenase levels and alanine aminotransferase levels; however, HDN treatment significantly reversed HC injury. Oxidative stress markers (malondialdehyde, superoxide dismutase, glutathioneand reactive oxygen species) were increased markedly during H/R in HCs; however, this effect was significantly attenuated after exposure to HDN . Compared with those of the control group, the mRNA expression levels of IL-6 and TNF-α in HCs and the concentrations of IL-6 and TNF-α in the supernatants increased significantly following H/R, and HDN significantly ameliorated these effects. Western blotting demonstrated that microtubule-associated protein 1 light chain 3α (MAP1LC3A, also known as LC3) and Beclin-1 protein expression levels increased, while sequestosome 1 levels decreased during H/R following exposure to HDN. The number of GFP-LC3 puncta in HCs following exposure to HDN was increased compared with that observed in HCs without HDN exposure under the H/R conditions after bafilomycin A1 treatment. In summary, the present study demonstrated that HDN attenuated HC oxidative stress and inflammatory responses while enhancing autophagy during H/R. HDN may have a potential protective effect on HCs during H/R-induced injury.

PMID:34035861 | PMC:PMC8135133 | DOI:10.3892/etm.2021.10196

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Dynamics of serum α-fetoprotein in viral hepatitis C without hepatocellular carcinoma

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Exp Ther Med. 2021 Jul;22(1):749. doi: 10.3892/etm.2021.10181. Epub 2021 May 12.

ABSTRACT

Viral hepatitis C represents a significant liver pathology worldwide, with a detrimental impact on national health systems. The present study aimed to correlate the levels of serum α-fetoprotein (AFP) with prognostic tools such as Fibroscan®, the presence of mixed cryoglobulinemia, and various demographic and standard biochemical markers, in patients with chronic hepatitis C, unrelated to hepatocellular carcinoma (HCC). A clinical study was designed considering three study groups: Hepatitis C virus (HCV) group including 35 patients with chronic hepatitis C and detectible viral load; sustained viral response (SVR) group including 20 HCV patients without detectable virus load 12 weeks after therapy cessation; a control group represented by 37 healthy volunteers. It was observed that serum AFP was moderately increased in the HCV and SVR groups and was positively correlated with aspartate transaminase (AST), alkaline phosphatase (AP), and γ-glutamyl transferase (GGT). The incidence of mixed cryoglobulinemia was increased in the HCV group, and the degree of fibrosis assessed by Fibroscan® was increased in both the HCV and SVR groups. In conclusion, the data revealed that a moderate increase in AFP levels could be present in patients with HCV even in the absence of HCC, unrelated to viral load or therapy response and that there was a linear positive correlation between serum levels of AFP and the degree of hepatic cytolysis and cholestasis. Additionally, mixed cryoglobulinemia was present in HCV patients with patent viral load, decreasing in those with SVR after therapy cessation unrelated to any renal impairment, while the degree of fibrosis was increased in HCV-infected patients, with no reversibility 12 weeks after successful therapy.

PMID:34035846 | PMC:PMC8135122 | DOI:10.3892/etm.2021.10181

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Effects of withdrawing an atherogenic diet on the atherosclerotic plaque in rabbits

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Exp Ther Med. 2021 Jul;22(1):751. doi: 10.3892/etm.2021.10183. Epub 2021 May 12.

ABSTRACT

Lifestyle interventions and pharmacotherapy are the most common of non-invasive treatments for atherosclerosis, but the individual effect of diet on plaques remains unclear. The current study aimed to investigate the effect of withdrawing the atherogenic diet on plaque in the aortas of rabbits. Experimental atheroma was induced in 33 rabbits using a 1% high cholesterol diet for 30 days (H-30 d) or 90 days (H-90 d, baseline group). After 90 days of the atherogenic diet, the remaining animals were divided into four groups: A total of 10 rabbits continued to consume the atherogenic diet for 50 days (H-90 d & H-50 d; n=5) or 140 days (H-90 d & H-140 d; n=5). Another 13 rabbits were switched to a chow diet for 50 days (H-90 d & C-50 d; n=7) or 140 days (H-90 d & C-140 d; n=6). A total of 10 age-matched rabbits in the control groups were fed a chow diet for 90 and 230 days, respectively. The en face or cross-sectional plaque areas were determined using oil red O staining and elastic van Gieson staining. Immunohistochemistry analyses were used to assess the macrophages or smooth muscle cell contents. When fed an atherogenic diet for 90 days, the rabbits' abdominal aortas exhibited severe atherosclerotic lesions (the median en face plaque area was 63.6%). After withdrawing the atherogenic diet, the plaque area did not shrink with feeding the chow diet compared with the baseline, but increased to 71.8 or 80.5% after 50 or 140 days, respectively. After removing cholesterol from the diet, the lipids content in the plaques increased during the first 50 days, and then decreased compared with the baseline group. Furthermore, withdrawing the atherogenic diet increased the total collagen content and the percentage of the smooth muscle cells, alleviated macrophage infiltration, decreased the vulnerable index and promoted the cross-linking of collagen. Feeding the rabbits an atherogenic diet followed by removal of cholesterol from the diet did not lead to the regression of established lesions but instead delayed the progression of the lesions and promoted the stabilization of the plaque.

PMID:34035848 | PMC:PMC8135140 | DOI:10.3892/e tm.2021.10183

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Clinical and therapeutic features of acute cholecystitis in diabetic patients

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Exp Ther Med. 2021 Jul;22(1):758. doi: 10.3892/etm.2021.10190. Epub 2021 May 13.

ABSTRACT

The present study aimed to compare the clinical, paraclinical, intraoperative findings, and postoperative complications in acute cholecystitis in diabetic patients vs. non-diabetic patients. A 2-year retrospective study was performed on the patients who underwent emergency cholecystectomy for acute cholecystitis between 2017 and 2019 at the 4th Department of Surgery, Emergency University Hospital Bucharest. The diabetic subgroup numbered 46 eligible patients and the non-diabetic one 287 patients. Demographics, the severity of the clinical forms, biological variables (including white cell count, urea, creatinine, coagulation and liver function tests) comorbidity status, surgical approach, postoperative complications, and hospital stay were analyzed. Statistical analyses were performed to assess comparative results between the aforementioned data (S PSS V 13.0). The CCI and ASA risk classes were increased in the diabetic group, with 34.78% of patients having 3 or more associated comorbidities. No statistically significant associations were demonstrated between diabetes and the severity of the cholecystitis and risk for conversion. Postoperatively both minor complications such as surgical site infections and major cardiovascular events were more common in the diabetic subgroup (P=0.0254), well associated with the preoperative status and baseline cardiovascular comorbidities. Laparoscopic cholecystectomy is a safe procedure for diabetic patients, which can provide the best outcomes, by decreasing the risks of surgical wounds. Attentive perioperative care and good glycemic control must be provided to minimize the risk of complications.

PMID:34035855 | PMC:PMC8135114 | DOI:10.3892/etm.2021.10190

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Clinical application of whole-exome sequencing: A retrospective, single-center study

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Exp Ther Med. 2021 Jul;22(1):753. doi: 10.3892/etm.2021.10185. Epub 2021 May 12.

ABSTRACT

The aim of the present study was to assess the practical diagnostic value of whole-exome sequencing (WES) in patients with different phenotypes and to explore possible strategies to increase the capability of WES in identifying disease-causing genes. A total of 1,360 patients (aged from 1 day to 42 years old) with manifestations of genetic diseases were genotyped using WES and statistical analysis was performed on the results obtained. Within this cohort, the overall positive rate of identification of a disease-causing gene alteration was 44.41%. The positive identification rate where trio-samples were used (from the proband and both parents) was higher than that where a single proband sample was used (50.00 vs. 43.71%), and 604 positive cases with 150 genetic syndromes, 510 genes and 718 mutations were detected. Missense mutations were the most c ommon variations (n=335, 45.27%) and visual or auditory abnormalities (58.51%) had the highest rate of association with a genetic abnormality. The positive detection rate of WES was elevated with the increase in the number of clinical symptoms from 1 to 8. The present study indicated that WES may be used as a valuable tool in the clinic and the positive rate depends more on the professional experience of clinicians rather than on the analytical capabilities of the data analyst. At the same time, particular attention must be paid to certain possible factors (such as the age of the patients as well as possible exon deletions), which may affect the diagnostic rate while applying this process.

PMID:34035850 | PMC:PMC8135134 | DOI:10.3892/etm.2021.10185

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Portal vein thrombosis: A concise review (Review)

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Exp Ther Med. 2021 Jul;22(1):759. doi: 10.3892/etm.2021.10191. Epub 2021 May 13.

ABSTRACT

Portal vein thrombosis (PVT) is a frequent complication in cirrhotic patients, but it may also exist as a basic vascular condition even without any liver damage. Local and systemic factors play a significant role in the pathogenesis of PVT; yet, in practice, more than one factor may be identified. PVT can be considered a result of liver fibrosis and hepatic insufficiency. The JAK2 mutation has been accepted as a factor producing PVT. In general, the anticoagulants are recommended but this therapy should be used carefully in treating patients that associate coagulopathy or thrombocytopenia and esophageal varices. Acute PVT without bowel infarction has a good prognosis. In liver cirrhosis, the mortality due to hemorrhage is higher than in chronic PVT. Therefore, for the patients with PVT, the survival rate is decreased by 55% in two years, du e to hepatic insufficiency. Regarding the treatment, LMWH (low molecular weight heparine) is the most utilized in patients with cirrhosis, non-malignancies, infections, or those who are awaiting a liver transplant. DOACs (direct-acting oral anticoagulants) may be used in the rest of the medical conditions, being safe and equal to LMWH.

PMID:34035856 | PMC:PMC8135136 | DOI:10.3892/etm.2021.10191

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Long non-coding RNA DUXAP8 promotes tumorigenesis by regulating IGF1R via miR-9-3p in hepatocellular carcinoma

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Exp Ther Med. 2021 Jul;22(1):755. doi: 10.3892/etm.2021.10187. Epub 2021 May 12.

ABSTRACT

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide with a low 5-year survival rate. Long non-coding RNA (lncRNA) double homeobox A pseudogene 8 (DUXAP8) is an oncogene and a potential biomarker in various tumors, such as ovarian, colorectal and non-small-cell lung cancer. However, the function and molecular mechanism underlying DUXAP8 in HCC progression is not completely understood. The expression of DUXAP8, microRNA (miR)-9-3p and insulin-like growth factor 1 receptor (IGF1R) in HCC tissues and cells was detected via reverse transcription-quantitative PCR. The expression levels of IGF1R and epithelial-mesenchymal transition-associated proteins (Snail, Slug, E-cadherin, N-cadherin and vimentin) were assessed via western blotting. The effects of DUXAP8, miR-9-3p and IGF1R on proliferation, migration and inva sion were examined by conducting Cell Counting Kit-8 and Transwell assays, respectively. The interaction between miR-9-3p and DUXAP8 or IGF1R was predicted using StarBase or TargetScan, and further assessed using dual luciferase reporter and RNA immunoprecipitation assays. DUXAP8 and IGF1R were upregulated and miR-9-3p was downregulated in HCC tissues and cells compared with adjacent healthy tissues and a normal liver cell line, respectively. miR-9-3p overexpression decreased the protein expression level of IGF1R, and miR-9-3p knockdown enhanced the protein expression level of IGF1R in HCC cells compared with the corresponding control groups. Moreover, compared with the corresponding control groups, DUXAP8 knockdown and miR-9-3p overexpression increased E-cadherin protein expression levels, and decreased Snail, Slug, N-cadherin and vimentin protein expression levels. However, miR-9-3p inhibitor and IGF1R overexpression reversed DUXAP8 knockdown- and miR-9-3p overexpression-induced e ffects, respectively. In addition, compared with the corresponding control groups, DUXAP8 knockdown and miR-9-3p overexpression suppressed proliferation, migration and invasion, which was reversed by miR-9-3p inhibitor and IGF1R overexpression, respectively. Moreover, miR-9-3p as the target of DUXAP8 and IGF1R as the target of miR-9-3p were verified in HCC cells. lncRNA DUXAP8 contributed to HCC tumorigenesis via the miR-9-3p/IGF1R axis, providing a novel therapeutic approach for HCC diagnosis and treatment.

PMID:34035852 | PMC:PMC8135127 | DOI:10.3892/etm.2021.10187

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Clinical, biological and electroencephalographic monitoring of newborns with neurological risk in the Neonatal Intensive Care Unit

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Exp Ther Med. 2021 Jul;22(1):760. doi: 10.3892/etm.2021.10192. Epub 2021 May 13.

ABSTRACT

Newborns admitted to the Neonatal Intensive Care Unit (NICU) require increased attention regarding neurological assessment and monitoring, due to immaturity or certain conditions that occur during the perinatal and neonatal period. Hypoxic-ischemic encephalopathy (HIE) following perinatal asphyxia is one of the most studied clinical conditions due to the risk of medium- and long-term neurobehavioral outcome. We studied 43 newborns with HIE, for all 3 degrees of impairment, performed amplitude-integrated electroencephalography (aEEG) in the first hours of life and collected common laboratory tests, following serum glycemia at admission and creatinine, creatine kinase (CK) and lactate dehydrogenase (LDH) at admission and in the 3rd day of life. Newborns with mild HIE presented normal aEEG pattern and slightly elevated CK. A total of 80.9% of the newborns with moderate HIE had seizure patterns in aEEG, while among those with severe HIE, 71.4% had seizure patterns in aEEG and 28.5% burst suppression. CK and LDH were mean elevated in those with moderate HIE, and the newborns with severe HIE had also high creatinine values at admission and in the 3rd day of life. Statistically significant differences between the 3 degrees of HIE were noted in terms of creatinine (P=0.009) and CK (P=0.008) at admission and LDH in the 3rd day of life (P=0.036). Hypoglycemia was common in our study group. In conclusion, common blood tests in association with aEEG monitoring and rigorous neurological assessment can predict short-term outcome of HIE and multiorgan dysfunction and can help clinicians predict even long-term outcomes in severe HIE.

PMID:34035857 | PMC:PMC8135117 | DOI:10.3892/etm.2021.10192

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Predictive factors of 30-day mortality in patients with traumatic subdural hematoma

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Exp Ther Med. 2021 Jul;22(1):757. doi: 10.3892/etm.2021.10189. Epub 2021 May 13.

ABSTRACT

In the present study, we aimed to assess and analyze the predictive factors of 30-day mortality in patients with acute subdural hematoma (ASDH) who underwent surgical intervention after traumatic brain injury (TBI). We conducted a retrospective study, which included a cohort of 135 consecutive patients diagnosed with ASDH who required surgical evacuation. We assessed the demographic and clinical data, the imaging data of the hematoma described by preoperative computed tomography (CT) and the type of neurosurgical intervention for hematoma evacuation via either craniectomy or craniotomy. The patients were followed up for 30 days after head trauma and the occurrence of death was noted. Death was recorded in 63 (46.6%) patients at 30 days after TBI. There was a significant number of deceased patients who underwent craniectomy (71.4%). The Glasgow Com a Scale (GCS) was statistically significantly lower in patients who died (P<0.001), with a cut-off value of ≤12, under which the probability of death increased [AUC 0.830 (95% CI, 0.756-0.889); Se 90.48% (95% CI, 80.4-96.4); Sp 66.7% (95% CI, 54.6-77.3); P<0.001]. The midline shift was statistically significantly higher in deceased patients (P=0.005), with a cut-off value of >7 mm, over which the probability of death increased [AUC 0.637 (95% CI, 0.550-0.718); Se 38.1% (95% CI, 26.1-51.2); Sp 86.1% (95% CI, 75.9-93.1); P=0.003]. There were significantly more deceased patients with intracranial hypertension, brain herniation, brain swelling, intraparenchymal hematoma and cranial fracture. In multivariate analysis only a Glasgow score ≤12 and a midline shift >7 mm were independently linked to mortality. Brain herniation and intraparenchymal hematoma were associated with a higher probability of dying, but the statistical threshold was slightly exceeded. The type of neur osurgery performed for patients with ASDH was not an independent predictive factor for 30-day mortality. However, craniectomy was associated with a higher mortality in patients with ASDH.

PMID:34035854 | PMC:PMC8135115 | DOI:10.3892/etm.2021.10189

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circSKIL promotes the ossification of cervical posterior longitudinal ligament by activating the JNK/STAT3 pathway

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Exp Ther Med. 2021 Jul;22(1):761. doi: 10.3892/etm.2021.10193. Epub 2021 May 13.

ABSTRACT

Ossification of the posterior longitudinal ligament (OPLL) is a hyperostotic spinal condition that involves genetic factors as well as non-genetic factors, and its underlying molecular mechanism is largely unknown. Recently, circular RNAs (circRNAs) have been attracting the attention of researchers since they have important regulatory roles in many diseases, including bone metabolism disorders. The present study aimed to investigate the role of circRNA SKI-like proto-oncogene (circSKIL) in OPLL disease progression. First, primary posterior longitudinal ligament cells from patients with cervical spondylotic myelopathy (CSM) without OPLL (control group) and CSM patients with OPLL (OPLL group) were isolated, and the expression levels of circSKIL in ligament cells was found to be significantly increased in the OPLL group compared with control. This re sult was also confirmed in OPLL tissues. Next, circSKIL was overexpressed in control ligament cells, and the proliferation, mineralization, and osteogenic differentiation of ligament cells were found to be significantly enhanced; the phosphorylation levels of both JNK and STAT3 were upregulated. By contrast, the knockdown of circSKIL in OPLL ligament cells inhibited proliferation, mineralization, and osteogenic differentiation and inactivated the JNK/STAT3 pathway. Therefore, circSKIL may have a significant role in osteogenic differentiation and could serve as a potential target to prevent OPLL progression.

PMID:34035858 | PMC:PMC8135123 | DOI:10.3892/etm.2021.10193

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