Τετάρτη 26 Μαΐου 2021

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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RPLP1 is highly expressed in hepatocellular carcinoma tissues and promotes proliferation, invasion and migration of human hepatocellular carcinoma Hep3b cells

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Exp Ther Med. 2021 Jul;22(1):752. doi: 10.3892/etm.2021.10184. Epub 2021 May 12.

ABSTRACT

Hepatocellular carcinoma (HCC) is a common primary malignant tumor with a high mortality rate. Increasing evidence suggests that ribosomal protein LP1 (RPLP1) is involved in the progression of different types of cancer. Thus, the present study aimed to investigate the underlying molecular mechanism of RPLP1 in HCC progression. The cellular behaviors of Hep3b cells were assessed via Cell Counting Kit-8, colony formation, wound healing and Transwell assays. Western blot analysis was performed to detect protein expression levels, while reverse transcription-quantitative PCR analysis was performed to detect mRNA expression levels. The results demonstrated that RPLP1 was highly expressed in HCC tissues and cells, and the overexpression of RPLP1 was associated with a less favorable prognosis of patients with HCC. Notably, downregulation of RPLP1 signifi cantly suppressed the proliferation, migration and invasion of Hep3b cells. Taken together, the results of the present study suggested that RPLP1 acts as an oncogene in HCC, and thus may be used to treat patients with HCC.

PMID:34035849 | PMC:PMC8135124 | DOI:10.3892/etm.2021.10184

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Role of bone morphogenic protein-4 in gestational diabetes mellitus-related hypertension

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Exp Ther Med. 2021 Jul;22(1):762. doi: 10.3892/etm.2021.10194. Epub 2021 May 13.

ABSTRACT

Hyperglycaemia stimulates the synthesis and release of bone morphogenetic protein-4 (BMP-4) in vascular endothelial cells, which further induces peroxide production and inflammatory responses, leading to vascular endothelial dysfunction. However, the role of BMP-4 in gestational diabetes mellitus (GDM)-related vascular endothelial dysfunction remains unclear. In the present study, the hypothesis that the overexpression of BMP-4 would induce GDM-related hypertension by impairing vascular endothelial function was evaluated. An animal model of GDM was established in Sprague-Dawley (SD) rats. Based on blood pressure, rats were divided into control, GDM and GDM + hypertension (HT) groups. The expression levels of BMP-4, cyclooxygenase-2 (COX-2), nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 1 (NOX-1) and vascular cell adhesion molecule 1 (VCAM-1) in the endothelium of the abdominal aorta of rats in each group were determined via immunohistochemistry and western blotting. Pregnant SD rats were divided into four groups, separately infused with BMP-4, BMP-4 + noggin, noggin or vehicle by osmotic pumps, and blood pressure and vasorelaxation were examined. Immunohistochemistry indicated that the expression levels of the four proteins were lower in the control group than in the GDM and GDM + HT groups. The positive expression rate of VCAM-1 was significantly lower in the control group than in the GDM and GDM+HT groups, and the differences were statistically significant (χ2=17.325, P<0.05; χ2=10.080, P<0.05). Western blotting revealed that the expression level of the COX-2 protein exhibited a sequential increase in the three groups. The expression level of COX-2 in the control and GDM groups was significantly lower than that in the GDM+HT group (3.358±1.286; P<0.05 and P<0.05, respectiv ely). The expression level of VCAM-1 protein in the three groups also exhibited a significant sequential increase (F=31.732; P≤0.001). The expression level of VCAM-1 in the control and GDM groups was significantly lower than that in the GDM+HT group (2.698±0.223; P≤0.001 and P≤0.001, respectively). Infusion of BMP-4 increased systolic blood pressure (from 82 to 112 mmHg) and impaired vasorelaxation in pregnant SD rats after 2 weeks. Co-treatment with noggin completely blocked BMP-4-induced effects. Thus, the BMP-4/NOX-1/COX-2 signalling pathway may be involved in GDM-related hypertension, but VCAM-1 may be substantially associated with GDM-related hypertension. Furthermore, overexpression of BMP-4 could lead to hypertension by impairing endothelial function in pregnancy.

PMID:34035859 | PMC:PMC8135139 | DOI:10.3892/etm.2021.10194

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COVID-19-related thyroid conditions (Review)

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Exp Ther Med. 2021 Jul;22(1):756. doi: 10.3892/etm.2021.10188. Epub 2021 May 13.

ABSTRACT

In patients who were not previously diagnosed with any thyroid conditions, the scenario of COVID-19-related anomalies of the hypothalamus-pituitary-thyroid axes may include either: A process of central thyroid stimulating hormone (TSH) disturbances via virus-related hypophysitis; an atypical type of subacute thyroiditis which is connected to the virus spread or to excessive cytokine production including a destructive process with irreversible damage of the gland or low T3 (triiodothyronine) syndrome (so called non-thyroid illness syndrome) which is not specifically related to the COVID-19 infection, but which is associated with a very severe illness status. Our objective here was to briefly review thyroid changes due to the COVID-19 infection. Ongoing assessment of the effects of the COVID-19 pandemic will reveal more information on coronavirus-in duced thyroid conditions. Routine thyroid assays performed in patients with severe infection/at acute phase of COVID-19 are encouraged in order to detect thyrotoxicosis. After recovery, thyroid function should be assessed to identify potential hypothyroidism. There remain unanswered questions related to the prognostic value of interleukin-6 in infected patients, especially in cases with cytokine storm, and the necessity of thyroid hormone replacement in subjects with hypophysitis-related central hypothyroidism.

PMID:34035853 | PMC:PMC8135141 | DOI:10.3892/etm.2021.10188

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Septin 4 activates PPARγ/LXRα signaling by upregulating ABCA1 and ABCG1 expression to inhibit the formation of THP-1 macrophage-derived foam cells

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Exp Ther Med. 2021 Jul;22(1):763. doi: 10.3892/etm.2021.10195. Epub 2021 May 13.

ABSTRACT

Septin 4 is a member of a family of GTP-binding proteins that has been previously reported regulate cytoskeletal organization. In addition, it has been suggested to serve a role in atherosclerosis. Therefore, the present study aimed to investigate the effects of Septin 4 on foam cell formation. THP-1 cells were first exposed to phorbol-12-myristate-13-acetate for differentiation into macrophages before being transformed into foam cells by treatment with oxidized low-density lipoprotein (ox-LDL). Septin 4 expression was then knocked down or overexpressed in THP-1 cells using transfection, whilst peroxisome proliferator activated receptor γ (PPARγ) was also inhibited using its selective antagonist (T0070907) in the presence of Septin 4 overexpression. Oil red staining was used to detect lipid uptake, and total cholesterol (TC), free cholesterol (F C) and ATP binding cassette subfamily A/G member 1 (ABCA1/G1) protein expression were also measured. The results demonstrated that upon ox-LDL stimulation, macrophages that were derived from THP-1 cells transformed into foam cells, where Septin 4 was highly expressed in ox-LDL-induced foam cells. Septin 4 knockdown promoted TC and FC levels, but reduced ABCA1/G1 protein expression. The protein expression levels of PPARγ and liver X receptor α (LXRα) were also decreased after Septin 4 knockdown. However, Septin 4 overexpression resulted in the opposite results being observed. Additionally, blocking PPARγ activity using its inhibitor T0070907 or knocking down LXRα expression using short hairpin RNA reversed the effects of Septin 4 overexpression on foam cell formation and cholesterol handling. In conclusion, Septin 4 may serve an important role in preventing foam cell formation by activating PPARγ/LXRα signaling and subsequently enhancing ABCA1/G1 expression.

PMID:34035860 | PMC:PMC8135116 | DOI:10.3892/etm.2021.10195

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