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Πέμπτη 26 Αυγούστου 2021

Fas regulates the apoptosis and migration of trophoblast cells by targeting NF-κB

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Exp Ther Med. 2021 Oct;22(4):1055. doi: 10.3892/etm.2021.10489. Epub 2021 Jul 23.

ABSTRACT

Placental trophoblast apoptosis is a major pathological feature of preeclampsia. Fas has been reported to be highly expressed in the placentas of patients with preeclampsia. However, the role and underlying mechanisms of Fas in the pathogenesis of preeclampsia have not been elucidated. In the present study, the expression of Fas in JAR human choriocarcinoma cells was overexpressed and knocked down to determine the function and possible mechanism of Fas in trophoblast cells in the progression of preeclampsia. The results of flow cytometry, Cell Counting Kit-8 and Transwell assays indicated that the overexpression of Fas promoted apoptosis, suppressed viability and impaired the migration of the human trophoblast cells. In addition, western blotting revealed that the overexpression of Fas increased the expression of nuclear factor kB (NF-kB), Bax, t umor necrosis factor α (TNF-α) and interleukin-2 (IL-2), and decreased the expression of Bcl-2 at the protein level in trophoblast cells. By contrast, the knockdown of Fas decreased the apoptosis of trophoblast cells and increased their viability and migration. In addition, the knockdown of Fas suppressed the expression of NF-κB, Bax, TNF-α and IL-2, and increased the expression of Bcl-2. Notably, the overexpression of NF-κB p65 attenuated the Fas knockdown-induced inhibition of apoptosis and acceleration of migration of the trophoblast cells. The overexpression of NF-κB in trophoblast cells also reversed the reduction in Bax expression and increase in Bcl-2 expression induced by Fas knockdown in trophoblast cells. These results indicate that Fas regulates the apoptosis and migration of trophoblast cells by targeting NF-κB, which suggests that the silencing of Fas is a promising therapeutic strategy for preeclampsia.

PMID:34434269 | PMC:PMC8353647 | DOI:10.3892/etm.2021.10489

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Solanum melongena allergy (A comprehensive review)

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Exp Ther Med. 2021 Oct;22(4):1061. doi: 10.3892/etm.2021.10495. Epub 2021 Jul 27.

ABSTRACT

The Solanaceae family, including, among other, eggplants, represents the sixth most widely cultivated crops around the globe. We review the current data regarding allergies to Solanum melongena (eggplants), generating symptoms that range from gastrointestinal to respiratory allergic reactions. Currently, there are more than 4 mechanisms and molecules presumably involved in triggering allergic reactions to Solanum melongena: The lipid transfer protein (LTP) pathway, the profilin pathway, polyphenol oxidase (PPO) mechanism and other molecules. Allergies may be triggered both by pollen respiratory reactions and fruit intake. There is also an important cross-reactivity mechanism revealed by recent studies. Our literature review revealed many case series studies, some with in-depth molecular analysis of the triggering mechanism. However, wide population studies are still scarce. Current geographical distribution of the crops and population migrations should enhance the awareness of allergy and immunology specialists, ENT specialists, emergency physicians and pediatricians to the need for proper routine laboratory testing for possible Solanum allergy.

PMID:34434275 | PMC:PMC8353643 | DOI:10.38 92/etm.2021.10495

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Dexmedetomidine alleviates inflammation in neuropathic pain by suppressing NLRP3 via Nrf2 activation

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Exp Ther Med. 2021 Oct;22(4):1046. doi: 10.3892/etm.2021.10479. Epub 2021 Jul 22.

ABSTRACT

The aim of the present study was to investigate the mechanism by which dexmedetomidine (DEX) alleviates neuropathic pain in a chronic constriction injury (CCI) model in rats. A CCI rat model was established through sciatic nerve ligation. CCI rats were treated with DEX, the nuclear factor erythroid 2-related factor 2 (Nrf2) inhibitor ML385, the NLR family pyrin domain containing 3 (NLRP3) antagonist MCC950 and/or the NLRP3 activator nigericin. The mechanical withdrawal threshold (MWT) was measured to assess the pain sensitivity of CCI rats. Hematoxylin and eosin staining and TUNEL staining were used to examine spinal injury and apoptosis, respectively. ELISA was used to quantify the levels of inflammatory factors. The expression levels of Nrf2 and NLRP3 were also examined. The results indicated that a decrease in MWT and increases in spinal cord injury, apoptosis and inflammatory factors were detected in CCI rats compared with control rats. Spinal inflammation was abrogated in DEX-treated CCI rats. Compared with the model group, an increase in MWT and decreases in spinal cord injury, apoptosis and inflammatory factors were detected in rats treated with MCC950, while the opposite effects were observed in rats treated with nigericin. The opposite effects on these indicators were observed in the DEX + ML385 and MCC950 + ML385 groups compared with the DEX and MCC950 groups, respectively. MWT was increased, while spinal cord injury, apoptosis and inflammation decreased in the nigericin + DEX group compared with the nigericin group. In summary, the results of the present study indicated that DEX reduced neuropathic pain in CCI rats by suppressing NLRP3 through Nrf2 activation.

PMID:34434260 | PMC:PMC8353619 | DOI:10.3892/etm.2021.10479

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Role and dynamics of matrix metalloproteinase 9 and tissue inhibitor of metalloproteinase 1 in burn patients

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Exp Ther Med. 2021 Oct;22(4):1062. doi: 10.3892/etm.2021.10496. Epub 2021 Jul 27.

ABSTRACT

Burn injuries can trigger tissue changes that can explain the variation in the level of different biochemical markers that can be recorded both locally or systemically. Some events observed in burn wounds such as vascular hyperpermeability have been associated with the release of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) after trauma. Because it is unknown whether the serum levels of MMP-9 and TIMP-1 are a consequence of these destructions or a local response to thermal damage, we decided to follow their dynamics. Twenty-five patients (mean age 49.40±17.55 years) with a total body surface area (TBSA) affected by a thermal burn of <25% and 30 healthy subjects (mean age 49.70±8.04 years) were enrolled in the present study. Enzyme immunoassays were used to measure the serum levels of MMP-9 and TIMP-1. Our results show ed that MMP-9 was increased 6.25-fold immediately after injury compared to the controls and remained on a plateau throughout the 7-day monitoring period. TIMP-1 showed an upward trend with an increase of 49.52% on the seventh day after triggering insult. The time-course of the MMP-9/TIMP-1 ratio followed the inverse dynamics of TIMP-1 starting from a ratio value measured at admission 3.82-fold higher than the one observed in the healthy volunteers and a highly statistically significant correlation between the values measured at different time-points during the monitoring period (P<0.001). The results of this retrospective study indicate that the MMP-9/TIMP-1 ratio may provide information on local changes over time, starting from the triggering insult, and may be considered as a predictive biomarker of burn evolutivity.

PMID:34434276 | PMC:PMC8353633 | DOI:10.3892/etm.2021.10496

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Network pharmacology-based prediction of the active compounds and mechanism of Buyang Huanwu Decoction for ischemic stroke

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Exp Ther Med. 2021 Oct;22(4):1050. doi: 10.3892/etm.2021.10484. Epub 2021 Jul 23.

ABSTRACT

Buyang Huanwu Decoction (BYHWD) is used to promote blood circulation and is widely used in Chinese clinical practice for the treatment and prevention of ischemic cerebral vascular diseases. However, the mechanism and active compounds of BYHWD used to treat ischemic stroke are not well understood. The current study aimed to identify the potential active components of BYHWD and explore its mechanism using network pharmacology and bioinformatics analyses. The compounds of BYHWD were obtained from public databases. Oral bioavailability and drug-likeness were screened using the absorption, distribution, metabolism and excretion (ADME) criteria. Components of BYHWD, alongside the candidate targets of each component and the known therapeutic targets of ischemic stroke were collected. A network of target gene compounds and cerebral ischemia compounds was established using network pharmacology data sources. The enrichment of key targets and pathways was analyzed using STRING and DAVID databases. Moreover, three of key targets [IL6, VEGFA and hypoxia-inducible-factor-1α (HIF-1α)] were verified using western blot analysis. Network analysis determined 102 compounds in seven herbal medicines that were subjected to ADME screening. A total of 42 compounds as well as 79 genes formed the principal pathways associated with ischemic stroke. The 16 key compounds identified were baicalein, beta-carotene, baicalin, kaempferol, luteolin, quercetin, hydroxysafflor yellow A, isorhamnetin, bifendate, formononetin, calycosin, astragaloside IV, stigmasterol, sitosterol, Z-ligustilide, and dihydrocapsaicin. The core genes in this network were IL6, TNF, VEGFA, HIF-1α, MAPK1, MAPK3, JUN, STAT3, IL1B and IL10. Furthermore, the TNF, IL17, apoptosis, PI3K-Akt, toll-like receptor, MAPK, NF-κB and HIF-1 signaling pathways were identified to be associated with ischemic stroke. Compared with the control group (no treatment), BYHWD significantly inhibited the expression of IL6 and increase the expression of HIF-1α and VEGFA. Network pharmacology analyses can help to reveal close interactions between multi-components and multi-targets and enhance understanding of the potential effects of BYHWD on ischemic stroke.

PMID:34434264 | PMC:PMC8353622 | DOI:10.3892/etm.2021.10484

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A multidisciplinary approach in the diagnostic challenge of GIST

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Exp Ther Med. 2021 Oct;22(4):1063. doi: 10.3892/etm.2021.10497. Epub 2021 Jul 27.

ABSTRACT

Gastrointestinal stromal tumors (GISTs) are the most common malignant mesenchymal lesions of the gastrointestinal tract. They originate from the interstitial cells of Cajal and are characterized by overexpression of the tyrosine kinase receptor, protein product of c-KIT gene (KIT). In this retrospective study, conducted over a period of 10 years, we retrieved from our database, a total number of 57 patients, admitted and operated in the surgical department of 'Sf. Pantelimon' Emergency Clinical Hospital, Bucharest, for digestive tumors, histopathologically confirmed as GISTs. More than half of the cases presented as surgical emergencies and the tumors found during the surgical procedures, which proved to be GISTs, were sometimes difficult to differentiate from other mesenchymal tumors, both for the clinician and the pathologist. The diagnosis of GIST relies mostly on pathology and immunohistochemistry, but also on clinical and imagistic data. The most common emergencies were digestive hemorrhage (associated with gastric location), followed by intestinal obstruction (especially for the ileal localization). The largest dimensions corresponded to gastric location. For selected indications (upper digestive sites), upper digestive endoscopy approaches 100% sensitivity. This study focuses on diagnosis of GISTs sustained by both clinical and imagistic methods, along with histopathology and immunohistochemistry techniques, according to the World Health Organization 2019 criteria. Even though the differential diagnosis of these tumors is challenging, an interdisciplinary cooperation with a multiple approach increases the odds of a correct positive diagnosis.

PMID:34434277 | PMC:PMC8353641 | DOI:10.3892/etm.2021.10497

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Inhibition of autophagy promotes human RSV NS1-induced inflammation and apoptosis in vitro

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Exp Ther Med. 2021 Oct;22(4):1054. doi: 10.3892/etm.2021.10488. Epub 2021 Jul 23.

ABSTRACT

Human respiratory syncytial virus (RSV) is a major health challenge due to the lack of a safe and effective vaccine and antiviral drugs. RSV non-structural protein 1 (NS1) is the main inhibitor of antiviral signaling pathways in RSV infection; however, the underlying mechanism is unclear. The aim of the present study was to investigate of the role of NS1 and its relationship with autophagy. NS1-Flag plasmid was transfected into A549 cells and the levels of inflammatory cytokines, autophagy markers and apoptosis were detected. In addition, the cells were treated with an autophagy inhibitor, 3-methyladenine for 12 h prior to transfection with the NS1 plasmid to explore the role of autophagy in NS1-transfected cells. The results showed that the production of inflammatory cytokines and autophagy was induced in NS1-transfected cells, and indicated tha t autophagy prevents the production of cytokines and the activation of apoptosis. Furthermore, the results demonstrated that NS1 activated autophagy partly through the mTOR-p70 S6 kinase signaling pathway. The results suggest that autophagy induced by NS1 transfection through the mTOR pathway can hinder the production of inflammatory cytokines and interferon-α and inhibit cell apoptosis, which may help to explain why autophagy has been shown to be beneficial to viral replication in most studies.

PMID:34434268 | PMC:PMC8353648 | DOI:10.3892/etm.2021.10488

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Omega plate for the treatment of acetabular fractures involving the quadrilateral plate

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Exp Ther Med. 2021 Oct;22(4):1064. doi: 10.3892/etm.2021.10498. Epub 2021 Jul 27.

ABSTRACT

This retrospective study aimed to assess the outcome of a modified Stoppa approach using an anatomically precontoured plate for the treatment of acetabular fractures. In total, 30 patients (mean age 50.3 years; 25 men and 5 women) with acetabular fractures were treated between January 1, 2018 and December 31, 2019. In all 30 cases, fracture reduction was performed through a modified Stoppa approach and fixed with the omega plate. In specific fracture patterns, additional approaches were needed (lateral window in 4 cases and posterior Kocher-Langenbeck approach in 7 cases). Patients were assessed for restoration of the hip joint congruency, complications, and overall fracture reduction. Quality of reduction was categorized based on Matta's radiological principles and to assess functional outcome the Merle d'Aubigné-Postel and Harris hip score was used. The average anesthesia time was 253.6 min, the mean intraoperative blood lost was 266.6 ml and the mean intraoperative fluoroscopy dose was 3.21 mGy. According to Matta criteria for reduction quality, anatomical reduction was recorded in 22 cases, imperfect reduction in 6 cases and 2 cases had poor reduction. The average follow-up was 22.5 months. Malunion, loss of reduction or implant loosening were not recorded. Late complications included one case of avascular necrosis of the femoral head and post-traumatic arthritis changes in 5 cases. At the final follow-up, a mean Merle d'Aubigné-Postel score of 13.26±4.46 and a mean Harris score of 86.03±13.37 were recorded. The possibility of an anatomically precontoured plate with subsequent lower operative time combined with stable fixation of the primary acetabular fracture fragments and the quadrilateral plate makes the omega plate a viable option for treating acetabular fractures with a very low complication rate and good to e xcellent results in 89% of the cases.

PMID:34434278 | PMC:PMC8353621 | DOI:10.3892/etm.2021.10498

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CGFe and TGF-β1 enhance viability and osteogenic differentiation of human dental pulp stem cells through the MAPK pathway

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Exp Ther Med. 2021 Oct;22(4):1048. doi: 10.3892/etm.2021.10482. Epub 2021 Jul 23.

ABSTRACT

The present study aimed to evaluate the effects of concentrated growth factor exudate (CGFe) and TGF-β1 on the viability and osteogenic differentiation of human dental pulp stem cells (hDPSCs). CGFe was prepared from the peripheral blood of healthy donors (obtained with informed consent). STRO-1+ hDPSCs were isolated from dental pulp tissues and treated in four groups: i) Control; ii) TGF-β1 (1 ng/ml); iii) 100% CGFe; and iv) TGF-β1 (1 ng/ml) + 100% CGFe group. hDPSC viability was measured via MTT assay. The osteogenic differentiation of hDPSCs was quantified via alkaline phosphatase (ALP) activity, western blotting and reverse transcription-quantitative PCR assays. CGFe and TGF-β1 enhanced hDPSC viability, upregulated ALP activity, upregulated the expression of phosphorylated (p)-ERK1/2, p-JNK and p-p38 in hDPSCs, and promoted tra nscription and protein expression of osteogenic-related genes (bone sialoprotein, Runt-related transcription factor 2 and osteocalcin) in hDPSCs. The present study demonstrated that CGFe and TGF-β1 facilitated the viability and osteogenic differentiation of hDPSCs potentially through activation of the MAPK signaling pathway.

PMID:34434262 | PMC:PMC8353646 | DOI:10.3 892/etm.2021.10482

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External cervical resorption: Radiological diagnosis and literature (Review)

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Exp Ther Med. 2021 Oct;22(4):1065. doi: 10.3892/etm.2021.10499. Epub 2021 Jul 27.

ABSTRACT

External cervical resorption (ECR) is a relatively unknown and insidious pathology characterized by the loss of hard dental tissues such as: Enamel, cementum and dentine due to clastic function. It begins as a localized resorptive process that initiates on the area of the root beneath the epithelial attachment and the coronal part of the alveolar process, involving vital and non-vital tissues. Despite the fact that there are several potential predisposing factors related to ECR, its aetiology still remains poorly understood and more research is needed to establish the cause-and-effect relationship of all the etiological factors. Improved radiographic detection using cone-beam computed tomography (CBCT) is required in order to correctly classify and assess this entity. This provides a three-dimensional insight into the lesion, regarding the locati on, the size, the depth and the circumferential spread of the ECR defect. It also allows establishment of the most efficacious treatment plan and management. The purpose of this literature review is to cover the relevant literature concerning the etiology, pathogenesis, clinical and radiological presentation and management of ECRs (based on the CBCT findings).

PMID:34434279 | PMC:PMC8353645 | DOI:10.3892/etm.2021.10499

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