MicroRNA-139-5p improves sepsis-induced lung injury by targeting Rho-kinase1

xlomafota13 shared this article with you from Inoreader MicroRNA-139-5p improves sepsis-induced lung injury by targeting Rho-kinase1 Via Experimental and therapeutic medicine Exp Ther Med. 2021 Oct;22(4):1059. doi: 10.3892/etm.2021.10493. Epub 2021 Jul 26. ABSTRACT Sepsis-induced acute lung injury (ALI) is an inflammatory process that involves inflammatory cytokine production and cell apoptosis. In the present study, the regulatory role of microRNA (miR)-139-5p in sepsis-induced ALI was investigated using a murine model of cecal ligation puncture (CLP) and an in vitro model using lipopolysaccharide (LPS)-induced normal human bronchial epithelial cells (NHBEs). Sepsis-induced pathological changes in the lungs of ALI mice were detected using hematoxylin and eosin staining. Lung water content was determined, and the expression of proinflammatory cytokines in the bronchoalveolar lavage fluid and serum of sepsis-induced ALI mice were quantified using ELISA. The levels of oxidative stress in lung tissues were determined using commercial kits. The degree of apoptosis was determined using a TUNEL assay. The expression levels of miR-139-5p and Rho-kinase 1 (ROCK1) were determined using reverse transcription-quantitative PCR and western blot analyses. A dual-luciferase reporter assay was used to confirm the direct targeting of ROCK1 by miR-139-5p. NHBEs were co-transfected with vectors expressing ROCK1 (or empty vector) and miR-139-5p mimics or control mimics prior to LPS treatment. The transcriptional activity of caspase-3, the ratio of apoptotic cells, the expression levels of mucin 5AC, mucin 1, TNF-α, IL-1β, IL-6, NLR family pyrin domain containing 3, apoptosis-associated speck-like protein containing a CARD and caspase-1 were evaluated. Compared with the normal group, mice that underwent CLP exhibited abnormal lung morphology, enhanced production of TNF-α, IL-1β and IL-6, increased reactive oxygen species (ROS), malondialdehyde and lactate dehydrogenase levels, an increased proportion of apoptotic cells and increased ROCK1 expression. Superoxide dismutase, glutathione peroxidase and miR-139-5p levels were decreased following CLP. In the NHBEs, stimulation with LPS caused a marked increase in inflammatory cytokine levels and apoptosis compared with the untreated cells. Overexpression of miR-139-5p attenuated cell apoptosis and inflammation. Overexpression of ROCK1 in NHBEs restored the ROS levels and proinflammatory cytokine production inhibited by miR-139-5p. In conclusion, miR-139-5p alleviated sepsis-induced ALI via suppression of its downstream target, ROCK1, suggesting that miR-139-5p may hold promise in the treatment of sepsis-induced ALI. PMID:34434273 | PMC:PMC8353635 | DOI:10.3892/etm.2021.10493 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

NEIL3 contributes toward the carcinogenesis of liver cancer and regulates PI3K/Akt/mTOR signaling

xlomafota13 shared this article with you from Inoreader <em>NEIL3</em> contributes toward the carcinogenesis of liver cancer and regulates PI3K/Akt/mTOR signaling Via Experimental and therapeutic medicine Exp Ther Med. 2021 Oct;22(4):1053. doi: 10.3892/etm.2021.10487. Epub 2021 Jul 23. ABSTRACT Liver cancer is one of the top three fatal types of cancer and it causes several thousands of mortalities each year. The main treatment is surgical resection which shows little benefit for patients with recurrence or metastasis. NEIL3 promotes progression and predicts survival in cancer. However, its role in liver cancer remains unclear. Based on data in the TCGA database, NEIL3 exhibited much higher expression in liver cancer tissues and was clinically correlated with tumor grade in patients with liver cancer. Furthermore, high NEIL3 expression caused shorter survival times. In liver cancer cell lines, NEIL3 showed abundant expression. When NEIL3 was knocked down in HepG2 and Huh-7 cells, cell abilities including proliferation, growth, migration and invasion, exhibited deficiency to different extents. Cell cycl e transition was blocked at the G2 phase and the cell apoptotic rate increased notably. In addition, the phosphorylation levels of Akt, PI3K and mTOR were increased following NEIL3-overexpression but decreased following NEIL3-knockdown. In conclusion, NEIL3 contributes toward development and/or progression in liver cancer and regulates PI3K/Akt/mTOR signaling. PMID:34434267 | PMC:PMC8353638 | DOI:10.3892/etm.2021.10487 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Primary pelvic exenteration: Our experience with 23 patients from a single institution

xlomafota13 shared this article with you from Inoreader Primary pelvic exenteration: Our experience with 23 patients from a single institution Via Experimental and therapeutic medicine Exp Ther Med. 2021 Oct;22(4):1060. doi: 10.3892/etm.2021.10494. Epub 2021 Jul 26. ABSTRACT This study was designed with an aim to share our experience of primary pelvic exenterations. The study included 23 patients with different types of pelvic cancer enrolled at a single institution between November 2011 and July 2020. The patient mean age was 55 years (range, 43-72 years) and the oncological indications included: Stage IVa cervical cancer (11 cases, 48.9%), stage IVa endometrial cancer (1 case, 4.3%), stage IVa vaginal cancer (6 cases, 26%), stage IIIb bladder cancer (3 cases, 13%), stage IIIc rectal cancer (1 case, 4.3%) and undifferentiated pelvic sarcoma (1 case, 4.3%). Total, anterior, and posterior pelvic exenterations were performed on 34.4, 56.5 and 13% of cases, respectively. Related to levator ani muscle, 13 (56.5%) pelvic exenterations were supralevatorian, 10 (43.5%) infralevatorian, and 5 (21.7%) were infralevatorian wit h vulvectomy. No major intraoperative complications occurred. Seven patients (30.5%) developed early complications, 4 of them (17.4%) required reoperation and 1 (4.3%) perioperative death caused by a pulmonary embolism was recorded. Only 1 patient experienced a late complication, a urostomy stenosis. Over a median follow-up period of 35 months, 8 (34.8%) patients died. The median overall survival (OS) was 33 months (range, 1-96 months). The 2-year and 5-year survival rates were 72 and 66%, respectively. Primary pelvic exenteration may be related with various postoperative complications, without high perioperative morality and with long-term survival. PMID:34434274 | PMC:PMC8353644 | DOI:10.3892/etm.2021.10494 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

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

xlomafota13 shared this article with you from Inoreader Fas regulates the apoptosis and migration of trophoblast cells by targeting NF-κB Via Experimental and therapeutic medicine 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 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Solanum melongena allergy (A comprehensive review)

xlomafota13 shared this article with you from Inoreader <em>Solanum melongena</em> allergy (A comprehensive review) Via Experimental and therapeutic medicine 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 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

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

xlomafota13 shared this article with you from Inoreader Dexmedetomidine alleviates inflammation in neuropathic pain by suppressing NLRP3 via Nrf2 activation Via Experimental and therapeutic medicine 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 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

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

xlomafota13 shared this article with you from Inoreader Role and dynamics of matrix metalloproteinase 9 and tissue inhibitor of metalloproteinase 1 in burn patients Via Experimental and therapeutic medicine 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 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

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

xlomafota13 shared this article with you from Inoreader Network pharmacology-based prediction of the active compounds and mechanism of Buyang Huanwu Decoction for ischemic stroke Via Experimental and therapeutic medicine 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 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

A multidisciplinary approach in the diagnostic challenge of GIST

xlomafota13 shared this article with you from Inoreader A multidisciplinary approach in the diagnostic challenge of GIST Via Experimental and therapeutic medicine 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 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

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

xlomafota13 shared this article with you from Inoreader Inhibition of autophagy promotes human RSV NS1-induced inflammation and apoptosis <em>in vitro</em> Via Experimental and therapeutic medicine 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 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.