Αρχειοθήκη ιστολογίου

Τετάρτη 22 Δεκεμβρίου 2021

Docosahexaenoic acid supplementation alleviates behavioral memory impairment caused via repeated administration of sevoflurane in aged rats

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Exp Ther Med. 2022 Jan;23(1):46. doi: 10.3892/etm.2021.10968. Epub 2021 Nov 15.

ABSTRACT

Elderly patients often need repeated surgical intervention, so it is important to determine the impact of repeated exposure to anesthetics on learning and memory. Docosahexaenoic acid (DHA) is considered to be an essential nutrient for maintaining brain health. The aim of the present study was to explore the potential effects of DHA on memory impairment induced by repeated sevoflurane anesthesia in aged rats. A total of 54 Sprague Dawley aged rats (18 months) were randomly divided into the following six groups: i) Control group; ii) sevoflurane group (Sev, 2.5% for 5 min); iii) DHA group (3 g/kg); iv) Sev + DHA (0.3 g/kg) group; v) Sev + DHA (1 g/kg) group; and vi) Sev + DHA (3 g/kg) group. Morris water maze experiment was performed to evaluate the learning and memory ability of the rats following treatment. H&E staining was used to observe any histological changes. Superoxide dismutase, malondialdehyde and glutathione peroxidase levels were detected using ELISA. Immunohistochemistry and western blotting were used to determine nuclear factor erythroid-2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) protein expression levels. Following repeated sevoflurane anesthesia, rats exhibited a prolonged escape latency. The number of times rats crossed the platform and the time spent in the target quadrant were also significantly reduced by repeated sevoflurane anesthesia. However, rats treated with Sev + DHA exhibited a reduced escape latency, whilst the number of times they crossed the platform and the time spent in the target quadrant increased compared with Sev treatment alone. Histopathological examination revealed that DHA treatment ameliorated the disordered neuron arrangement, deep staining of the neuronal nucleus pyknosis and cell edema observed in the brain tissue induced by repeated sevoflurane anesthesia. Furthermo re, the protein expression levels of Nrf2 and HO-1 were demonstrated to be significantly increased in rats treated with DHA and exposed to repeated sevoflurane anesthesia compared with those in untreated rats that underwent repeated sevoflurane anesthesia. In conclusion, the present study revealed that DHA exerted protective effects against impairments in learning and memory induced by repeated sevoflurane anesthesia in aged rats, which may be associated with the Nrf2/HO-1 signaling pathway.

PMID:34934425 | PMC:PMC8652387 | DOI:10.3892/etm.2021.10968

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Pathological complete response following cisplatin or carboplatin-based neoadjuvant chemotherapy for triple-negative breast cancer: A systematic review and meta-analysis

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Exp Ther Med. 2022 Jan;23(1):91. doi: 10.3892/etm.2021.11014. Epub 2021 Nov 26.

ABSTRACT

The addition of platinum compounds to standard neoadjuvant chemotherapy (NACT) for triple-negative breast cancer (TNBC) is highly controversial. Platinum agents, such as cisplatin and carboplatin, are DNA-damaging agents which exhibit activity in breast cancer, particularly in the TNBC subgroup. In order to assess the efficacy of each most representative platinum agent (cisplatin and carboplatin) in patients with TNBC treated with NACT, the present study performed a systematic review and meta-analysis of all available published studies on TNBC. A search of PubMed was performed to identify studies that investigated platinum-based NACT in patients with TNBC. The primary endpoints were the pooled rate of the pathological complete response (pCR) between cisplatin vs. carboplatin-based NACT. A total of 24 studies were selected (17 studies for carboplati n and 6 studies for cisplatin and 1 study with both carboplatin and cisplatin, with 20 prospective studies) for the analysis of 1,711 patients with TNBC. Overall, the pooled rate of pCR in patients treated with platinum-based NACT was 48%. No significant differences were observed between the rates of pCR obtained under carboplatin vs cisplatin treatment. The carboplatin pCR rate was 0.470 [95% confidence interval (CI), 0.401-0.539], while the cisplatin pCR rate was 0.473 (95% CI, 0.379-0.568). The comparison between these two categories revealed no significant differences (P=0.959). In the whole, the present study demonstrates that neoadjuvant platinum-based chemotherapy improves the pCR rate in patients with TNBC, regardless of the platinum agent used. Carboplatin may thus represent a viable option due to its more favorable toxicity profile.

PMID:34934456 | PMC:PMC8652390 | DOI:10.3892/etm.2021.11014

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Stomatin-knockdown effectively attenuates sepsis-induced oxidative stress and inflammation of alveolar epithelial cells by regulating CD36

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Exp Ther Med. 2022 Jan;23(1):69. doi: 10.3892/etm.2021.10992. Epub 2021 Nov 23.

ABSTRACT

Sepsis-induced acute lung injury is a type of lung disease with a high fatality rate that is characterized by acute inflammation. In the present study, the underlying role and potential mechanism of the stomatin (STOM) protein were investigated in lipopolysaccharide (LPS)-induced oxidative stress and inflammation in a mouse lung epithelial cell line, MLE-12. The expression levels of STOM and CD36 were measured using reverse transcription-quantitative PCR and western blotting. Subsequently, the expression levels of STOM and CD36 in LPS-treated MLE-12 cells were knocked down or overexpressed, respectively, via transfection with a small interfering RNA-STOM or a CD36-overexpression vector. An RNA immunoprecipitation (RIP) assay was used to determine the interaction between STOM and CD36, while Cell Counting Kit-8 assay and ELISA were performed to dete ct cell viability and oxidative stress, respectively. Moreover, western blotting and ELISA kits were used to detect the expression levels of associated inflammatory factors. The results of the present study demonstrated that STOM expression was upregulated in MLE-12 cells treated with LPS compared with the untreated control group. According to the Search Tool for the Retrieval of Interacting Genes/Proteins database, it was predicted that STOM and CD36 had the ability to interact with each other. The predicted binding between STOM and CD36 was verified using a RIP assay. The results demonstrated that STOM positively regulated the expression of CD36. Moreover, in LPS-treated MLE-12 cells, STOM-knockdown reversed the inhibitory effects of LPS on cell viability, and the promoting effects of LPS on oxidative stress and inflammation. These aforementioned changes were alleviated by the overexpression of CD36. To conclude, the results of the present study revealed that STOM may interact wit h CD36 to affect the levels of oxidative stress and inflammation in LPS-treated MLE-12 cells.

PMID:34934440 | PMC:PMC8649852 | DOI:10.3892/etm.2021.10992

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Lumbar Pneumorrhachis Associated With Basilar Skull Fractures

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Cureus. 2021 Nov 18;13(11):e19703. doi: 10.7759/cureus.19703. eCollection 2021 Nov.

ABSTRACT

Lumbar pneumorrhachis following head injury is rare and commonly asymptomatic but can be indicative of skull fracture and cerebrospinal fluid (CSF) leak, which may warrant intervention. A PubMed review of the literature was performed using a keyword search to identify cases examining lumbar pneumorrhachis following head injury. Our case series included two patients who had lumbar pneumorrhachis between September 2019 and May 2020 at our center. The literature review summarizes 16 patients from 14 prior reports of pneumorrhachis. In our two-patient case series, neither patient required direct intervention for either pneumorrhachis or CSF leak. Pneumorrhachis is rare following an isolated head injury and is associated with basilar skull fractures and CSF leak. Pneumorrhachis should alert clinicians to the possibility of a CSF leak, which may require int ervention.

PMID:34934572 | PMC:PMC8684351 | DOI:10.7759/cureus.19703

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In vitro and in vivo effects of AVA4746, a novel competitive antagonist of the ligand binding of VLA-4, in B-cell acute lymphoblastic leukemia

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Exp Ther Med. 2022 Jan;23(1):47. doi: 10.3892/etm.2021.10969. Epub 2021 Nov 15.

ABSTRACT

Treatment of resistant or recurrent acute lymphoblastic leukemia (ALL) remains a challenge. It was previously demonstrated that the adhesion molecule integrin α4, referred to hereafter as α4, mediates the cell adhesion-mediated drug resistance (CAM-DR) of B-cell ALL by binding to vascular cell adhesion molecule-1 (VCAM-1) on bone marrow stroma. In addition, it was previously observed that the blockade of α4 with natalizumab or inhibition using the small molecule antagonist TBC3486 sensitized relapsed ALL cells to chemotherapy. However, α4-targeted therapy is not clinically available for the treatment of leukemia to date. In the present study, the use of a novel non-peptidic small molecule integrin α4 antagonist, AVA4746, as a potential new approach to combat drug-resistant B-ALL was explored. An in vitro co-culture = model of primary B- ALL cells and an in vivo xenograft model of patient-derived B-ALL cells were utilized for evaluation of AVA4746. VLA-4 conformation activation, cell adhesion/de-adhesion, endothelial tube formation, in vivo leukemia cell mobilization and survival assays were performed. AVA4746 exhibited high affinity for binding to B-ALL cells, where it also efficiently blocked ligand-binding to VCAM-1. In addition, AVA4746 caused the functional de-adhesion of primary B-ALL cells from VCAM-1. Inhibition of α4 using AVA4746 also prevented angiogenesis in vitro and when applied in combination with chemotherapy consisting of Vincristine, Dexamethasone and L-asparaginase, it prolonged the survival of ~33% of the mice in an in vivo xenograft model of B-ALL. These data implicate the potential of targeting the α4-VCAM-1 interaction using AVA4746 for the treatment of drug-resistant B-lineage ALL.

PMID:34934426 | PMC:PMC8652384 | DOI:10.3892/etm.2021.10969

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Voluntary Cough Effectiveness and Airway Clearance in Neurodegenerative Disease

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J Speech Lang Hear Res. 2021 Dec 22:1-19. doi: 10.1044/2021_JSLHR-21-00308. Online ahead of print.

ABSTRACT

PURPOSE: Voluntary cough dysfunction is highly prevalent across multiple patient populations. Voluntary cough has been utilized as a screening tool for swallowing safety deficits and as a target for compensatory and exercise-based dysphagia management. However, it remains unclear whether voluntary cough dysfunction is associated with the ability to effectively clear the airwa y.

METHOD: Individuals with neurodegenerative disorders performed same-day voluntary cough testing and flexible endoscopic evaluations of swallowing (FEES). Participants who were cued to cough after exhibiting penetration to the vocal folds and/or aspiration with thin liquids during FEES met inclusion criteria. One-hundred and twenty-three trials were blinded, and the amount of residue before and after a cued cough on FEES was measured with a visual analog scale. Linear and binomial mixed-effects models examined the relationship between cough airflow during voluntary cough testing and the proportion of residue expelled.

RESULTS: Peak expiratory flow rate (p = .004) and cough expired volume from the entire epoch (p = .029) were significantly associated with the proportion of aspiration expelled from the subglottis. Peak expiratory flow rate values of 3.00 L/s, 3.50 L/s, and 5.30 L/s provided high predicted probabilities that ≥ 25%, ≥ 50%, and ≥ 80% asp irate was expelled. Accounting for depth of aspiration significantly improved model fit (p < .001).

CONCLUSIONS: These findings suggest that voluntary cough airflow is associated with cough effectiveness to clear aspiration from the subglottis, although aspiration amount and depth may play an important role in this relationship. These findings provide further support for the clinical utility of voluntary cough in the management of dysphagia.

PMID:34936376 | DOI:10.1044/2021_JSLHR-21-00308

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MiR-194-3p modulates the progression of colorectal cancer by targeting KLK10

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Histol Histopathol. 2021 Dec 22:18413. doi: 10.14670/HH-18-413. Online ahead of print.

ABSTRACT

BACKGROUND: A rich history of studies have manifested the importance of miRNAs to cancer progression, while miR-194-3p has been seldom explored.

OBJECTIVE: The purpose of this study is to unearth the way the KLK10/miR-194-3p axis modulates colorectal cancer (CRC).

METHODS: Differentially expressed genes of CRC in TCGA database were analyzed. Western blot and qRT-PCR were employed to test protein and mRNA expressions of two researched genes. Their targeting was confirmed using dual-luciferase. Biological behaviors of cells were tested by a series of cellular functional assays.

RESULT: Remarkably low miR-194-3p expression and high KLK10 expression were observed in cancer cells. Overexpressing miR-194-3p hindered the progression of CRC cells. Overexpression of miR-194-3p significantly weakened the promoting effect of upregulat ed KLK10 on cell migration, invasion and proliferation. Their targeting was verified by dual -luciferase assay. Therefore, miR-194-3p hindered cell behaviors of CRC through KLK10.

CONCLUSION: This investigation casts new light on the treatment of CRC through the KLK10/miR-194-3p axis.

PMID:34935123 | DOI:10.14670/HH-18-413

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