Rankinblake7152
Objective Heat stroke (HS) elicits the systemic inflammatory responses that result in multiple organ dysfunction (MOD). Heat shock response and autophagy are activated during heat stress for removal of damaged organelles and proteins, emerging as a major regulator of cellular homeostasis. Ethyl pyruvate (EP) is a derivative of pyruvic acid and possesses antioxidant and anti-inflammatory effects. This study aims to investigate the effects of EP on MOD in HS rats and explore the possible mechanisms.Method Anesthetized rats were placed in a heating chamber (42 °C) to elevate the core body temperature attaining to 42.9 °C. Rats were then moved to room temperature and monitored for 6 h. EP (60 mg/kg, i.v.) was administered 30 min prior to heat exposure.Results Results showed that EP significantly reduced HS-induced increases in plasma levels of LDH, CPK, GPT and CK-MB, reversed the decrease of platelet counts, and alleviated intestinal mucosal and pulmonary damage. Moreover, EP reduced pro-inflammatory protein, including TNF-α, IL-6, IL-1β, HMGB1 and iNOS, and induced stress proteins, heme oxygenase-1 (HO-1), heat shock protein (HSP) 70 and HSP90 in the liver of HS rats. The levels of HS-activated autophagy-regulatory proteins were affected by EP, in which the phosphorylated mTOR and AKT were reduced, and the phosphorylated AMPK increased, accompanied with upregulation in ULK1, Atg7, Atg12 and LC3II, and downregulation of p62.Conclusion In conclusion, EP ameliorated HS-induced inflammatory responses and MOD, and the underlying mechanism is associated with the induction of the stress proteins HO-1 and HSP70 as well as restorage of autophagy.
Huoxiangzhengqi oral liquid (HXZQ-OL), a traditional Chinese medicine formula, has antibacterial, anti-inflammation and gastrointestinal motility regulation effects.
The study investigates the anti-allergic activity and underlying mechanism of HXZQ-OL.
IgE/Ag-mediated RBL-2H3 cells were used to evaluate the anti-allergic activity of HXZQ-OL (43.97, 439.7 and 4397 μg/mL)
. The release of cytokines and eicosanoids were quantified using ELISA. RT-qPCR was used to measure the gene expression of cytokines. The level of intracellular Ca
was measured with Fluo 3/AM. Immunoblotting analysis was performed to investigate the mechanism of HXZQ-OL. In the passive cutaneous anaphylaxis (PCA), BALB/c mice (5 mice/group) were orally administrated with HXZQ-OL (263.8, 527.6 and 1055 mg/kg/d) or dexamethasone (5 mg/kg/d, positive control) for seven consecutive days.
HXZQ-OL not only inhibited degranulation of mast cells (IC
, 123 μg/mL), but also inhibited the generation and secretion of IL-4 (IC
, 171.4 μg/mL), TNF-α (IC
, 88.4 μg/mL), LTC4 (IC
, 52.9 μg/mL) and PGD2 (IC
, 195.8 μg/mL). Moreover, HXZQ-OL suppressed the expression of IL-4 and TNF-α mRNA, as well as the phosphorylation of Fyn, Lyn and multiple downstream signalling proteins including MAPK and PI3K/NF-κB pathways. In addition, HXZQ-OL (527.5 mg/kg) attenuated the IgE-mediated PCA with 55% suppression of Evans blue exudation in mice.
HXZQ-OL attenuated the activation of mast cell and PCA. Therefore, HXZQ-OL might be used as an alternative treatment for allergic diseases.
HXZQ-OL attenuated the activation of mast cell and PCA. Therefore, HXZQ-OL might be used as an alternative treatment for allergic diseases.Introduction In the context of limited research assessing outcomes following mild traumatic brain injury (mTBI) in older adults, this study evaluated cognitive outcomes through prospective memory, and expected that performance of an older mTBI group (≥65 years) would be lower compared to orthopedic and community controls. The study also explored whether cognitive resources (retrospective memory, executive function) moderated any association between presenting Glasgow Coma Scale (GCS) and prospective memory.Method At three-months post-injury, a mTBI group (n = 39), an orthopedic control group (n = 63), and a community control group (n = 46) completed a neuropsychological assessment, including (i) prospective memory, using a standardized paper-and-pencil task (Cambridge Prospective Memory Test), an augmented reality task and a naturalistic task, and (ii) standardized measures of retrospective memory (Hopkins Verbal Learning Test) and executive function (Trail Making Test). Group performances were compared, and esolve or persist over time.Background The monoamine neurotransmitter disorders are neurometabolic syndromes caused by disturbances in the synthesis, transport and metabolism of the biogenic amines (the catecholamines dopamine, norepinephrine and epinephrine; serotonin), which are increasingly recognized as an expanding group of inherited neurometabolic syndromes.Case Description A 6-month-old male infant who presented with developmental delay and suspected cerebral palsy was diagnosed with infantile parkinsonism-dystonia-2 (MIM 618049). The whole-exome sequencing identified a homozygous c.710C > T (p.Pro237His) transition in the monoamine transporter gene SLC18A2, which was due to paternal uniparental disomy (UPD) of chromosome 10p15.3q26.3, resulting in brain dopamine-serotonin vesicular transport disease. Sanger sequencing confirmed that his unaffected father carried the same mutation in the heterozygous state, while his mother did not carry the same mutation. Autosomal recessive gene mutations in SLC18A2 has been identified in three families in different countries. C188-9 research buy The infant was treated with pramipexole, a dopamine agonist, and the static tremor was better compared with that before treatment, but the movement disorder was not significantly improved.Conclusion This case confirmed the causal mutation of SLC18A2 gene and brain dopamine-serotonin vesicular transport disease, which suggested the mechanism of UPD homozygous formation, and confirmed that dopamine agonist treatment could improve some symptoms in affected individuals.
Liver resection (LR) and radiofrequency ablation (RFA) are commonly used for the treatment of recurrent hepatocellular carcinoma (HCC), but the optimal treatment modality remains unclear. We aimed to compare the efficacy and safety of LR vs RFA for recurrent HCC.
We searched PubMed, Embase, Web of Science, and the Cochrane Library for relevant studies. The primary outcomes were overall survival (OS) and disease-free survival (DFS). The secondary outcomes were major complications and hospital stay.
Eighteen studies with 1991 patients with recurrent HCC were included. The pooled hazard ratio (HR) for OS demonstrated that LR had significantly better OS than RFA in recurrent HCC (HR, 0.81; 95% confidence interval [CI], 0.68-0.95). Specifically, LR was associated with higher 2-, 3- and 4-year OS rates compared with RFA. The pooled HR for DFS showed no significant difference between LR and RFA during the whole follow-up period (HR, 0.90; 95% CI, 0.76-1.07). However, LR was associated with significantly higher 2- to 5-year DFS rates compared to RFA.
