Aqueous extract of Amydrium sinense (Engl.) H. Li alleviates hepatic fibrosis by suppressing hepatic stellate cell activation through inhibiting Stat3 signaling

Background: The present study aimed to investigate the protective effect of the water extract of Amydrium sinense (Engl.) H. Li (ASWE) against hepatic fibrosis (HF) and clarify the underlying mechanism.Methods: The chemical components of ASWE were analysed by a Q-Orbitrap high-resolution mass spectrometer. In our study, an in vivo hepatic fibrosis mouse model was established via an intraperitoneal injection of olive oil containing 20% CCl4. In vitro experiments were conducted using a hepatic stellate cell line (HSC-T6) and RAW 264.7 cell line. A CCK-8 assay was performed to assess the cell viability of HSC-T6 and RAW264.7 cells treated with ASWE. Immunofluorescence staining was used to examine the intracellular localization of signal transducer and activator of transcription 3 (Stat3). Stat3 was overexpressed to analyse the role of Stat3 in the effect of ASWE on HF.Results: Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses showed that candidate targets of ASWE, associated with protective effects against hepatic fibrosis, were related to inflammation response. ASWE ameliorated CCl4-induced liver pathological damage and reduced the liver index and alanine transaminase (ALT) and aspartate transaminase (AST) levels. ASWE also decreased the serum levels of collagen Ⅰ (Col Ⅰ) and hydroxyproline (Hyp) in CCl4-treated mice. In addition, the expression of fibrosis markers, including α-SMA protein and Acta2, Col1a1, and Col3a1 mRNA, was downregulated by ASWE treatment in vivo. The expression of these fibrosis markers was also decreased by treatment with ASWE in HSC-T6 cells. Moreover, ASWE decreased the expression of inflammatory markers, including the Tnf-α, Il6 and Il1β, in RAW264.7 cells. ASWE decreased the phosphorylation of Stat3 and total Stat3 expression and reduced the mRNA expression of the Stat3 gene in vivo and in vitro. ASWE also inhibited the nuclear shuttling of Stat3. Overexpression of Stat3 weakened the therapeutic effect of ASWE and accelerated the progression of HF.Conclusion: The results show that ASWE protects against CCl4-induced liver injury by suppressing fibrosis, inflammation, HSC activation and the Stat3 signaling pathway, which might lead to a new approach for preventing HF

Yao medicine Amydrium hainanense suppresses hepatic fibrosis by repressing hepatic stellate cell activation via STAT3 signaling

Ethnopharmacological relevance: Hepatic fibrosis (HF) occurs in response to chronic liver injury and may easily develop into irreversible liver cirrhosis or even liver cancer. Amydrium hainanense water extract (AHWE) is a water-soluble component extracted from the Yao medicine Amydrium hainanense (H.Li, Y.Shiao & S.L.Tseng) H.Li, which is commonly used for treating inflammatory diseases in folk. Previous evidence suggested that AHWE significantly inhibited hepatic stellate cell activation. However, little is known regarding the therapeutic effect of AHWE in HF and its underlying action mechanism.Objective: Investigation of the therapeutic effect of AHWE in HF and its underlying mechanism.Methods: The therapeutic effect of AHWE was tested in vivo using an HF mouse model via an intraperitoneal injection of carbon tetrachloride (CCl4). Histological evaluation of liver injury and fibrosis were tested by H&E staining and Masson’s trichrome staining. Serum levels of ALT, AST, collagen type I (Col I), and hydroxyproline (HYP) were measured. The mRNA expression of liver fibrotic and inflammatory genes were tested, and the protein levels of alpha smooth muscle actin (α-SMA) and signal transducers and activators of transcription 3 (STAT3) were analyzed. The in vitro experiments were conducted using HSC-T6 and RAW264.7 cell lines.Results: Treatment with AHWE significantly reversed histopathological liver damage and liver function abnormalities in CCl4 mouse model. Also, the serum levels of ALT, AST, Col I, and HYP in CCl4-induced HF mice were improved in AHWE treatment. Further, AHWE showed a remarkable inhibitory effect on the expression of fibrosis markers (Acta2, Col1a1, and Col3a1) and inflammatory factors (Stat3, Tnfa, Il6, and Il1b) induced by CCl4. The results of in vitro experiments were consistent with those obtained in vivo. In addition, it is shown that STAT3 signaling was involved in the anti-fibrotic effects of AHWE as evidenced by STAT3 overexpression.Conclusion: The present study proposed a novel ethnomedicine for HF and suggested the underlying role of STAT3 signaling pathway regulation in this anti-fibrotic effect of the proposed medicine. These findings would serve as solid scientific evidence in support of the development of AHWE as a novel alternative or complementary therapy for HF prevention and treatment

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Correction to: Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

The original version of this article unfortunately contained a mistake

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Local and Systemic Oxidative Stress and Glucocorticoid Receptor Levels in Chronic Obstructive Pulmonary Disease Patients

BACKGROUND: Previous studies have indicated that oxidative stress plays an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD)

Combined HIF-1α and SHH Up-Regulation Is a Potential Biomarker to Predict Poor Prognosis in Postoperative Hepatocellular Carcinoma

Background Hypoxia-inducible factor-1α (HIF-1α) or sonic hedgehog (SHH) is associated with hepatocellular carcinoma (HCC) progression. Hypoxia inhibits ferroptosis, which induces cancer cell death. However, the correlation between the combined HIF-1α and SHH up-regulation with prognosis, and the association between SHH and ferroptosis remain unclear. This study aimed to investigate them. Methods We detected the expression of HIF-1α and SHH in HCC. Cox regression, clinical data, and Kaplan–Meier analyses were performed. In vitro cell experiments verified the relationship between HIF-1α and SHH, and observed the invasion of hypoxic HCC cells. The correlation between SHH and ferroptosis was also analyzed. Results HIF-1α and SHH expression levels were significantly correlated with HCC (p < 0.0001). HIF-1α and SHH expression levels were found to be associated with TNM stage (p = 0.0121, p = 0.0078, respectively), vascular invasion (p < 0.0001, p < 0.0001, respectively), and recurrence (p = 0.0212, p = 0.0392, respectively). The combined upregulation of HIF-1α and SHH was an independent factor for predicting the overall survival (OS) of patients with HCC (p = 0.003), who had the shortest OS (p = 0.0009). SHH paralleled the increase in HIF-1α expression, which promotes cancer cell invasion. The upregulation of SHH was related to the inhibition of the expression of ferroptosis-related factors (FANCD2, p < 0.0001 and FTH1, p = 0.0009) in HCC. Conclusion Combined HIF-1α and SHH upregulation is a potentially poor prognosis indicator in patients with HCC because the upregulation of SHH inhibits ferroptosis in hypoxic cancer cells

Genetic structure and evolutionary history of three alpine sclerophyllous oaks in East Himalaya-Hengduan Mountains and adjacent regions

The East Himalaya-Hengduan Mountains (EH-HM) region has a high biodiversity and harbours numerous endemic alpine plants. This is probably the result of combined orographic and climate oscillations occurring since late Tertiary. Here, we determined the genetic structure and evolutionary history of alpine oak species (including Q. spinosa, Q. aquifolioides and Q. rehderiana) using both cytoplasmic-nuclear markers and ecological niche models (ENMs), and elucidated the impacts of climate oscillations and environmental heterogeneity on their population demography. Our results indicate there were mixed genetic structure and asymmetric contemporary gene flow within them. The ENMs revealed a similar demographic history for the three species expanded their ranges from the last interglacial (LIG) to the last glacial maximum (LGM), which was consistent with effective population sizes changes. Effects of genetic drift and fragmentation of habitats were responsible for the high differentiation and the lack of phylogeographic structure. Our results support that geological and climatic factors since Miocene triggered the differentiation, evolutionary origin and range shifts of the three oak species in the studied area and also emphasize that a multidisciplinary approach combining molecular markers, ENMs and population genetics can yield deep insights into diversification and evolutionary dynamics of species

Influence of angiotensin converting enzyme inhibitors/angiotensin receptor blockers on the risk of all‐cause mortality and other clinical outcomes in patients with confirmed COVID‐19: A systemic review and meta‐analysis

Abstract Since the COVID‐19 pandemic, physicians concerned about the potential adverse effects of angiotensin converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs). To explore the relationship between ACEIs/ARBs and the risk of mortality and other clinical outcomes in COVID‐19 patients, the authors conducted a systemic review and meta‐analysis. An electronic search was performed from inception to November 12, 2020 in PubMed, Medline, EMBASE, ClinicalTrials, TRIP, the Cochrane Library, CNKI, Wanfang, and CBM database. Risk of bias was assessed using the Risk Of Bias In Non‐randomized Studies of Interventions tool. The primary outcome was in‐hospital all‐cause mortality. Secondary outcomes included all‐cause mortality measured at 30‐day or longer term, mechanical ventilation, length of hospital stay, readmission, and cardiac adverse events. A total of 28 studies with 73 465 patients was included. Twenty‐two studies with 19 871 patients reported the incidence of all‐cause mortality. Results showed no association between using ACEIs/ARBs and risk of mortality crude odds ratio （OR） of 1.02, 95% CI 0.71–1.46, p = .90, I2 = 88%, adjusted OR in 6260 patients of 0.96, 95% CI 0.77–1.18, p = .68, I2 = 0%. While six studies with 10 030 patients reported a lower risk of mortality in ACEIs/ARBs group hazard ratio (HR) of 0.53, 95% CI 0.34–0.84, p = .007, I2 = 68%. Similar association (for HR) was found in hypertension subgroup. There was no significant association for the secondary outcomes. Based on the available data, we concluded that ACEIs/ARBs is not associated with the risk of in‐hospital all‐cause mortality in COVID‐19 patients, but may be associated with a decreased risk of 30‐day all‐cause mortality. Patients with hypertension may benefit from using ACEIs/ARBs