Hepatoprotective effects and mechanistic basis of cinnamaldehyde in preclinical liver disease models: A systematic review.

Progress in research on the hepatoprotective effects of C-21 steroidal glycosides from Baishouwu.

Hepatic encephalopathy (HE) associated with liver failure is accompanied by hyperammonemia, severe inflammation, depression, anxiety, and memory deficits as well as liver injury. Recent studies have focused on the liver-brain-inflammation axis to identify a therapeutic solution for patients with HE. Lipocalin-2 is an inflammation-related glycoprotein that is secreted by various organs and is involved in cellular mechanisms including iron homeostasis, glucose metabolism, cell death, neurite outgrowth, and neurogenesis. In this study, we investigated that the roles of lipocalin-2 both in the brain cortex of mice with HE and in Neuro-2a (N2A) cells. We detected elevated levels of lipocalin-2 both in the plasma and liver in a bile duct ligation mouse model of HE. We confirmed changes in cytokine expression, such as interleukin-1β, cyclooxygenase 2 expression, and iron metabolism related to gene expression through AKT-mediated signaling both in the brain cortex of mice with HE and N2A cells. Our data showed negative effects of hepatic lipocalin-2 on cell survival, iron homeostasis, and neurite outgrowth in N2A cells. Thus, we suggest that regulation of lipocalin-2 in the brain in HE may be a critical therapeutic approach to alleviate neuropathological problems focused on the liver-brain axis.

Portal-systemic collaterals and hepatic encephalopathy

From the Editor’s Desk…

Protective effects of Tinospora cordifolia miers extract against hepatic and neurobehavioral deficits in thioacetamide-induced hepatic encephalopathy in rats via modulating hyperammonemia and glial cell activation

Correction

Hepatoprotective and neuroprotective effects of quinacrine against bile duct ligation-induced hepatic encephalopathy in rats: Role of bone morphogenetic proteins signaling

SIRT1 alleviates hepatic ischemia-reperfusion injury via the miR-182-mediated XBP1/NLRP3 pathway

Pathogenesis of Liver Injury in Acute Liver Failure

Traditional Chinese patent medicine (TCPM) is widely used for essential hypertension (EH) in China. However, there is no critically appraised evidence, such as systematic reviews or meta-analyses, regarding the potential benefits and disadvantages of TCPM to justify their clinical use and recommendation. The aim of this review was to systematically evaluate and meta-analyze the effects of TCPM for EH.Seven databases, the Cochrane Library, PubMed, EMBASE, the China National Knowledge Infrastructure, the Chinese Scientific Journal Database, the Chinese Biomedical Literature Database, and the Wanfang Database, were searched from their inception to August 2014 for relevant studies that compared one TCPM plus antihypertensive drugs versus antihypertensive drugs alone. The methodological quality of the included trials was assessed using the Cochrane risk-of-bias tool. The primary outcome measures were mortality or progression to severe complications and adverse events. The secondary outcome measures were blood pressure (BP) and quality of life (QOL).Seventy-three trials, which included 8138 patients, on 17 TCPMs were included. In general, the methodological quality was low. Two trials evaluated the effects of TCPMs on mortality and the progression to severe complications after treatment, and no significant difference was identified compared with antihypertensive drugs alone. No severe adverse events were reported. Thirteen TCPMs used in complementary therapy significantly decreased systolic BP by 3.94 to 13.50 mmHg and diastolic BP by 2.28 to 11.25 mmHg. QOL was significantly improved by TCPM plus antihypertensive drugs compared with antihypertensive drugs alone.This systematic review provided the first classification of clinical evidence for the effectiveness of TCPM for EH. The usage of TCPMs for EH was supported by evidence of class level III. As a result of the methodological drawbacks of the included studies, more rigorously designed randomized controlled trials that focus on mortality and cardiovascular events during long-term follow-up are warranted before TCPM can be recommended for hypertensive patients. Two TCPMs, Song ling xue mai kang capsules and Yang xue qing nao granules, should be prioritized for further research.

Liver Injury Associated With Drugs and Complementary and Alternative Medicines in India

Tanshinone ⅡA (Tan ⅡA) is a monomer extracted from Salvia miltiorrhiza Bunge. Animal studies have demonstrated its potential in providing cognitive protection in Alzheimer's disease (AD), but the overall effects remain inconclusive, and its multiple mechanisms have not been systematically summarized. This systematic review and meta-analysis (SR/MA) aimed to evaluate the overall effects of Tan ⅡA on cognitive function in AD animal models and to summarize the mechanisms. Seven databases (PubMed, Embase, Web of Science, China National Knowledge Infrastructure, Chinese Biological Medical Disc, Chongqing VIP, and Wanfang databases) and grey literature were retrieved. Risk of bias was evaluated following the Systematic Review Center for Laboratory Animal Experiments. The mean difference (MD) or standard mean difference (SMD) with 95% confidence intervals (CIs) were used to evaluate the effect of Tan ⅡA on cognitive function, neuropathology, neuroinflammation, oxidative stress, apoptosis, and neural/synaptic plasticity, with P < 0.05 considered a significant difference. The effect and potential mechanisms of Tan ⅡA were demonstrated by performing multiple subgroup analyses. Nineteen studies involving 581 AD animals were identified. The included studies showed satisfactory reporting quality but had certain risks of bias in methodology. Tan ⅡA ameliorated cognitive deficits, evidenced by reducing escape latency (MD = -17.94 s; 95% CI: -22.92 to -12.96) and increasing time spent in the target quadrant (MD = 10.69 s; 95% CI: 7.32-14.07). It attenuated neuropathological damage by reducing amyloid-β (Aβ) plaques in thioflavine S staining (SMD = -3.46; 95% CI: -5.65 to -1.26) and increasing neuronal density in Nissl staining (SMD = 2.82; 95% CI: 2.11-3.52) and NeuN staining (SMD = 2.89; 95% CI: 1.71-4.08). Tan ⅡA also demonstrated anti-inflammatory effects through downregulation of pro-inflammatory cytokines [tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6)] and antioxidant stress properties by increasing superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) levels while reducing reactive oxygen species (ROS) and malondialdehyde (MDA) levels. Additionally, it exhibited antiapoptotic effects by increasing the B-cell lymphoma-2/Bcl-2-associated X protein (Bcl-2/Bax) ratio and decreasing Caspase-3 expression. Moreover, treatment improved neuronal/synaptic plasticity by upregulating postsynaptic density-95 (PSD-95) and brain-derived neurotrophic factor (BDNF) levels. Tan ⅡA could improve cognitive function and neuropathology through multiple mechanisms. This suggests that Tan IIA may serve as a viable candidate for the development of therapeutic strategies for AD. https://www.crd.york.ac.uk/PROSPERO/view/CRD42024588415.

HE liver plays a key role in the synthesis of proteins, metabolism of toxins and drugs, and in modulation of immunity. In critically ill patients, hypoxic, toxic, and inflammatory insults can affect hepatic excretory, synthetic, and/or purification functions, leading to systemic complications such as coagulopathy, increased risk of infection, hypoglycemia, and acute kidney injury. In severe cases, hepatic encephalopathyorbraindysfunction(acuteliverfailure)may occur. Because of the lack of specificity of standard laboratory investigations, identifying liver injury or dysfunction in critically ill patients remains a significant challenge. In addition, the great heterogeneity of criteria used to define the consequences of liver insults increases the difficulties for the clinician to properly interpret hepatic biochemical abnormalities. In this review, we choose to defineliver injuryas an elevation in serum concentrations of routinely measured hepatic enzymes, including aminotransferases (aspartate aminotransferase [AST]; alanine aminotransferase, [ALT]), alkaline phosphatase (ALP), or!-glutamyl transpeptidase. Hepatic dysfunctionrefers to derangement of pathways related to synthetic or clearance function, including international normalized ratio (INR) and bilirubin.Hepatotoxicity refers to hepatic injury and dysfunction caused by a drug or another noninfectious agent. 1 Acute liver failuredesignates

Objective: To determine whether nasal submucosal injection of low-concentration epinephrine improved the surgical field visualization and physician satisfaction compared to placebo or without intervention. Methods: A literature search of PubMed, Scopus, Web of Science, Cochrane library, China National Knowledge Infrastructure, and Wanfang Database was conducted from inception to January 10, 2023. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Meta-analyses were performed using Review Manager (RevMan version 5.3; the Cochrane Collaboration). Quality was assessed by 2 reviewers using the Cochrane Risk of Bias Tool. And we used funnel plots to visually assess the risk of publication bias. Results: We included a total of 11 studies with 492 patients, all of which were randomized controlled trials. Among the studies, 4 had a low risk of bias, 4 had a moderate risk of bias, and 3 had a high risk of bias. Five studies reported visual bleeding grade in the surgical field (P = 0.07) and total blood loss (P = 0.16), 8 studies reported preoperative baseline heart rate (P = 0.58) and baseline mean arterial pressure (MAP) (P = 0.78), and 9 studies reported intraoperative heart rate (P = 0.27) and MAP (P = 0.56), which showed no significant differences in these parameters between the 2 groups. None of these outcomes were statistically significant between the epinephrine group and the control group. Conclusion: There is insufficient evidence to support the nasal submucosal application of low-concentration epinephrine to improve surgical field dryness and reduce total surgical bleeding.

The BH3-Only Protein Bid Does Not Mediate Death-Receptor-Induced Liver Injury in Obstructive Cholestasis