Yinhuang granule alleviates carbon tetrachloride-induced liver fibrosis in mice and its mechanism.

BACKGROUND: Liver fibrosis is a formidable global medical challenge, with no effective clinical treatment currently available. Yinhuang granule (YHG) is a proprietary Chinese medicine comprising Scutellariae Radix and Lonicerae Japonicae Flos. It is frequently used for upper respiratory tract infections, pharyngitis, as well as acute and chronic tonsillitis. AIM: To investigate the potential of YHG in alleviating carbon tetrachloride (CCl4)-induced liver fibrosis in mice. METHODS: To induce a hepatic fibrosis model in mice, this study involved intraperitoneal injections of 2 mL/kg of CCl4 twice a week for 4 wk. Meanwhile, liver fibrosis mice in the low dose of YHG (0.4 g/kg) and high dose of YHG (0.8 g/kg) groups were orally administered YHG once a day for 4 wk. Serum alanine/aspartate aminotransferase (ALT/AST) activity and liver hydroxyproline content were detected. Sirius red and Masson's trichrome staining assay were conducted. Real-time polymerase chain reaction, western-blot and enzyme-linked immunosorbent assay were conducted. Liver glutathione content, superoxide dismutase activity level, reactive oxygen species and protein carbonylation amount were detected. RESULTS: The administration of YHG ameliorated hepatocellular injury in CCl4-treated mice, as reflected by decreased serum ALT/AST activity and improved liver histological evaluation. YHG also attenuated liver fibrosis, evident through reduced liver hydroxyproline content, improvements in Sirius red and Masson's trichrome staining, and lowered serum hyaluronic acid levels. Furthermore, YHG hindered the activation of hepatic stellate cells (HSCs) and ameliorated oxidative stress injury and inflammation in liver from CCl4-treated mice. YHG prompted the nuclear accumulation of nuclear factor erythroid 2-related factor 2 (Nrf2) and upregulated the expression of Nrf2-dependent downstream antioxidant genes. In addition, YHG promoted mitochondrial biogenesis in liver from CCl4-treated mice, as demonstrated by increased liver adenosine triphosphate content, mitochondrial DNA levels, and the expression of peroxisome proliferator-activated receptor gamma coactivator 1 alpha and nuclear respiratory factor 1. CONCLUSION: YHG effectively attenuates CCl4-induced liver fibrosis in mice by inhibiting the activation of HSCs, reducing inflammation, alleviating liver oxidative stress damage through Nrf2 activation, and promoting liver mitochondrial biogenesis.

Positively Charged Silver and Gold Nanoparticles with Controllable Size Distribution for SERS Detection of Negatively Charged Molecules.

Surface-enhanced Raman spectroscopy (SERS) has been demonstrated as an ultrasensitive tool for various molecules. However, for the negatively charged molecules, the widely used SERS substrate [negatively charged Ag and Au nanoparticles (Ag or Au NPs (-)] showed either low sensitivity or poor stability. The best solution is to synthesize positively charged silver or gold nanoparticles [Ag or Au NPs (+)] with high stability and excellent SERS performance, which are currently unavailable. To this end, we revitalized the strategy of "charge reversal and seed growth". By selection of ascorbic acid as the reductant and surfactant, the surface charge of Ag or Au NP (-) seeds is adjusted to a balanced state, where the surface charge is negative enough to satisfy the stabilization of the NPs (-) but does not hinder the subsequent charge reversal. By optimization of the chain length and electric charge of polyamine molecules, the highly stable and size-controllable uniform Ag NPs (+) and Au NPs (+) were seed-growth synthesized with high reproducibility. More importantly, the SERS performance of both Ag NPs (+) and Au NPs (+) achieved the trace detection of negatively charged molecules at the level of 1 µg/L, demonstrating an improved SERS sensitivity of up to 3 orders of magnitude compared to the previously reported sensitivity. Promisingly, the introduction of polyamine-capped Ag NPs (+) and Au NPs (+) as SERS substrates with high stability (1 year shelf life) will significantly broaden the application of SERS.

Circulating cytokines and alcoholic liver disease: a two-sample bidirectional Mendelian randomization study.

BACKGROUND: Increased inflammation in the liver during ethanol exposure is a major feature of alcoholic liver disease (ALD). An important contributing component to the development of ALD is the inflammatory response brought on by immunological response, however the connection between individual circulating cytokines and ALD is still unclear. To ascertain the causation, we conducted a two-sample bidirectional Mendelian randomization research. METHODS: We extracted 41 cytokines and growth factors of 8293 Europeans and ALD cases of the same ethnicity (1416 cases and 217,376 controls) from the Genome-Wide Association Studies (GWAS) database for two-sample bidirectional MR analysis. RESULTS: Our analyses suggest that higher interleukin-7 (IL-7) levels are associated with an increased risk of ALD (p = 0.028, OR = 1.191,95% CI = 1.019-1.392), while tumor necrosis factor related apoptosis inducing ligand (TRAIL) is a protective factor for ALD (p = 0.032, OR = 0.863, 95% CI = 0.754-0.988) which can reduce the risk of disease occurrence. In addition, genetically predicted ALD does not affect the expression of circulating cytokines regulators. CONCLUSIONS: Our study supports that cytokines play a pivotal role in the pathogenesis of ALD. To determine the mechanisms and pathways of action of these biomarkers, further basic research is required to ensure their clinical suitability for preventing and treating ALD.

Environmental exposure to organophosphate esters and suspected non-alcoholic fatty liver disease among US adults: A mixture analysis.

Objectives: Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide. We evaluated NAFLD using the US FLI to determine whether there is an association between urinary organophosphorus (OPE) levels and the "prevalence" of NAFLD in US individuals. Methods: The current study included 1,102 people aged 20 years and older with information from the 2011-2014 U.S. National Health and Nutrition Examination Survey. NAFLD was assessed using the U.S. FLI. Individual OPE metabolites and OPE combinations were linked to NAFLD using logistic regression and weighted quantile sum (WQS) regression. All analyzes were carried out separately on males and females. The possible impacts of age, serum total testosterone (TT), and menopausal state, as well as the importance of the interaction term with exposure, were investigated using stratified analysis. Results: Bis (2-chloroethyl) phosphate and bis (1,3-dichloro-2-propyl) phosphate were associated with NAFLD in all males after adjusting for covariates (P < 0.05). A combination of OPEs (OPE index) was positively linked with NAFLD in the WQS analysis of all males (odds ratio for OPE index: 1.52; 95% CI: 1.06, 2.19). Stratified analyzes for males revealed that considerable connections were largely confined to individuals over 60 years old or with low total testosterone. In women, the connection was limited and inconsistent, except for the OPE index, which was positively linked with NAFLD in post-menopausal women. Conclusions: In this study, environmental exposure to OPE was linked to an elevated risk of NAFLD in males, particularly those over 60 years old or with low TT levels. Aside from the continuous positive connection of a combination of OPEs with NAFLD risk in post-menopausal women, these correlations were weaker in women. However, these findings should be taken with caution and verified in future investigations by collecting numerous urine samples in advance to strengthen OPE exposure estimates.

Qualitative analysis of trace quinolone antibiotics by SERS with fine structure dependent sensitivity.

Antibiotics are widely used in daily life, which has created a global scenario where many pathogenic organisms have become effectively resistant to antibiotics. The abuse or overuse of antibiotics causes significant environmental pollution and even endangers human health. It is well-known that antibiotics' efficacy (toxicity) is determined by molecular structure. Therefore, structure-level qualitative analysis with high sensitivity and accuracy is vitally important. Characterized by fingerprinting recognition, Raman spectroscopy, especially surface-enhanced Raman spectroscopy (SERS), has become an essential qualitative analysis tool in various fields, such as environmental monitoring and food safety. With the exception of chirality, this study completed the qualitative trace analysis of 16 quinolone antibiotics (QNs) with fine molecular structure differences using SERS. The sensitivity was tuned in by one order of magnitude through the different electronegativity and steric hindrances of the slightly changed functional groups in the specific antibiotics. The fine structure dependent sensitivity enables SERS to be a powerful on-site monitoring tool to control the abuse of antibiotics with high toxicity; thus, decreasing the subsequent risk to the environmental ecology and human society.

Revealing the synergistic effect of capillary force and electrostatic attraction for D-SERS sensitivity.

To overcome the relative weak stability and reproducibility of solid substrates and the long no-signal duration before the short signal-on period of dynamic SERS (D-SERS) strategies, we introduced an electrostatic attraction between the molecule and the D-SERS substrate. The synergistic effect between capillary force and electrostatic attraction during D-SERS measurements improves the SERS sensitivity by 2-3 orders of magnitude compared to that for a solid SERS substrate prepared via liquid-liquid interface self-assembly.

Synthesis of benzoxazoles via an iron-catalyzed domino C-N/C-O cross-coupling reaction.

An eco-friendly and efficient method has been developed for the synthesis of 2-arylbenzoxazoles via a domino iron-catalyzed C-N/C-O cross-coupling reaction. Some of the issues typically encountered during the synthesis of 2-arylbenzoxazoles in the presence of palladium and copper catalysts, including poor substrate scope and long reaction times have been addressed using this newly developed iron-catalyzed method.

Method for the Synthesis of Phenothiazines via a Domino Iron-Catalyzed C-S/C-N Cross-Coupling Reaction.

An environmentally benign and efficient method has been developed for the synthesis of phenothiazines via a tandem iron-catalyzed C-S/C-N cross-coupling reaction. Some of the issues typically encountered during the synthesis of phenothiazines in the presence of palladium and copper catalysts, including poor substrate scope, long reaction times and poor regioselectivity, have been addressed using this newly developed iron-catalyzed method.