Polyoxometalate-Intercalated Tremella-Like CoNi-LDH Nanocomposites for Electrocatalytic Nitrite-Ammonia Conversion.

The electrocatalytic reduction of NO2- (NO2RR) holds promise as a sustainable pathway to both promoting the development of emerging NH3 economies and allowing the closing of the NOx loop. Highly efficient electrocatalysts that could facilitate this complex six-electron transfer process are urgently desired. Herein, tremella-like CoNi-LDH intercalated by cyclic polyoxometalate (POM) anion P8W48 (P8W48/CoNi-LDH) prepared by a simple two-step hydrothermal-exfoliation assembly method is proposed as an effective electrocatalyst for NO2- to NH3 conversion. The introduction of POM with excellent redox ability tremendously increased the electrocatalytic performance of CoNi-LDH in the NO2RR process, causing P8W48/CoNi-LDH to exhibit large NH3 yield of 0.369 mmol h-1 mgcat-1 and exceptionally high Faradic efficiency of 97.0% at -1.3 V vs the Ag/AgCl reference electrode in 0.1 M phosphate buffer saline (PBS, pH = 7) containing 0.1 M NO2-. Furthermore, P8W48/CoNi-LDH demonstrated excellent durability during cyclic electrolysis. This work provides a new reference for the application of POM-based nanocomposites in the electrochemical reduction of NO2- to obtain value-added NH3.

Multi-technology integrated network pharmacology-based study on phytochemicals, active metabolites, and molecular mechanism of Psoraleae Fructus to promote melanogenesis.

ETHNOPHARMACOLOGICAL RELEVANCE: According to the Compendium of Materia Medica (Shizhen Li, Ming dynasty) and Welfare Pharmacy (Song dynasty), Psoraleae Fructus (PF), a traditional Chinese medicine (TCM) has a bitter taste and warm nature, which has the effect of treating spleen and kidney deficiency and skin disease. Although PF has been widely used since ancient times and has shown satisfactory efficacy in treating vitiligo, the active substances and the mechanism of PF in promoting melanogenesis remain unclear. AIM OF THE STUDY: To explore the active substances and action mechanisms of PF in promoting melanogenesis. MATERIALS AND METHODS: Firstly, UPLC-UV-Q-TOF/MS was used to characterize the components in PF extract and identify the absorption components and metabolites of PF after oral administration at usual doses in rats. Secondly, the active substances and related targets and pathways were predicted by network pharmacology and molecular docking. Finally, pharmacodynamic and molecular biology experiments were used to verify the prediction results. RESULTS: The experimental results showed that 15 compounds were identified in PF extract, and 44 compounds, consisting of 8 prototype components and 36 metabolites (including isomers) were identified in rats' plasma. Promising action targets (MAPK1, MAPK8, MAPK14) and signaling pathways (MAPK signaling pathway) were screened and refined to elucidate the mechanism of PF against vitiligo based on network pharmacology. Bergaptol and xanthotol (the main metabolites of PF), psoralen (prototype drug), and PF extract significantly increased melanin production in zebrafish embryos. Furthermore, bergaptol could promote the pigmentation of zebrafish embryos more than psoralen and PF extract. Bergaptol significantly increased the protein expression levels of p-P38 and decreased ERK phosphorylation in B16F10 cells, which was also supported by the corresponding inhibitor/activator combination study. Moreover, bergaptol increased the mRNA expression levels of the downstream microphthalmia-associated transcription factor (MITF) and tyrosinase in B16F10 cells. Our data elucidate that bergaptol may promote melanogenesis by regulating the p-P38 and p-ERK signaling pathway. CONCLUSIONS: This study will lay a foundation for discovering potential new drugs for treating vitiligo and provide feasible ideas for exploring the mechanism of traditional Chinese medicine.

In Situ Implantation of Chitosan Oligosaccharide-Doped Lipoic Acid Hydrogel Breaks the "Vicious Cycle" of Inflammation and Residual Tumor Cell for Postoperative Skin Cancer Therapy.

Surgical excision is the main treatment for skin cancer, but the tumor recurrence caused by the "vicious cycle" between residual tumor cells and postoperative inflammation remains a challenge. Herein, a new material, which can break the "vicious cycle", was developed by incorporating chitosan oligosaccharides into lipoic acid hydrogel (COS@LA-hydrogel). When implanted at the resection site, the COS@LA-hydrogel would have a sustained release of LA and COS, which could not only kill residual tumor cells by synergistically reducing AKT phosphorylation but also decrease inflammation by inhibiting the expression of tumor necrosis factor-α (TNF-α) and inhibiting bacterial infection, respectively. As a proof of concept, in the postoperative melanoma resection model, the COS@LA-hydrogel reduced the expression of pro-inflammatory factors TNF-α and interleukin-6 (IL-6) by up to 78 and 80%, respectively, and they showed almost no tumors and the median survival of the mice was 2.5 times longer than that of the control group. The hydrogel with the function of "vicious cycle" breaking holds clinical potential.

Prediction of no reflow phenomenon in percutaneous coronary intervention with optical coherence tomography and analysis of risk factors.

Objective :To investigate the predictive value of no reflow phenomenon in interventional therapy by measuring plaque quantitatively with optical coherence tomography (OCT).  Methods:196 patients with acute ST segment elevation myocardial infarction who visited the Department of Cardiology of the Second Affiliated Hospital of Zhengzhou University from January 2020 to January 2022 were selected as the study objects. According to whether there was no reflow during the operation, they were divided into no reflow group (46 cases) and normal flow group (150 cases). Systematically collect general clinical data and coronary angiography related data of patients through inpatient cases, measure fiber cap thickness and lipid core angle of diseased vascular plaque through optical coherence tomography, and analyze the relationship between fiber cap thickness and no reflow phenomenon   Results:BMI, LDL, phospholipase A, the proportion of family history of coronary heart disease, and the thrombus load in the no reflow group were higher than those in the normal flow group (P<0.05), while the thickness of the fibrous cap was lower than that in the normal flow group (P<0.05); Further multivariate logistic regression analysis showed that fiber cap thickness, phospholipase A and severe thrombosis load were independent risk factors for non reflow phenomenon (P<0.05); Further ROC curve analysis found that the thickness of fiber cap had a high predictive value for no reflow phenomenon, and the best cutoff value for no reflow was 95, AUC: 0.926 (95% CI: 0.891-0.961, P<0.001). Conclusions: Optical coherence tomography can predict the occurrence of no reflow phenomenon by measuring the fiber cap thickness quantitatively. The prediction effect is the best when the fiber cap thickness is 95.

Simultaneous online SPE-HPLC-MS/MS quantification of gefitinib, osimertinib and icotinib in dried plasma spots: Application to therapeutic drug monitoring in patients with non-small cell lung cancer.

Gefitinib, osimertinib and icotinib are the most commonly used tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC) with EGFR mutation. Therapeutic drug monitoring (TDM) for these TKIs has become a standard and essential procedure. Dried plasma spots (DPS) was choosen for microsampling strategies for TDM, allowing easy and cost-effective logistics in many settings. This study developd and validated an assay for the simultaneous quantitative determination of gefitinib, osimertinib and icotinib in DPS by online solid-phase extraction-liquid chromatography-tandem mass spectrometry (online SPE-LC-MS) system. The TKIs were extracted from DPS with methanol and enriched on a Welch Polar-RP SPE column (30 × 4.6 mm, 5 µm), followed by separation on Waters X Bridge C18 analytical column(4.6 × 100 mm, 3.5 µm). The method achieved LLOQ of 2 ng mL-1 for gefitinib and osimertinib (4 ng mL-1 for icotinib), respectively (r2 > 0.99). Precision (within-run 1.54-7.41 % RSD; between-run 3.03-12.84 % RSD), accuracy (range from 81.47 % to 105.08 %; between-run bias 87.87-104.13 %). Osimertinib and icotinib were stable in DPS stored at - 40 °C for 30 days, 4 °C, 42 °C and 60 °C for 5 days and well-sealed 37 °C,75 % humidity (except gefitinib). Lastly, the assay was applied to TDM of TKIs in 46 patients and the results were compared to SALLE assisted LC-MS analysis, it could be confirmed that the developed method achieves similarly good results as the already established one and no bias could be detected. It implies that this method capable of supporting clinical follow-up TDM of TKIs in DPS from poor medical environment.

A comprehensive quality control evaluation for standard decoction of Smilax glabra Roxb based on HPLC-MS-UV/CAD methods combined with chemometrics analysis and network pharmacology.

An effective, sensitive, and rapid method was developed for the quality control evaluation of the standard decoction of Smilax glabra Roxb (SGR). SGR is a primary ingredient of the traditional functional foods of turtle jelly and SGR tea. Chemometrics, Network Pharmacology, and molecular docking were used to screen for six quality markers. Multiple extraction parameters were optimized. HPLC-UV/CAD-QAMS was used to rapidly quantify the six quality markers (neoastilbin, astilbin, neoisoastilbin, isoastilbin, quercitrin, and isoengeletin) in 10 batches of the standard decoction of SGR samples. The relative correction factor (RCF) values of the five compounds were close to 1, demonstrating that the charged aerosol detection (CAD) showed a consistent response to compounds with similar parent nucleus structures. This method can serve as a guide for rapid quantitative analysis of the multi-components of the SGR standard decoction and all the traditional functional foods of turtle jelly with the homology of medicine.

Scavenging ROS and inflammation produced during treatment to enhance the wound repair efficacy of photothermal injectable hydrogel.

Injectable hydrogels with near infrared (NIR) photothermal ability show attractive application prospects in the treatment of wound infection and promoting skin defect repair. Nevertheless, excess reactive oxygen species (ROS) and inflammatory responses caused by bacterial infection and photothermal therapy (PTT) would delay tissue regeneration and wound healing. In this study, a novel NIR photothermal injectable hydrogel with anti-oxidation and anti-inflammation by incorporating α-lipoic acid modified palladium nanoparticles into calcium ions crosslinked sodium alginate hydrogel was developed. The resulting hydrogel facilitated to fill perfectly various irregular wounds, and could convert NIR light into local high-heat to kill >80 % of Escherichia coli and Staphylococcus aureus. Remarkably, the hydrogel exhibited excellent anti-oxidant and anti-inflammatory activity, which could scavenge >60 % of ROS in cells and decrease the relative expression level of tumor necrosis factor-alpha and interleukin-1ß genes by 52.9 % and 53.3 % respectively. It was found that the NIR photothermal injectable hydrogel with anti-oxidation and anti-inflammation could effectively reduce ROS and inflammation caused by bacterial infection and PPT. Additionally, it could also enhance wound repair efficiency. The hydrogel is expected to be a potential wound dressing for the treatment of clinical skin defects.

Survival Outcome of Salivary Gland Carcinoma: A 50-Year Retrospective Study With Long-Term Follow-up.

PURPOSE: Salivary gland carcinomas (SGCs) can be classified into more than 20 subtypes with various clinical behaviors. The present study aimed to analyze the clinical and pathological features of SGCs and evaluate their long-term prognosis. METHODS: A retrospective cohort study was performed. This study investigated cases of histologically confirmed SGC at the authors' institution from January 1963 to December 2014. Data on sex, age, site, histopathological diagnosis, tumor-node-metastasis classification, postoperative radiotherapy and/or chemotherapy, local and regional recurrence, and distant metastasis (DM) were collected as covariates. The overall survival (OS) rate was analyzed as the outcome. Kaplan-Meier survival analysis and Cox multivariate analysis were used for survival analysis. The cohort was divided into 2 groups-before and after 1989. The clinicopathological characteristics of the 2 groups were compared using the χ2 test. RESULTS: The cohort included 1,637 patients who met the admission criteria and had a male-to-female ratio of 0.9:1. The median age was 47 years (range, 8 months to 86 years). The median follow-up time was 54 months (range, 1-432 months). The majority of the tumors occurred in the parotid gland (35.3%), followed by the palate gland (25.2%). Adenoid cystic carcinoma was the most common tumor type (34.3%), and mucoepidermoid carcinoma (29%) was the second most common type. In the 1,637 patients, the neck lymph node metastasis rate was 8.7% at the first surgery, and the overall DM rate was 14.1%. The 5-, 10-, and 15-year OS rates of the 1,637 cases were 93.1%, 87.2%, and 79.3%, respectively. Comparative analysis before and after 1989 showed statistically significant differences in sex, site, histologic subtype, T classification, local and regional recurrence rate, and radiotherapy (P < .05), while no significant differences were found in age, N classification, M staging, DM, or chemotherapy. CONCLUSIONS: The OS rates of SGC have improved significantly over the past 30 years. This is attributable to an increase in the proportion of patients diagnosed at the early stage and receiving radiotherapy, as this has led to a reduction in the local and regional recurrence rate and, consequently, an improvement in the survival rates.

Identification of bicyclol metabolites in rat plasma, urine and feces by UPLC-Q-TOF-MS/MS and evaluation of the efficacy and safety of these metabolites based on network pharmacology and molecular docking combined with toxicity prediction.

Bicyclol (BIC) has been widely used to treat drug-induced liver injury (DILI), however, it still has the problems of low solubility and bioavailability. Besides, the metabolic characteristics of BIC remain unclear. In the current study, we identified the metabolite of BIC in rat plasma, urine and feces, and evaluated the efficacy and safety of these metabolites. Based on the fragmentation behavior, we totally identified 11 metabolites and 7 metabolites in plasma, 8 metabolites in urine and 8 metabolites in feces. Notably, M1-M3, M6, M7, M10 and M11 were identified for the first time. M7 was the most abundant metabolite in the rat plasma. The metabolic pathways mainly involved demethylation, dealkylation, hydrolysis, methylation, oxidation and glucuronidation. In addition, the efficacy and safety of BIC's metabolites were evaluated by network pharmacology and molecular docking combined with toxicity prediction. The analysis of network pharmacology indicated that BIC's metabolites against DILI through the MAPK signaling pathway and Hepatitis B pathway. The molecular docking results showed that the binding energy of 5 compounds that docked with "7nuw" and 10 compounds that docked with "4tjz" was lower than BIC. 11 compounds possessed higher solubility and lower toxicity than BIC in prediction. Thus, the identification and evaluation of BIC's metabolites contributed to a better understanding of pharmacological mechanism of BIC and the high-value metabolites of high efficacy, safety and solubility provided a basis for drug development.

Post-COVID pain and quality of life in COVID-19 patients: protocol for a meta-analysis and systematic review.

INTRODUCTION: During the COVID-19 pandemic, approximately 10%-35% of COVID-19 infected patients experience post-COVID sequela. Among these sequelae, pain symptoms should not be neglected. In addition, the sequelae of COVID-19 also decrease the quality of life of these populations. However, meta-analyses that systematically evaluated post-COVID pain are sparse. METHODS AND ANALYSIS: A comprehensive screening will be performed by searching MEDLINE and Embase without language restriction from inception to August 2021. Cohort studies, case-control studies, cross-sectional studies and case series will be included. Case report and interventional studies will be excluded. Studies with less than 20 participants will be also excluded. We aim to investigate the prevalence of pain-related symptoms in patients after the acute phase of COVID-19. The impact of COVID-19 on the quality of life and pain symptoms among these populations in the post-acute phase will also be evaluated. ROBINS-I tool will be used to assess the risk of bias of cohort studies. The risk of bias tool developed by Hoy et al will be used to assess the risk of bias of prevalence studies. Metaprop command in Stata will be used to estimate the pooled prevalence of pain symptoms. DerSimonian and Laird random-effects models will be used to calculate the pooled relative risks. All analyses will be calculated using Stata software (V.15.0; StataCorp) ETHICS AND DISSEMINATION: Ethics approval is not required. Results of our study will be submitted to a peer-review journal. PROSPERO REGISTRATION NUMBER: CRD42021272800.

In-situ synthesis silver nanoparticles in chitosan/Bletilla striata polysaccharide composited microneedles for infected and susceptible wound healing.

A novel antibacterial strategy is urgently required to develop for solving bacterial biofilm obstruction and bacterial drug resistance in the infected wound healing process. Herein, the Chitosan/Bletilla striata polysaccharide composited microneedles were prepared by chitosan, tannic acid, AgNO3 and Bletilla striata polysaccharide through step centrifugation. In our design system, the porous structure of microneedles gradually disappeared, and the mechanical properties were significantly improved after multiple fillings. Ag+ is reduced in-situ to silver nanoparticles by the abundant polyphenols of tannic acid, displaying antibacterial effects both in vitro and vivo, even for methicillin resistant Staphylococcus aureus. The addition of Bletilla striata polysaccharide increased the ability of piercing biofilm and promoted wound healing. The microneedles exhibited good biocompatibility and with function of piercing the bacterial biofilms, scavenging excessive free radicals, inhibiting inflammatory factors, and promoting wound healing. Therefore, the multifunctional composited microneedles show great potential to promote infected and susceptible wound healing.

Experimental and modeling evidence of hydroxyl radical production in iron electrocoagulation as a new mechanism for contaminant transformation in bicarbonate electrolyte.

Iron electrocoagulation is designed for sustainable high-efficiency and high-flexibility water purification applications. Recent advances reported that hydroxyl radicals (•OH)-based oxidative transformation of organic contaminants can occur in iron electrocoagulation. However, there is still a lack of mechanistic understanding the production of •OH in bicarbonate electrolyte, which presents a critical knowledge gap in the optimization of iron electrocoagulation technology towards practical application. Combined with contaminant degradation, radical quenching experiments, and spectroscopic techniques, we found that •OH was produced at rate of 16.1 µM∙h - 1 during 30-mA iron electrocoagulation in bicarbonate electrolyte through activation of O2 by Fe(II) under pH-neutral conditions. High yield of •OH occurred at pH 8.5, likely due to high adsorbed Fe(II) that can activate O2 to enhance •OH production. Mössbauer and X-ray photoelectron spectroscopy measurements substantiated that Fe(II)-adsorbed lepidocrocite was the dominant solid Fe(II) species at pH 8.5. A process-based kinetic modeling was developed to describe the dynamic of •OH production, Fe(II) oxidation, and contaminant degradation processes in iron electrocoagulation. Findings of this study extend the functionality of electrocoagulation from phase separation to •OH-based advanced oxidation process, which provides a new perspective for the development of electrocoagulation-based next generation sustainable water purification technology.

AGR2-induced cholesterol synthesis drives lovastatin resistance that is overcome by combination therapy with allicin.

Anterior gradient 2 (AGR2), a protein disulfide isomerase (PDI), is a multifunctional protein under physiological and pathological conditions. In this study we investigated the roles of AGR2 in regulating cholesterol biogenesis, lipid-lowering efficiency of lovastatin as well as in protection against hypercholesterolemia/statin-induced liver injury. We showed that AGR2 knockout significantly decreased hepatic and serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) in mice with whole-body or hepatocyte-specific Agr2-null mutant, compared with the levels in their wild-type littermates fed a normal chow diet (NCD) or high-fat diet (HFD). In contrast, mice with AGR2 overexpression (Agr2/Tg) exhibited an increased cholesterol level. Mechanistic studies revealed that AGR2 affected cholesterol biogenesis via activation of AKT/sterol regulatory element-binding protein-2 (SREBP2), to some extent, in a PDI motif-dependent manner. Moreover, elevated AGR2 led to a significant decrease in the lipid-lowering efficacy of lovastatin (10 mg· kg-1· d-1, ip, for 2 weeks) in mice with hypercholesterolemia (hyperCho), which was validated by results obtained from clinical samples in statin-treated patients. We showed that lovastatin had limited effect on AGR2 expression, but AGR2 was inducible in Agr2/Tg mice fed a HFD. Further investigations demonstrated that drug-induced liver toxicity and inflammatory reactions were alleviated in hypercholesterolemic Agr2/Tg mice, suggesting the dual functions of AGR2 in lipid management and hyperCho/statin-induced liver injury. Importantly, the AGR2-reduced lipid-lowering efficacy of lovastatin was attenuated, at least partially, by co-administration of a sulfhydryl-reactive compound allicin (20 mg· kg-1· d-1, ip, for 2 weeks). These results demonstrate a novel role of AGR2 in cholesterol metabolism, drug resistance and liver protection, suggesting AGR2 as a potential predictor for selection of lipid-lowering drugs in clinic.

Peptide ligand-SiO2 microspheres with specific affinity for phosphatidylserine as a new strategy to isolate exosomes and application in proteomics to differentiate hepatic cancer.

Exosomes are membrane bound extracellular vesicles that play an important role in many biological processes. While they have great application value, exosome isolation is still considered a major scientific challenge. In the present study, a novel separation strategy for exosomes is proposed based on the specific interaction between immobilized peptide ligands and phosphatidylserine moieties which are highly abundant on the surface of exosomes. With the new affinity method, intact model exosomes can be recovered with a high yield in a short processing time. The purity of exosome samples enriched from serum by the affinity method is far higher than that isolated by ultrafiltration, and similar to that obtained by density gradient centrifugation and ultracentrifugation. Moreover, the variety of contaminants co-isolated by the affinity method is relatively low due to its specific separation principle. Proteomics analysis of exosomes isolated by the affinity method from the serum of healthy, hepatocellular carcinoma patients, and intrahepatic cholangiocarcinoma patients was performed to prove the applicability of this method. In conclusion, our novel strategy shows characteristics of easy preparation, high specificity, and cost-effectiveness, and provides a promising approach for exosome isolation which should have wide applications.

Schisandrol A, the main active ingredient of Schisandrae Chinensis Fructus, inhibits pulmonary fibrosis through suppression of the TGF-ß signaling pathway as revealed by UPLC-Q-TOF/MS, network pharmacology and experimental verification.

ETHNOPHARMACOLOGICAL RELEVANCE: Schisandra chinensis decoction derived from the book of Waitai Miyao (Tao Wang, Tang dynasty) is often used in the treatment of idiopathic pulmonary fibrosis (IPF), which is included in the Grand Ceremony of Chinese formulae (Huairen Peng, 1994). Schisandrae Chinensis Fructus (Sch) is one of the most important herbs in this formula. According to the "Shennong's Herbal Classicherbal" of the Han Dynasty, Sch has sour taste, warm nature, which has the effect of tonifying qi and curing cough. In addition, according to the "Compendium of Materia Medica" of the Ming Dynasty, Sch is used to treat cough and asthma, which has the effect of moistening the lung and tonifying the kidney. However, the active ingredients of Sch absorption into the plasma and its pharmacological mechanism of treatment for IPF still remained unclear. AIM OF THE STUDY: Our research aimed at identifying the absorbed active ingredients and metabolized of Sch in rat plasma and the mechanism of anti-IPF based on serum pharmacochemistry. MATERIALS AND METHODS: First, the rats were divided into control group and Sch group. Sch sample was orally administrated to the rats for seven days. The blood samples were drawn into an Eppendorf tube after the last dosing. The ultrahigh performance liquid chromatography coupled with quadrupole-time of flight mass spectrometry (UPLC-Q-TOF/MS) was applied to identify the absorption components and metabolites of Sch in rat plasma. Second, the network pharmacology combined with molecular docking analysis was further investigated to illuminate its potential mechanism of treatment for IPF by the biological targets regulating related pathways. Finally, the mechanism of action was verified by experimental in vitro and in vivo. RESULTS: A total of 78 compounds, consist of 13 prototype lignans and 65 metabolites (including isomers) were identified. Network pharmacology study and molecular docking analysis indicated that schisandrol A (L1) play an anti-fibrosis role by regulating the TGF-ß signaling pathway. Experimental in vitro and in vivo verified that the schisandrol A could inhibiting pulmonary fibrosis through TGF-ß signaling pathway. The effect and mechanism of schisandrol A inhibiting pulmonary fibrosis were reported for the first time. CONCLUSIONS: In this study, the absorption active ingredients of Sch in rat plasma were combined with the network pharmacology investigation and experimental in vitro and in vivo to elucidate its biological mechanism of treatment for IPF. The results provided a theoretical support for understanding the bioactive compounds and the pharmacological mechanism of Sch.

Baicalin Alleviates Thrombin-Induced Inflammation in Vascular Smooth Muscle Cells.

Atherosclerosis (AS) is a chronic inflammatory disease of the arterial intima. As AS represents the most common type of vascular disease, it affects millions of individuals and is a source of high morbidity and mortality rates worldwide. Overwhelming evidence indicates that AS-related inflammation is mediated by proinflammatory cytokines, chemokines, adhesion molecules and inflammatory signaling pathways, with each of these factors being shown to play critical roles during the entire progression of AS. While a number of drugs have been approved for use in the treatment of AS, their benefits are modest, which underscores the urgency for the development of new drug therapies. In part, these deficits in effective drugs can be attributable to the lack of a clear understanding of the molecular mechanisms of AS. In this study, we investigate the capacity for thrombin to trigger inflammation and induce cell proliferation in vascular smooth muscle cells (VSMCs). We then assessed the effects of baicalin and its potential mechanisms on VSMC inflammation as induced by thrombin. Baicalin, which is a natural bioactive compound of S. baicalensis Georgi (SBG), exerted a protective effect against thrombin-induced VSMC inflammation as resulting from the upregulation of PAR-1. This protection as exerted by baicalin appears to reside in its capacity to produce an inhibitory effect on the thrombin-induced activation of the ERK1/2 pathway. These findings suggest that baicalin may be a promising candidate for the treatment of atherosclerosis.

Anterior gradient 2 increases long-chain fatty acid uptake via stabilizing FABP1 and facilitates lipid accumulation.

Anterior gradient 2 (AGR2), a protein disulfide isomerase (PDI), is a well-established oncogene. Here, we found that Agr2-/- mice had a decreased fat mass and hepatic and serum lipid levels compared with their wild-type littermates after fasting, and exhibited reduced high-fat diet (HFD)-induced fat accumulation. Transgenic mice overexpressing AGR2 (Agr2/Tg) readily gained fat weight on a HFD but not a normal diet. Proteomic analysis of hepatic samples from Agr2-/- mice revealed that depletion of AGR2 impaired long-chain fatty acid uptake and activation but did not affect de novo hepatic lipogenesis. Further investigations led to the identification of several effector substrates, particularly fatty acid binding protein-1 (FABP1) as essential for the AGR2-mediated effects. AGR2 was coexpressed with FABP1, and knockdown of AGR2 resulted in a reduction in FABP1 stability. Physical interactions of AGR2 and FABP1 depended on the PDI motif in AGR2 and the formation of a disulfide bond between these two proteins. Overexpression of AGR2 but not a mutant AGR2 protein lacking PDI activity suppressed lipid accumulation in cells lacking FABP1. Moreover, AGR2 deficiency significantly reduced fatty acid absorption in the intestine, which might be resulted from decreased fatty acid transporter CD36 in mice. These findings demonstrated a novel role of AGR2 in fatty-acid uptake and activation in both the liver and intestine, which contributed to the AGR2-mediated lipid accumulation, suggesting that AGR2 is an important regulator of whole-body lipid metabolism and down-regulation of AGR2 may antagonize the development of obesity.

The cytidine repressor regulates the survival of Pantoea agglomerans YS19 under oxidative stress and sulfur starvation conditions.

Pantoea agglomerans YS19 is a dominant endophytic bacterium isolated from rice, which is capable of promoting host plant growth by nitrogen-fixing and phytohormone secreting. We previously found that the cytidine repressor (CytR) protein conducts the regulation of indole signal in YS19. Here, we compared the whole-cell protein of the wild type YS19 and the ΔcytR mutant and subsequently identified one differential protein as alkyl hydroperoxide reductase subunit C related to oxidative stress and sulfur starvation tolerance. It was tested that cytR had a positive effect on the survival of YS19 under the oxidative stress and sulfur starvation conditions and this effect was inhibited by indole. To further understand the functional mode of indole in this regulation, we cloned the cytR promoter region (PcytR) of YS19 and tested the effect of indole on PcytR using gfp as a reporter gene. It was found that PcytR can sense indole and significantly inhibit the expression of the downstream gene. This study provided a deeper understanding of the multiple function of cytR and expanded a new research direction of how indole participates in gene regulation.