AP39, a novel mitochondria-targeted hydrogen sulfide donor ameliorates doxorubicin-induced cardiotoxicity by regulating the AMPK/UCP2 pathway.

Doxorubicin (DOX) is a broad-spectrum, highly effective antitumor agent; however, its cardiotoxicity has greatly limited its use. Hydrogen sulfide (H2S) is an endogenous gaseous transmitter that exerts cardioprotective effects via the regulation of oxidative stress and apoptosis and maintenance of mitochondrial function, among other mechanisms. AP39 is a novel mitochondria-targeted H2S donor that, at appropriate concentrations, attenuates intracellular oxidative stress damage, maintains mitochondrial function, and ameliorates cardiomyocyte injury. In this study, DOX-induced cardiotoxicity models were established using H9c2 cells and Sprague-Dawley rats to evaluate the protective effect of AP39 and its mechanisms of action. Both in vivo and in vitro experiments showed that DOX induces oxidative stress injury, apoptosis, and mitochondrial damage in cardiomyocytes and decreases the expression of p-AMPK/AMPK and UCP2. All DOX-induced changes were attenuated by AP39 treatment. Furthermore, the protective effect of AP39 was significantly attenuated by the inhibition of AMPK and UCP2. The results suggest that AP39 ameliorates DOX-induced cardiotoxicity by regulating the expression of AMPK/UCP2.

Chelation-directed interface engineering of in-place self-cleaning membranes.

Water-energy sustainability will depend upon the rapid development of advanced pressure-driven separation membranes. Although energy-efficient, water-treatment membranes are constrained by ubiquitous fouling, which may be alleviated by engineering self-cleaning membrane interfaces. In this study, a metal-polyphenol network was designed to direct the armorization of catalytic nanofilms (ca. 18 nm) on inert polymeric membranes. The chelation-directed mineralized coating exhibits high polarity, superhydrophilicity, and ultralow adhesion to crude oil, enabling cyclable crude oil-in-water emulsion separation. The in-place flux recovery rate exceeded 99.9%, alleviating the need for traditional ex situ cleaning. The chelation-directed nanoarmored membrane exhibited 48-fold and 6.8-fold figures of merit for in-place self-cleaning regeneration compared to the control membrane and simple hydraulic cleaning, respectively. Precursor interaction mechanisms were identified by density functional theory calculations. Chelation-directed armorization offers promise for sustainable applications in catalysis, biomedicine, environmental remediation, and beyond.

Metabolomics analysis delineates the therapeutic effects of Yinlan Tiaozhi capsule on triton WR-1339 -induced hyperlipidemia in mice.

Hyperlipidemia is a disorder of lipid metabolism resulting from abnormal blood lipid metabolism and is one of the most frequent metabolic diseases that endanger people's health. Yinlan Tiaozhi capsule (YL) is a formulated TCM widely used to treat hyperlipidemia. The purpose of this study was to discover biomarkers utilizing untargeted metabolomics techniques, as well as to analyze the mechanisms underlying the changes in metabolic pathways linked to lipid-lowering, anti-inflammation, and regulation of angiogenesis in hyperlipidemia mice. To assess the efficacy of YL, serum total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c) levels were measured. Biochemical examinations showed that YL significantly reduced the levels of TC, TG, LDL-c, Il6, Tnf-α, and Vegfa in hyperlipidemia mice (p < 0.01). YL also significantly increased the levels of HDL-c and Alb (p < 0.01). Twenty-seven potential serum biomarkers associated with hyperlipidemia were determined. These differential metabolites were related to the reduction of serum lipid levels in hyperlipidemia mice, probably through metabolic pathways such as linoleic acid metabolism, glycerophospholipid metabolism, phenylalanine metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, and D-glutamine and D-glutamate metabolism. Further correlation analysis showed that the serum lipid reduction through YL was related to the metabolites (amino acid metabolites, phospholipids metabolites, and fatty acids metabolites). The present study reveals that YL has a profound effect on alleviating triton WR-1339-induced hyperlipidemia, inflammation, and angiogenesis and that the positive effects of YL were primarily associated with the correction of metabolic abnormalities and the maintenance of metabolite dynamic balance.

[Prediction and analysis of Q-markers of Elephantopus scaber based on its UPLC fingerprint, content determination of components, and in vitro a nti-tumor activity].

This study aimed to provide scientific evidence for predicting quality markers(Q-markers) of Elephantopus scaber by establishing UPLC fingerprint of E. scaber from different geographical origins and determining the content of 13 major components, as well as conducting in vitro anti-cancer activity investigation of the main components. The chromatographic column used was Waters CORTECS UPLC C_(18)(2.1 mm×150 mm, 1.6 µm), and the mobile phase consisted of acetonitrile and 0.1% formic acid solution(gradient elution). The column temperature was set at 30 ℃, and the flow rate was 0.2 mL·min~(-1). The injection volume was 1 µL, and the detection wavelength was 240 nm. The UPLC fingerprint of E. scaber was fitted using the Similarity Evaluation System for Chromatographic Fingerprint of Traditional Chinese Medicine(2012 edition) to determine common peaks, evaluate similarity, identify and determine the content of major components. The CCK-8 assay was used to explore the inhibitory effect of the main components on the proliferation of lung cancer cells. The results showed that in the established UPLC fingerprint of E. scaber, 35 common peaks were identified. Thirteen major components, including neochlorogenic acid(peak 1), chlorogenic acid(peak 2), cryptochlorogenic acid(peak 3), caffeic acid(peak 4), schaftoside(peak 6), galuteolin(peak 9), isochlorogenic acid B(peak 10), isochlorogenic acid A(peak 12), isochlorogenic acid C(peak 18), deoxyelephantopin(peak 28), isodeoxyelephantopin(peak 29), isoscabertopin(peak 31), and scabertopin(peak 32) were identified and quantified, and a quantitative analysis method was established. The results of the in vitro anti-cancer activity study showed that deoxyelephantopin, isodeoxyelephantopin, isoscabertopin, and scabertopin in E. scaber exhibited inhibition rates of lung cancer cell proliferation exceeding 80% at a concentration of 10 µmol·L~(-1), higher than the positive drug paclitaxel. These results indicate that the fingerprint of E. scaber is highly characteristic, and the quantitative analysis method is accurate and stable, providing references for the research on quality standards of E. scaber. Four sesquiterpene lactones in E. scaber show significant anti-cancer activity and can serve as Q-markers for E. scaber.

Engineering In Situ Catalytic Cleaning Membrane Via Prebiotic-Chemistry-Inspired Mineralization.

Pressure-driven membrane separation promises a sustainable energy-water nexus but is hindered by ubiquitous fouling. Natural systems evolved from prebiotic chemistry offer a glimpse of creative solutions. Herein, a prebiotic-chemistry-inspired aminomalononitrile (AMN)/Mn2+ -mediated mineralization method is reported for universally engineering a superhydrophilic hierarchical MnO2 nanocoating to endow hydrophobic polymeric membranes with exceptional catalytic cleaning ability. Green hydrogen peroxide catalytically triggered in-situ cleaning of the mineralized membrane and enabled operando flux recovery to reach 99.8%. The mineralized membrane exhibited a 9-fold higher recovery compared to the unmineralized membrane, which is attributed to active catalytic antifouling coupled with passive hydration antifouling. Electron density differences derived from the precursor interaction during mediated mineralization unveiled an electron-rich bell-like structure with an inner electron-deficient Mn core. This work paves the way to construct multifunctional engineered materials for energy-efficient water treatment as well as for diverse promising applications in catalysis, solar steam generation, biomedicine, and beyond.

Low-carbohydrate diet in the treatment of type 2 diabetes mellitus (LoCaT): study protocol for a multicenter, randomized controlled trial.

BACKGROUND: Low-carbohydrate diet (LCD) is an emerging therapy for type 2 diabetes mellitus (T2DM). Although its effect on glucose control has been confirmed in previous clinical trials, most of those studies have focused on comparing calorie-restricted LCD to iso-caloric low-fat diets. In this study, we aim to compare the effects of LCD and canagliflozin, a sodium-glucose cotransporter 2 inhibitor, in patients with T2DM. METHODS: This is a multicenter, randomized controlled trial. We will recruit 120 patients with poor-controlled T2DM. Participants will be randomly divided into canagliflozin and LCD groups in a 1:1 ratio. The primary outcome is the change in hemoglobin A1C levels after the 3-month intervention. The secondary outcomes are the time in range and cost of antihyperglycemic agents. Exploratory outcomes include physical examination, body composition, glucose variability, appetite, glycolipid metabolism, liver lipid content, and urine glucose threshold. DISCUSSION: No previous study has compared an LCD with antihyperglycemic agents. In LoCaT, participants' metabolism will be assessed from multiple perspectives. It is believed that the finding obtained from this trial will optimize the treatments for patients with T2DM. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1900027592. Registered on November 20, 2019.

Comprehensive insight into adsorption of chlortetracycline hydrochloride by room-temperature synthesized water-stable Zr-based metal-organic gel/sodium alginate beads.

Chlortetracycline hydrochloride (CTC) is one of the prevailing antibiotic pollutants that harm both environmental ecosystem and human health. Herein, Zr-based metal-organic gels (Zr-MOGs) with lower-coordinated active sites and hierarchically porous structures are fabricated via a facile straightforward room-temperature strategy for CTC treatment. More importantly, we incorporated the powder Zr-MOGs into low-cost sodium alginate (SA) matrix to achieve shaped Zr-based metal-organic gel/SA beads for enhancing the adsorption ability and ameliorating the recyclability. The Langmuir maximum adsorption capacities of Zr-MOGs and Zr-MOG/SA beads could reach 143.9 mg/g and 246.9 mg/g, respectively. What's more, in the manual syringe unit and continuous bead column experiments, Zr-MOG/SA beads could achieve an eluted CTC removal ratio as high as 96.3% and 95.5% in the river water sample, respectively. On top of that, the adsorption mechanisms were put forward as a combination of pore filling, electrostatic interaction, hydrophilic-lipophilic balance, coordination, π-π interaction as well as hydrogen bonding interaction. This study outlines a workable strategy for the facile preparation of candidate adsorbents for wastewater treatment.

Deciphering the mechanisms of Yinlan Tiaozhi capsule in treating hyperlipidemia by combining network pharmacology, molecular docking and experimental verification.

Yinlan Tiaozhi capsule (YLTZC) has been widely used to treat hyperlipidemia (HLP). However, its material basis and underlying pharmacological effects remain unclean. The current study aimed to explore the mechanisms involved in the treatment of YLTZC on HLP based on network pharmacology, molecular docking, and experimental verification. Firstly, UPLC-Q-TOF-MS/MS was used to comprehensively analyze and identify the chemical constituents in YLTZC. A total of 66 compounds, mainly including flavonoids, saponins, coumarins, lactones, organic acids, and limonin were characterized and classified. Simultaneously, the mass fragmentation pattern of different types of representative compounds was further explored. By network pharmacology analysis, naringenin and ferulic acid may be the core constituents. The 52 potential targets of YLTZC, including ALB, IL-6, TNF, and VEGFA, were considered potential therapeutic targets. Molecular docking results showed that the core active constituents of YLTZC (naringenin and ferulic acid) have a strong affinity with the core targets of HLP. Lastly, animal experiments confirmed that naringenin and ferulic acid significantly upregulated the mRNA expression of ALB and downregulated the mRNA expression of IL-6, TNF, and VEGFA. In sum, the constituents of YLTZC, such as naringenin and ferulic acid, might treat HLP by regulating the mechanism of angiogenesis and inhibiting inflammatory responses. Furthermore, our data fills the gap in the material basis of YLTZC.

The history and mystery of sacubitril/valsartan: From clinical trial to the real world.

Heart failure is a serious threat to human health, with morbidity and mortality rates increasing despite the existence of multiple treatment options. Therefore, it is necessary to identify new therapeutic targets for this disease. Sacubitril/valsartan is a supramolecular sodium salt complex of the enkephalinase inhibitor prodrug sacubitril and the angiotensin receptor blocker valsartan. Its combined action increases endogenous natriuretic peptides while inhibiting the renin-angiotensin-aldosterone system and exerting cardioprotective effects. Clinical evidence suggests that sacubitril/valsartan is superior to conventional renin-angiotensin-aldosterone inhibitor therapy for patients with reduced ejection fraction heart failure who can tolerate angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers. The therapy reduces the risk of heart failure hospitalization, cardiovascular mortality, and all-cause mortality and has a better safety and tolerability record. This review describes the potential pathophysiological mechanisms of cardiomyocyte injury amelioration by sacubitril/valsartan. We explore the protective effects of sacubitril/valsartan and outline the therapeutic value in patients with heart failure by summarizing the results of recent large clinical trials. Furthermore, a preliminary outlook shows that sacubitril/valsartan may be effective at treating other diseases, and provides some exploratory observations that lay the foundation for future studies on this drug.

Herbal formula Jiawei Xiaochengqi decoction prevents postoperative abdominal adhesion in a rat model through inhibition of CXCL2-CXCR2 pathway.

BACKGROUND: Postoperative abdominal adhesion (PAA) is the most common complication after abdominal surgeries, which can lead to intestinal obstruction, chronic abdominal pain or female infertility. Jiawei Xiaochengqi decoction (JWXCQ) is a hospital preparation widely used for PAA treatment in Nanfang Hospital of Southern Medical University for more than twenty years. PURPOSE: This study aimed to investigate the therapeutic effects and potential mechanism of JWXCQ against PAA and provide beneficial information for its clinical application. METHODS: The main active components of JWXCQ were identified using ultra high performance liquid chromatography (UHPLC) combined with standard substance comparison. The efficacy and underlying mechanism of JWXCQ were evaluated through in vivo experiments with a postsurgical-induced peritoneal adhesion rat model, and in vitro studies with LPS-stimulated Raw 264.7 macrophages and primary fibroblasts. H&E and Masson staining were performed to assess histopathological changes. The levels of cytokines/proteins-associated with inflammation and degradation of extracellular matrix as well as CXCL2-CXCR2 pathway-related proteins were determined by ELISA, qRT-PCR, western blot assays or immunohistochemistry, respectively. Furthermore, siCXCR2 transfection was used to validate the mechanism of action of JWXCQ. RESULTS: JWXCQ treatment significantly reduced the formation of PAA, inhibited the inflammation and collagen deposition, and facilitated the secretion of MMP9, decreased the levels of IL-1ß, IL-6, TIMP1, COL-1, and suppressed the CXCL2-CXCR2 pathway in PAA rats. Furthermore, JWXCQ inhibited its downstream pathways, the JAK2-STAT3 and PI3K-AKT signaling, as indicated by the suppression of the phosphorylation levels of STAT3 and AKT. In vitro cell experiments revealed that JWXCQ reduced IL-1ß and IL-6 secretion in Raw 264.7 macrophages and COL-1 in primary fibroblasts. The CXCL2-CXCR2, JAK2-STAT3 and PI3K-AKT pathways were also inhibited after JWXCQ treatment, which were consistent with the in vivo results. More importantly, silence of CXCR2 eliminated the regulatory effects of JWXCQ. CONCLUSION: JWXCQ could effectively prevent the PAA formation by alleviating inflammation and collagen deposition, which was associated with the inhibition of CXCL2-CXCR2 pathway. This study investigated the relevant pharmacological mechanisms of JWXCQ, providing further evidence for the application of JWXCQ in clinical PAA treatment.

New insight into enhanced transport of multi-component porous covalent-organic polymers with alkyl chains as injection agents for levofloxacin removal in saturated sand columns.

Levofloxacin (LEV) is prone to be retained in aquifers due to its strong adsorption affinity onto sand, thus posing a threat to groundwater quality. In-situ injection technology for remediating LEV-contaminated soil and groundwater is still challenging owing to the lack of appropriate remedial agents. Herein, two novel multi-component porous covalent-organic polymers (namely, SLEL-1 and SLEL-2) with alkyl chains were constructed through Schiff-base reactions to adsorb LEV from an aqueous solution, in which the kinetics, isotherms, influenced factors were investigated. Plausible adsorption mechanisms were proposed through characterization and experimental analysis, including pore filling effect, π-π electron-donor-acceptor (EDA) interaction, hydrogen bonding force, hydrophobic-hydrophobic interaction as well as electrostatic force. In addition, response surface methodology (RSM) revealed the treatment optimization and reciprocal relationship within multi-variables. Furthermore, taking advantage of favorable dispersion and outstanding competitive behavior, SLEL-1 was established as an in-situ adsorptive agent in dynamic saturated columns on a laboratory scale to investigate the removal of LEV from water-bearing stratum. Overall, the findings of this work provided an insight into the fabrication of SLELs as long-term mobile and reusable adsorptive agents for practical in-situ applications in the future.

Network pharmacology analysis and experimental validation to explore the mechanism of Bushao Tiaozhi capsule (BSTZC) on hyperlipidemia.

Bushao Tiaozhi Capsule (BSTZC) is a novel drug in China that is used in clinical practice and has significant therapeutic effects on hyperlipidemia (HLP). In our previous study, BSTZC has a good regulatory effect on lipid metabolism of HLP rats. However, its bioactive compounds, potential targets, and underlying mechanism remain largely unclear. We extracted the active ingredients and targets in BSTZC from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and literature mining. Subsequently, core ingredients, potential targets, and signaling pathways were determined through bioinformatics analysis, including constructed Drug-Ingredient-Gene symbols-Disease (D-I-G-D), protein-protein interaction (PPI), the Gene Ontology (GO), and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Finally, the reliability of the core targets was evaluated using in vivo studies. A total of 36 bioactive ingredients and 209 gene targets were identified in BSTZC. The network analysis revealed that quercetin, kaempferol, wogonin, isorhamnetin, baicalein and luteolin may be the core ingredients. The 26 core targets of BSTZC, including IL-6, TNF, VEGFA, and CASP3, were considered potential therapeutic targets. Furthermore, GO and KEGG analyses indicated that the treatment of HLP by BSTZC might be related to lipopolysaccharide, oxidative stress, inflammatory response and cell proliferation, differentiation and apoptosis. The pathway analysis showed enrichment for different pathways like MAPK signaling pathway, AGE-RAGE signaling pathway in diabetic, IL-17 signaling pathway and TNF signaling pathway. In this study, network pharmacology analysis, and experiment verification were combined, and revealed that BSTZC may regulate key inflammatory markers and apoptosis for ameliorating HLP.

Three porous shapeable three-component hydrogen-bonded covalent-organic aerogels as backfill materials in a simulated permeable reactive barrier (PRB) for trapping levofloxacin.

Levofloxacin (LEV) infiltrated in groundwater has threatened the safety of drinking water. For in-situ remediation of LEV-contaminated groundwater, there exists a main challenge of exploiting proper high efficient backfill medium in utilizing charming permeable reactive barriers (PRBs). Herein, three porous shapeable three-component hydrogen-bonded covalent organic aerogels (HCOA-1, HCOA-2 and HCOA-3) were fabricated based on a multiple-linking-site strategy to evaluate for adsorptive removal of LEV. The three HCOAs exhibited satisfactory performance in LEV adsorption that could integrate high adsorption capacity, good antiion interference, excellent recyclability and wide pH tolerance. The different regularity of kinetics and isotherms of three HCOAs signified that electrostatic effect, pore preservation, hydrogen bonding probably govern the adsorption process in combination, coupling with π-π electron-donor-acceptor (EDA), dipole-dipole and hydrophobic-hydrophobic interaction besides. In addition, the response surface methodology (RSM) was employed for studying the single and synergetic effects of selected variables and optimizing operation conditions. Furthermore, a laboratory PRB column packed with processable HCOA-2 was set up to investigate the LEV removal, and the breakthrough data was explained by Adams-Bohart, Thomas, BDST and Yoon-Nelson models. We believe could hopefully bring HCOAs into the real in-situ remediation of such challenging and persistent LEV-polluted groundwater with further massive-scale efficiently.

miR-190-5p Alleviates Myocardial Ischemia-Reperfusion Injury by Targeting PHLPP1.

OBJECTIVE: Myocardial ischemia-reperfusion (I/R) injury (MIRI) refers to the more serious myocardial injury after blood flow recovery, which seriously affects the prognosis of patients with ischemic cardiomyopathy. This study explored the new targets for MIRI treatment by investigating the effects of miR-190-5p and its downstream target on the structure and function of myocardial cells. METHODS: We injected agomir miR-190-5p into the tail vein of rats to increase the expression of miR-190-5p in rat myocardial cells and made an I/R rat model by coronary artery occlusion. We used 2,3,5-triphenyl tetrazolium chloride staining, lactate dehydrogenase (LDH) detection, echocardiography, and hematoxylin-eosin (HE) staining to determine the degree of myocardial injury in I/R rats. In addition, we detected the expression of inflammatory factors and apoptosis-related molecules in rat serum and myocardial tissue to determine the level of inflammation and apoptosis in rat myocardium. Finally, we determined the downstream target of miR-190-5p by Targetscan system and dual luciferase reporter assay. RESULTS: The expression of miR-190-5p in an I/R rat myocardium was significantly lower than that in normal rats. After treatment of I/R rats with agomir miR-190-5p, the ischemic area of rat myocardium and the concentration of LDH decreased. The results of echocardiography and HE staining also found that overexpression of miR-190-5p improved the structure and function of rat myocardium. miR-190-5p was also found to improve the viability of H9c2 cells in vitro and reduce the level of apoptosis of H9c2 cells. The results of Targetscan system and dual luciferase reporter assay found that miR-190-5p targeted to inhibit pleckstrin homology domain leucine-rich repeat protein phosphatase 1 (PHLPP1). In addition, inhibition of PHLPP1 was found to improve the viability of H9c2 cells. CONCLUSION: Therefore, miR-190-5p can reduce the inflammation and apoptosis of myocardium by targeting PHLPP1, thereby alleviating MIRI.

Network Pharmacology and Molecular Docking-Based Prediction of the Mechanism of Qianghuo Shengshi Decoction against Rheumatoid Arthritis.

Qianghuo Shengshi decoction (QHSSD) is a classical Chinese medicine formula, which is used in clinical practice for the treatment of rheumatoid arthritis (RA) in China. However, the pharmacological mechanism of QHSSD on RA has remained unclear by now. We collected and screened active compounds and its potential targets by the pharmacology platform of Chinese herbal medicines. In addition, the therapeutic targets of RA were obtained and selected from databases. Network construction analyzed that 128 active compounds may act on 87 candidate targets and identified a total of 18 hub targets. GO annotation and KEGG enrichment investigated that the action mechanism underlying the treatment of RA by QHSSD might be involved in cell proliferation, angiogenesis, anti-inflammation, and antioxidation. Finally, molecular docking verification showed that TP53, VEGFA, TNF, EGFR, and NOS3 may be related to the RA treatment and molecular dynamics simulation showed the stability of protein-ligand interactions. In this work, QHSSD might exert therapeutic effect through a multicomponent, multitarget, and multipathway in RA from a holistic aspect, which provides basis for its mechanism of action and subsequent experiments.

Luminescent cellulose-based porous binary metal-organic gels in an adsorption bed for effective adsorption and sensitive detection of chlortetracycline hydrochloride.

Three novel (Fe-Eu) JLUE-MOGs were successfully fabricated through a solvothermal method and employed to construct the double-effect system for antibiotics adsorption and detection. The characterizations highlighted the properties of ample active sites, large surface areas and hierarchical porous structures, which did contribute to superb and rapid chlortetracycline hydrochloride (CTC) adsorption by JLUE-MOGs. Besides, the effects of initial pH values, JLUE-MOG dosages and co-existing inorganic ions on the CTC adsorption could be explained by pore filling, π-π EDA interaction, electrostatic interaction, water affinity as well as hydrogen bonding. Moreover, the optimized condition was cross-explored by response surface methodology (RSM) with tiny differences compared to actual experiments. In addition, fluorescent JLUE-MOG-7 was implemented for sensitive recognition of CTC and reflecting adsorption processes. Furthermore, shaping JLUE-MOG-7@cellulose aerogels were fabricated as filter materials for applying into an adsorption bed. The breakthrough process was fitted well by Bohart-Adams model and Thomas model, along with recognizable fluorescence changes of immobilized adsorbents. This work develops efficient and luminescent powder-like JLUE-MOGs for antibiotics adsorptive enrichment and sensitive detection. More importantly, immobilized JLUE-MOG@cellulose aerogels, as promising and alternative adsorbents with real-time fluorescence changes, can be utilized for continuously pollutants removal in real wastewater treatment.

Yinning Tablet, a hospitalized preparation of Chinese herbal formula for hyperthyroidism, ameliorates thyroid hormone-induced liver injury in rats: Regulation of mitochondria-mediated apoptotic signals.

ETHNOPHARMACOLOGICAL RELEVANCE: Hyperthyroidism is closely associated with liver injury. The preliminary clinical observation suggests that Yinning Tablet, a hospitalized preparation of traditional Chinese formula for hyperthyroidism, improves not only hyperthyroidism, but also hyperthyroidism-associated liver injury. AIM: To evaluate the effect and underlying mechanisms of Yinning Tablet on thyroid hormone-induced liver injury. MATERIALS AND METHODS: Female rats were orally administered L-thyroxine (1 mg/kg) once daily for 60 days, and co-treated with the carefully identified Yinning Tablet extract (0.6-2.4 g/kg) during the last 30 days. Blood and liver variables were determined enzymatically, histologically, by ELISA, radioimmunoassay, Real-Time PCR or Western blot, respectively. RESULTS: Co-treatment with the extract attenuated L-thyroxine-induced increases in serum alanine transaminase and aspartate transaminase activities, the ratio of liver weight to body weight, cytoplasmic vacuolization in hepatocytes, infiltrated inflammatory cells and confused structures in liver tissue, accompanied by attenuation of increased serum triiodo-l-thyronine concentration and hepatic deiodinase type I overexpression in rats. Importantly, Yinning Tablet suppressed L-thyroxine-triggered hepatic Bax, cleaved caspases-3, -8 and -9 protein overexpression, and Bcl-2 protein downregulation. Furthermore, the increases in cytochrome c protein expression, Ca2+-ATPase activity and malondialdehyde content, and decreases in activities of Na+/K+-ATPase, catalase, superoxide dismutase and glutathione peroxidase, and total antioxidant capacity in liver tissue were attenuated. CONCLUSION: The present results suggest that Yinning Tablet ameliorates thyroid hormone-induced liver injury in rats by regulating mitochondria-mediated apoptotic signals. Our findings go insight into the pharmacological basis of the hospitalized preparation for treatment of hyperthyroidism-associated liver injury.

Long noncoding RNA/circular noncoding RNA-miRNA-mRNA axes in cardiovascular diseases.

Cardiovascular diseases (CVDs) are the leading cause of death worldwide. Non-coding RNAs including long non-coding RNAs (lncRNAs), circular RNAs (circRNAs) and microRNAs (miRNAs) have been reported to participate in pathological developments of CVDs through various mechanisms. Among them, the networks among lncRNAs/circRNAs, miRNAs, and mRNAs have recently attracted attention. Understanding the molecular mechanism could aid the discovery of therapeutic targets or strategies in CVDs including atherosclerosis, myocardial infarction (MI), hypertrophy, heart failure (HF) and cardiomyopathy. In this review, we summarize the latest research involving the lncRNA/circRNA-miRNA-mRNA axis in CVDs, with emphasis on the molecular mechanism.

Chronic treatment with the modified Longdan Xiegan Tang attenuates olanzapine-induced fatty liver in rats by regulating hepatic de novo lipogenesis and fatty acid beta-oxidation-associated gene expression mediated by SREBP-1c, PPAR-alpha and AMPK-alpha.

ETHNOPHARMACOLOGICAL RELEVANCE: The modified Longdan Xiegan Tang (mLXT) has been used clinically for various neuropsychiatric disorders and liver diseases. The use of antipsychotics is associated with nonalcoholic fatty liver disease. AIM OF THE STUDY: To investigate the effect and underlying mechanisms of mLXT on antipsychotic-induced fatty liver. MATERIALS AND METHODS: The representative active components in the formula were identified and quantified by a HPLC method. Fatty liver in male rats was induced by olanzapine (5 mg/kg) (p.o., × 8 weeks), and the rats were co-treated with mLXT extract (50 and 500 mg/kg). Blood and liver variables were determined enzymatically or histologically. Gene/protein expression was analyzed by real-time PCR and Western blot. RESULTS: Treatment of rats with mLXT decreased olanzapine-induced increases in hepatic triglyceride content, cell vacuolar degeneration and Oil Red O-stained area, accompanied by suppression of olanzapine-stimulated hepatic mRNA and/or protein overexpression of sterol regulatory element-binding protein (SREBP)-1c, and its downstream lipogenic enzymes for de novo lipogenesis. Besides, mLXT also activated hepatic expression of peroxisome proliferator-activated receptor-alpha and its target genes associated with fatty acid beta-oxidation, phosphorylated Thr172 in AMP-activated protein kinase (AMPK)-alpha (the upstream enzyme of SREBP-1c and PPAR-alpha), and its ratio to total AMPK-alpha. CONCLUSIONS: The present results suggest that chronic treatment with mLXT ameliorates olanzapine-induced fatty liver by regulating hepatic de novo lipogenesis- and fatty acid beta-oxidation-associated gene expression mediated by SREBP-1c and PPAR-alpha, respectively, through activation of AMPK-alpha. Our findings provide the evidence that supports clinical use of the formula for antipsychotic medication-induced fatty liver.