Silencing of LAMC2 Reverses Epithelial Mesenchymal Transition and Inhibits Progression in Pancreatic Ductal Adenocarcinoma via Inactivation of the NF-κB Signaling Pathway.

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most difficult to treat of all malignancies. Multimodality regimens provide only short-term symptomatic improvement with minor impact on survival, underscoring the urgent need for novel therapeutics and treatment strategies for PDAC. We screened out the highly expressed gene LAMC2 in PDAC tissues through the GEO online database, and further demonstrated that it is related to the poor prognosis of PDAC patients. Next, we investigated the effect of LAMC2 in the development and metastasis of PDAC by silencing LAMC2 expression in PDAC cells. The results showed that silencing of LAMC2 inhibited the proliferation, invasion and metastasis, and promoted apoptosis of PDAC cells, silencing of LAMC2 also reversed the epithelial mesenchymal transition (EMT) and suppressed the activation of NF-κB signaling pathway. Our results identify LAMC2 as a pivotal regulator of PDAC malignant progression, and its overexpression is sufficient to confer the characteristically aggressive clinical features of this disease.

Blockade of Indoleamine 2,3-Dioxygenase attenuates lipopolysaccharide-induced kidney injury by inhibiting TLR4/NF-κB signaling.

Blockade of indoleamine 2,3-dioxygenase (IDO) has been shown to alleviate lipopolysaccharide (LPS)-induced endotoxic shock and reduce sepsis mortality, but its effect on LPS-induced kidney damage has not been reported. Herein, we established a mouse kidney injury model by intraperitoneal injection of 10 mg/kg LPS and established an in vitro renal tubular epithelial cell injury model by stimulating TCMK-1 cells with 10 mg/L LPS. We found that pretreatment with 1-methyl tryptophan (1-MT), an IDO inhibitor, significantly improved LPS-induced mouse survival, and IDO knockout (KO) mice also had higher survival rates after LPS exposure than wild-type mice. At the same time, IDO KO or pretreatment with 1-MT not only reduced serum creatinine, blood urea nitrogen, renal tubular injury pathological score, but also inflammatory factors and oxidative stress status in serum or kidney of LPS-exposed mice. In vitro, blockade of IDO with 1-MT significantly inhibited LPS-induced apoptosis, inflammation and oxidative stress in TCMK-1 cells. In addition, blockade of IDO significantly inhibited LPS-activated TLR4/NF-κB signaling pathway in kidney of mice or in TCMK-1 cells. In conclusion, our results suggested that blockade of IDO attenuated kidney inflammation, apoptosis and oxidative stress to protect against LPS-induced septic kidney injury via inhibiting the TLR4/NF-κB signaling pathway.

A noval prognostic signature of the N7-methylguanosine (m7G)-related miRNA in lung adenocarcinoma.

BACKGROUND: Lung adenocarcinoma (LUAD) is characterized by high morbidity and mortality rates and poor prognosis. N7-methylguanosine play an increasingly vital role in lung adenocarcinoma. However, the prognostic value of N7-methylguanosine related-miRNAs in lung adenocarcinoma remains unclear. METHODS: In the study, the mRNA and miRNA expression profiles and corresponding clinical informations were downloaded from the public database. The prognostic signature was built using least absolute shrinkage and selection operator Cox analysis. The Kaplan-Meier method was used to compare survival outcomes between the high- and low-risk groups. Signatures for the development of lung adenocarcinoma were tested using univariate and multivariate Cox regression models. Single-sample gene set enrichment analysis was used to determine the immune cell infiltration score. First, we predicted METTL1 and WDR4 chemosensitivities based on a public pharmacogenomics database. The area under the receiver operating characteristic curve showed that the performance of signature in 1-,3-, and 5-year survival predictions were 0.68, 0.65, and 0.683, respectively. RESULTS: We established a novel prognostic signature consisting of 9 N7-Methylguanosine related miRNAs using least absolute shrinkage and selection operator Cox analysis. Patients in the high-risk group had shorter survival times than those in the low-risk group did. The calibration curves at 1, 3, and 5-year also illustrate the high predictive power of the structure. Signature was corrected using the Toumor stage. The expression levels of METTL1 and WDR4 significantly correlated with the sensitivity of cancer cells to antitumor drugs. CONCLUSIONS: A novel signature constructed using 9 N7-methylguanosine related-miRNAs can be used for prognostic prediction.

MiR-302b-5p enhances the neuroprotective effect of IGF-1 in methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinson's disease by regulating inducible nitric-oxide synthase.

Parkinson's disease (PD) is a neurodegenerative disease which results in damage in neuronal cells. Insulin-like growth factor (IGF)-1 was previously reported to play a role of neuroprotection in some diseases. Nitric oxide (NO) can also regulate neuronal cells. However, the mechanisms underlying IGF-1 and NO in PD still need to be elucidated. In present study, we explored the interaction between IGF-1 and inducible Nitric-Oxide Synthase (iNOS) in PD progression. We firstly constructed PD models by methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or MPP+ treatment. Then RT-qPCR revealed that IGF-1 expression was downregulated while iNOS expression was upregulated in MPTP model. Moreover, IGF-1 elevation or iNOS depletion enhanced cell viability and blocked cell apoptosis. Rescue assay disclosed iNOS overexpression reversed the effect on viability and apoptosis mediated by IGF-1 upregulation. Furthermore, IGF-1 was identified to positively regulate miR-302b-5p which could target iNOS. MiR-302b-5p could abolish the inhibitory function IGF-1 exerted on cell apoptosis and iNOS could counteract miR-302b-5p upregulation-triggered inhibition on cell apoptosis as well. Besides, we observed the deficiency of miR-302b-5p improved the lesioned neurobehavior of MPTP-treated mice. To sum up, present study proved that miR-302b-5p enhanced the neuroprotective effect of IGF-1 in MPTP-induced PD by regulating iNOS, recommending a novel therapeutic target for PD treatment. SIGNIFICANCE OF THE STUDY: In this study, we mainly explored that IGF-1 was decreased while iNOS was boosted in MPTP-induced PD mice model; IGF-1 suppressed while iNOS promoted MPP+ -induced toxicity and apoptosis in SH-SY5Y cells; miR-302b-5p ehanhced the neuroprotective effect of IGF-1 via targeting Inos; deficiency of miR-302b-5p improved the lesioned neurobehavior of MPTP-treated mice.

[Case-control study of the relationship between dietary fatty acids intake and non-alcoholic fatty liver disease in Nanping City, 2015-2017].

OBJECTIVE: To explore the relationship between different kinds of dietary fatty acids intake and non-alcoholic fatty liver disease(NAFLD). METHODS: A 1↿ frequency matched case-control study was conducted among 546 NAFLD patients diagnosed by ultrasound as case group, 546 people without NAFLD randomly selected and matched by sex and age(±5) as control group from April 2015 to August 2017 in Nanping first hospital. The data was obtained from participants using structured questionnaires during face-to-face interviews. Information on dietary intake was collected using semi-quantitative food frequency questionnaires. Residual method was used to derive energy-adjusted variable, unconditional Logistic regression was used to estimate odds ratios(OR) and their 95% CI. RESULTS: The NAFLD group consumed a significantly higher amount of fatty acid(FAs), saturated fatty acid(SFAs), mono-unsaturatedfattyacids(MUFAs), poly-unsaturated fatty acids(PUFAs), n-3 PUFAs, n-6 PUFAs, C16↿, C18↿, C16↿, C18↿, C18↿ and C18↿. Multivariate unconditional Logistic regression analysis indicated that daily intake of total fatty acids, MUFAs, n-6 PUFAs, C18↿, C18↿ more than 98. 96 g/d, 38. 83 g/d, 26. 23 g/d, 33. 55 g/d and 24. 91 g/d respectively, were the risk factors for NAFLD. The adjusted ORs and 95% CI were 2. 26(1. 49-3. 44), 1. 93(1. 29-2. 88), 5. 13(3. 40-7. 76), 1. 82(1. 22-2. 79) and 5. 24(3. 40-7. 76). Daily intake of C20↿, C22↿ in 0. 07-0. 09 g/d, 0. 01-0. 02 g/d were the protective factors for NAFLD. The adjusted ORs and 95% CI were 0. 58(0. 39-0. 85) and 0. 64(0. 43-0. 94). CONCLUSION: Daily intake of total fatty acids, MUFAs, n-6 PUFAs, C18↿, C18↿ more than 98. 96, 38. 83, 26. 23, 33. 55 and 24. 91 g/d respectively, were the risk factors for NAFLD. Daily intake of C20↿, C22↿ in 0. 07-0. 09 g/d, 0. 01-0. 02 g/d respectively, were the protective factors for NAFLD.

Highly Conductive Polysiloxane Elastomers with Excellent Transparency, Resilience, and Stretchability.

Flexible transparent conductive materials show great potential in wearable electronics, flexible sensors, and so on. But the most used flexible conductive materials like hydrogels and ionogels suffer from evaporation and solvent leakage. For the application in these fields, integrated performances of preeminent resilience, transparency, stability, and conductivity that do not change with deformation are prerequisites. It is still challenging to handle the trade-off among these performances. Herein, a facile approach is established to balance these properties into one elastomer. Through the thiol-ene click reaction, mercaptopropyl-modified polydimethylsiloxane (mPDMS) is cross-linked and grafted by PEG-based macromonomers to prepare conductive elastomers. By anchoring with mPDMS through carbon-sulfur bonds, PEG can be evenly dispersed, resulting in ultratransparency (97%) and stable conductivity of as high as 1.68 × 10-2 S m-1, comparable to pure PEG/lithium salt conductivity. It also has a wide electrochemical stability window with a high voltage of 4.8 V. Moreover, the multibond network strategy is employed through grafting ligand 1-vinylimidazole to mPDMS to construct dynamic cross-links between Zn(II) and 1-vinylimidazol, bestowing excellent properties to the elastomers. Overall, elastomers with a well-balanced performance of high resilience, good conductivity, and ultratransparency are obtained, providing promising applications for soft electronics, lithium battery electrolytes, and flexible devices.

Carthamin yellow attenuates brain injury in a neonatal rat model of ischemic-hypoxic encephalopathy by inhibiting neuronal ferroptosis in the hippocampus.

Hypoxic-ischemic encephalopathy (HIE) is a common neurological disorder characterized by ischemia and hypoxia in the perinatal period, which seriously affects the growth and development of newborns. To date, there is no specific drug for the treatment of HIE. Previous studies have shown that ferroptosis plays an important role in the pathogenesis of HIE. Carthamin yellow (CY) is believed to have antioxidant and anti-inflammatory effects. However, no studies have reported the role of CY in ferroptosis in HIE in vivo until now. The aim of this study was to investigate the effect and mechanism of CY on HIE in vivo and to provide an experimental basis for the clinical treatment of HIE. The results demonstrated that CY increased the expression of NeuN in the neonatal rat hypoxic-ischemic brain damage (HIBD) model. Further exploration revealed that CY increased the expression of glutathione peroxidase 4 and ferritin heavy chain 1 while it decreased the expression of PTGS2 and ACSL2. Moreover, CY decreased malondialdehyde expression and increased superoxide dismutase and glutathione expression in vivo. The findings also indicated that CY downregulated the expression of Nrf2 and Keap-1. In conclusion, this study demonstrated that CY attenuated brain injury in an experimental HIBD model, potentially by alleviating hippocampal neuronal ferroptosis through inhibition of the Nrf2/Keap-1 signaling pathway. These findings provide a novel therapeutic strategy for the clinical treatment of HIE.

Saffron reduces the liver fibrosis in mice by inhibiting the JAK/STAT3 pathway.

PURPOSE: Chronic inflammation in the liver is a key trigger for liver injury and fibrosis in various liver diseases. Given the anti-inflammatory and antioxidant effects of Saffron, this study aimed to investigate the pharmacological effects of Saffron on hepatic inflammation and fibrosis. METHODS: The mice model of hepatic fibrosis was constructed using CCl4, and Saffron was administered at low (10 mg/kg) and high (20 mg/kg) doses by gavage. Then, the changes in liver function, liver inflammation and fibrosis markers were evaluated. The effects and mechanisms of Saffron on hepatic stellate cells were further investigated in in-vitro experiments. RESULTS: Saffron improved liver function, reduced liver inflammation and attenuated liver fibrosis in a dose-dependent manner in hepatic fibrosis mice. Furthermore, Western blotting showed that Saffron significantly inhibited JAK/STAT3 phosphorylation in fibrotic livers. CONCLUSIONS: Saffron can attenuate liver fibrosis by inhibiting the JAK/STAT3 pathway and the activation of hepatic stellate cell, providing a theoretical basis for the development of new anti-fibrotic drugs.

Characterization of the biological and transcriptomic signatures of natural killer cells derived from cord blood and peripheral blood.

Longitudinal studies have indicated the pivotal role of natural killer cells (NKs) in the elimination of certain infections and malignancies. Currently, perinatal blood (PB) and cord blood (CB) have been considered with promising prospective for autogenous and allogeneic NKs transplantation, yet the similarities and differences at the biological and molecular levels are largely obscure. We isolated mononuclear cells (MNCs) from PB and CB, and compared the biological phenotypes of resident NKs by flow cytometry and cell counting. Then, we turned to our well-established "3ILs" strategy and co-culture for NK cell activation and cytotoxicity analyses, respectively. Finally, with the aid of transcriptomic analyses, we further dissected the signatures of PB-NKs and CB-NKs. CB-NKs revealed superiority in cellular vitality over PB-NKs, together with variations in subpopulations. CB-NKs showed higher cytotoxicity over PB-NKs against K562 cells. Furthermore, we found both NKs revealed multifaceted conservations and differences in gene expression profiling and genetic variations, together with gene subsets and signaling pathway. Collectively, both NKs revealed multifaceted similarities and diverse variations at the cellular and transcriptomic levels. Our findings would benefit the further exploration of the biological and transcriptomic properties of CB-NKs and PB-NKs, together with the development of NK cell-based cytotherapy.

CAR-NK cells for acute myeloid leukemia immunotherapy: past, present and future.

Acute myeloid leukemia (AML) is a deadly disease and the most common leukemia in adult with clonal heterogeneity and abnormity in myeloid lineages, which has been recognized with high morbidity and mortality attributes to the recurrence and resistance to chemotherapy. Numerous literatures have indicated the encouraging progress in allogeneic hematopoietic stem cell transplantation (allo-HSCT) and chimeric antigen receptor-transduced T (CAR-T) cells. However, the outcomes of recurrent and refractory AML (r/rAML) patients with current strategies are still unsatisfactory, which largely due to the matching restriction as well as adverse reactions, including graft-versus-host disease (GvHD), neurotoxicity and cytokine release syndrome (CRS). State-of-the-art literatures have indicated CAR-transduced NK (CAR-NK) cells for the management of diverse hematologic malignancies including AML, which are recognized as novel weapons for reinforcing the specificity and cytotoxicity of autogenous and allogeneic "off-the-shelf" NK cells dispense with prior sensitization. Therefore, in this review, we mainly focus on the latest updates of alternative cell sources, therapeutic targets, CAR-modification and delivery strategies, standardization and productization, together with prospective and challenges of CAR-NK cell-based cytotherapy, which will collectively benefit the further development of novel treatment paradigms for combating AML via both CAR-dependent and NK cell receptor-dependent signaling cascades in future.

The Influence of SiO2 + SiC + Al (H2PO4)3 Coating on Mechanical and Dielectric Properties for SiCf/MWCNTS/AlPO4 Composites.

SiC fiber-reinforcedAlPO4 matrix (SiCf/MWCNTs/AlPO4) composites were fabricated using a hot laminating process with multi-walled carbon nanotubes (MWCNTs) as the absorber. A coating prepared from SiO2 + SiC + Al (H2PO4)3 was applied to the surface of the SiCf/MWCNTs/AlPO4 composites prior to an anti-oxidation test at 1273 K in air for 40 h. The anti-oxidation effect was verified by a three-point bending test, scanning electron microscopy, transmission electron microscopy, X-ray diffraction, and a dielectric property test. Anti-oxidation mechanism investigations revealed that the coating effectiveness could be attributed to three substances, i.e., SiO2, SiP2O7, and SiO2 +AlPO4 solid solution from the reactions of SiC + O2→SiO2 + CO, SiO2 + P2O5→SiP2O7 and SiO2 +AlPO4→solid solution, respectively.

Super Tough and Intelligent Multibond Network Physical Hydrogels Facilitated by Ti3C2Tx MXene Nanosheets.

Stretchable and conductive hydrogels have emerged as promising candidates for intelligent and flexible electronic devices. Herein, based on a multibond network (MBN) design rationale, super tough and highly stretchable nanocomposite physical hydrogels are prepared, where 2D Ti3C2Tx MXene nanosheets serve as multifunctional cross-linkers and effective stress transfer centers. Further MXene-poly(acrylic acid) (PAA)-Fe3+ MBN physical hydrogels fabricated through controlled permeation of Fe3+ exhibit prominent and well-balanced mechanical properties (e.g., the tensile strength can reach 10.4 MPa and elongation at break can be as high as 3080%), attributed to the dual cross-linking network with dense Fe3+-mediated coordination cross-links between MXene nanosheets and PAA chains and sparse carboxy-Fe3+ cross-links between PAA chains. Moreover, both conductive MXene nanosheets and numerous ions endow the hydrogels with superior conductivity (up to 3.8 S m-1), strain sensitivity (high gauge factor of 10.09), and self-healing performance, showing great prospect as intelligent flexible electronics.

Silencing of long non-coding RNA ZFAS1 alleviates LPS-induced acute lung injury by mediating the miR-96-5p/OXSR1 axis in sepsis.

BACKGROUND: Extensive studies have revealed that long non-coding RNAs (lncRNAs) are associated with sepsis-induced acute lung injury (ALI). This study focused on the function and potential mechanisms of lncRNA zinc finger antisense 1 (ZFAS1) in a cell model of sepsis-induced ALI. METHODS: To induce sepsis-induced ALI in vitro and in vivo, mice were subjected to cecal ligation and puncture (CLP) operation, and human small airway epithelial cells (HSAECs) were stimulated with lipopolysaccharide (LPS) (10 µg/mL). Relative expression of oxidative stress-responsive 1 (OXSR1), lncRNA ZFAS1, and microRNA (miR)-96-5p was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Relative protein expression of Bax, Bcl-2, and OXSR1 was determined by western blotting. Moreover, enzyme-linked immunosorbent assay was used to measure the levels of IL-6, IL-1ß, and TNF-α. A dual-luciferase reporter assay was conducted to test the targeting interplay between ZFAS1/OXSR1 and miR-96-5p. RESULTS: Up-regulation of lncRNA ZFAS1 and OXSR1 and down-regulation of miR-96-5p was observed in lung tissues of CLP-induced mice and LPS-treated HSAECs. Decreased ZFAS1 expression or increased miR-96-5p expression repressed inflammation and apoptosis and promoted cell viability in LPS-treated HSAECs. The lncRNA ZFAS1 competitively binds to miR-96-5p and inversely modulates miR-96-5p expression. MiR-96-5p directly targets OXSR1 and inversely regulates OXSR1 expression. In addition, the protective effects of ZFAS1 knockdown on LPS-induced HSAECs were reversed by miR-96-5p inhibition or OXSR1 overexpression. CONCLUSIONS: Down-regulation of lncRNA ZFAS1 attenuated LPS-induced ALI in HSAECs by regulating the miR-96-5p/OXSR1 axis.

Isoliquiritigenin attenuates neuroinflammation in mice model of Parkinson's disease by promoting Nrf2/NQO-1 pathway.

Parkinson's disease (PD) is a common neurodegenerative disease that severely affects the quality of life of patients. There is no specific drug for PD up to now. Previous studies have shown that neuroinflammation plays an important role in the pathogenesis of PD. Isoliquiritigenin (ILG) is thought to have a variety of biological activities including anti-inflammatory. However, to date, no studies have reported the role of ILG on neuroinflammation in PD in vivo. This study aimed to investigate the effect of ILG on PD in vivo and its mechanism, and to provide an experimental basis for clinical treatment of PD. Our results showed that ILG at a concentration of 20 mg/kg was effective in reducing the number of rotations in PD mice. In addition, ILG increased the expression of tyrosine hydroxylase and decreased the expression of α-synuclein. The results also showed that ILG reduced the expression of Iba1, IL-1ß, IL-6, and TNF-α. Not only that, ILG also upregulated the expression of Nrf2 and NQO-1 in vivo. Our results suggest that ILG significantly attenuates neurological deficits in PD, and the mechanism may be through the activation of the Nrf2/NQO-1 signaling pathway to reduce neuroinflammation. Moreover, our findings provide a new therapeutic strategy for PD.

Biomimetic Gradient Hydrogel Actuators with Ultrafast Thermo-Responsiveness and High Strength.

Most current hydrogel actuators suffer from either poor mechanical properties or limited responsiveness. Also, the widely used thermo-responsive poly-(N-isopropylacrylamide) (PNIPAM) homopolymer hydrogels have a slow response rate. Thus, it remains a challenge to fabricate thermo-responsive hydrogel actuators with both excellent mechanical and responsive properties. Herein, ultrafast thermo-responsive VSNPs-P(NIPAM-co-AA) hydrogels containing multivalent vinyl functionalized silica nanoparticles (VSNPs) are fabricated. The ultrafast thermo-responsiveness is due to the mobile polymer chains grafted from the surfaces of the VSNPs, which can facilitate hydrophobic aggregation, inducing the phase transition and generating water transport channels for quick water expulsion. In addition, the copolymerization of NIPAM with acrylic acid (AA) decreases the transition temperature of the thermo-responsive PNIPAM-based hydrogels, contributing to ultrafast thermo-responsive shrinking behavior with a large volume change of as high as 72.5%. Moreover, inspired by nature, intelligent hydrogel actuators with gradient structure can be facilely prepared through self-healing between the ultrafast thermo-responsive VSNPs-P(NIPAM-co-AA) hydrogel layers and high-strength VSNPs-PAA-Fe3+ multibond network (MBN) hydrogel layers. The obtained well-integrated gradient hydrogel actuators show ultrafast thermo-responsive performance within only 9 s in 60 °C water, as well as high strength, and can be used for more practical applications as intelligent soft actuators or artificial robots.

Correlation between 1-FABP, Blood Routine and Grading of Necrotising Enterocolitis.

Correlation was sought between serum intestinal fatty acid binding protein (I-FABP), blood routine examination indexes, and necrotizing enterocolitis (NEC) disease classification. According to Bell-NEC grade, 86 children with NEC were divided into mild group (46 cases) and severe group (40 cases). Serum I-FBAP and blood routine indices including white blood cells (WBC), platelets (PLT), neutrophils and lymphocytes were determined. Serum levels of I-FABP and WBC in severe group were higher than those in mild group (both p <0.001), and serum level of PLT was lower than that in mild group (p <0.001). NEC grade was positively correlated with I-FABP and WBC (r=0. 930, p <0.001; r=0. 946, p <0.001), negatively correlated with PLT (r=-0. 602, p <0.001), and had weak correlation with neutrophils and lymphocytes (r=0. 186, p=0. 087; r=0. 072, p=0. 509). In conclusion, serum levels of I-FABP, WBC and PLT were correlated with the severity of NEC in children, which could be used as a reference index to judge prognosis of NEC children. Key Words: Necrotizing enterocolitis of newborn (NEC), Serum, Intestinal fatty acid binding protein (I-FABP), Routine blood indices.

Association between nut intake and non-alcoholic fatty liver disease risk: a retrospective case-control study in a sample of Chinese Han adults.

OBJECTIVES: Nut consumption has been associated with a lower risk of type 2 diabetes, metabolic syndrome and insulin resistance. However, its effect on the risk of non-alcoholic fatty liver disease (NAFLD) is unknown. Therefore, we investigated the relationship between nut consumption and NAFLD risk. SETTING AND PARTICIPANTS: We conducted a retrospective case-control study including 534 patients diagnosed with NAFLD and 534 controls matched by sex and age (±5 years) from the Affiliated Nanping First Hospital of Fujian Medical University in China. MAIN OUTCOME MEASURES: Information on dietary intake was collected using a semiquantitative food frequency questionnaire and nut consumption was calculated. Nut consumption was categorised using quartiles based on the distribution of daily nut intake of the controls. Binary logistic regression models were used to estimate ORs and the 95% CIs for the association between nut consumption and NAFLD risk. RESULTS: After adjusting for potential confounding variables, nut consumption was not associated with NAFLD risk in the overall sample. When the fully adjusted model was stratified by sex, a significant inverse association was found between high nut consumption and NAFLD only among the men in the highest quartile (OR=0.43; 95% CI 0.26 to 0.71; Ptrend = 0.01). The inverse association of nut consumption with NAFLD risk in men remained significant after controlling for other known or suspected risk factors for NAFLD. CONCLUSIONS: Diets with a higher intake of nuts may be associated with a decreased risk of NAFLD, particularly in men.

[Novel synthesis and spectral characterization of nelfinavir].

An efficient and environmentally friendly procedure for the one-pot synthesis of (3S,4aS,8aS)-2-((2R,3R)-3-amino-2-hydroxy-4-(phenylthio)butyl)- N-tert -butyl-decahydroisoquinoline-3-carboxamide(VII), the intermediate of nelfinavir, was described, and activating ester was applied to getting nelfinavir(IX). Under the catalysis of potassium hydroxide, benzyl (R)-1-((S)-oxiran-yl)-2-(phenylthio) ethyl carbamate was obtained(IV) in methanol. Then IV and (3S,4aS,8aS)- N-tert -butyl-decahydroisoquinoline-3-carboxamide(V) were refluxed in methanol until the reaction was finished. Potassium hydroxide(w(KOH) = 40%) in water was added to remove benzyloxycarbonyl group in water bath with a yield of 89.0%. 3-acetoxy-2-methylbenzoic acid-succinimide ester(II) reacted with VII and acetyl group was removed by dense aqueous ammonia, giving nelfinavir(IX). The vibrations of functional groups of thiIIs compound corresponding to the main infrared absorption peaks were discussed. The molecular ion and quasi molecular ion peaks were obtained via MALDI-TOF MS, and 1H NMR and 13CNMR shifts of this compound were assigned by means of DEPT(distortionless enhancement by polarization transfer spectrum), HMBC(1H detected heteronuclearmultiple bond correlation spectrum), HSQC(1H detected heteronuclear single-quantum coherence spectrum) and DQF-COSY(double-quantum filtered-correlated spectroscopy). The results provided useful information for structure characterization and quality control of nelfinavir.

Omega-3 polyunsaturated fatty acid supplementation and non-alcoholic fatty liver disease: A meta-analysis of randomized controlled trials.

BACKGROUND: Clinical trials examining the therapeutic benefit of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) on nonalcoholic fatty liver disease (NAFLD) have reported inconsistent results. We performed a meta-analysis of randomized controlled trials (RCTs) examining the effect of ω-3 PUFA supplementation on NAFLD, and provide substantial evidence on whether ω-3 PUFA supplementation has a favorable effect for treating NAFLD. METHODS: We searched the PubMed, Cochrane Library, Springer Link, China National Knowledge Infrastructure (CNKI), Wanfang, and Chinese Scientific and Technological Journal (VIP) databases for RCTs on oral ω-3 PUFA supplementation in patients with NAFLD. The data were pooled; meta-analyses were conducted using random-effect or fixed-effect models. RESULTS: Eighteen studies involving 1424 patients were included. We found a significant benefit for ω-3 PUFAs vs control for liver fat, alanine aminotransferase, aspartate aminotransferase, γ-glutamyl transferase, triglycerides, insulin resistance, and glucose. However, there was significant interstudy heterogeneity. Subgroup and regression analyses showed no significantly clear methodologic discrepancy. Publication bias and serious adverse events were not detected. CONCLUSIONS: Our meta-analysis suggests that ω-3 PUFA supplementation may decrease liver fat and hepatic enzyme parameters. However, more large-scale, well-designed RCTs are needed to confirm the effect of ω-3 PUFA supplementation on these parameters.

Saffron reduces the liver fibrosis in mice by inhibiting the JAK/STAT3 pathway

Purpose: Chronic inflammation in the liver is a key trigger for liver injury and fibrosis in various liver diseases. Given the anti-inflammatory and antioxidant effects of Saffron, this study aimed to investigate the pharmacological effects of Saffron on hepatic inflammation and fibrosis. Methods: The mice model of hepatic fibrosis was constructed using CCl4, and Saffron was administered at low (10 mg/kg) and high (20 mg/kg) doses by gavage. Then, the changes in liver function, liver inflammation and fibrosis markers were evaluated. The effects and mechanisms of Saffron on hepatic stellate cells were further investigated in in-vitro experiments. Results: Saffron improved liver function, reduced liver inflammation and attenuated liver fibrosis in a dose-dependent manner in hepatic fibrosis mice. Furthermore, Western blotting showed that Saffron significantly inhibited JAK/STAT3 phosphorylation in fibrotic livers. Conclusions: Saffron can attenuate liver fibrosis by inhibiting the JAK/STAT3 pathway and the activation of hepatic stellate cell, providing a theoretical basis for the development of new anti-fibrotic drugs.