Imparting Ultrahigh Strength to Polymers via a New Concept Strategy of Construction of up to Duodecuple Hydrogen Bonding among Macromolecular Chains.

Interconnecting macromolecules via multiple hydrogen bonds (H-bonds) can simultaneously strengthen and toughen polymers, but material synthesis becomes extremely difficult with increasing number of H-bonding donors and acceptors; therefore, most reports are limited to triple and quadruple H-bonds. Herein, this bottleneck is overcome by adopting a quartet-wise approach of constructing H-bonds instead of the traditional pairwise method. Thus, large multiple hydrogen bonds can be easily established, and the supramolecular interactions are further reinforced. Especially, when such multiple H-bond motifs are embedded in polymers, four macromolecular chains-rather than two as usual-are tied, distributing the applied stress over a larger volume and more significantly improving the overall mechanical properties. Proof-of-concept studies indicate that the proposed intermolecular multiple H-bonds (up to duodecuple) are readily introduced in polyurethane. A record-high tensile strength (105.2 MPa) is achieved alongside outstanding toughness (352.1 MJ m-3), fracture energy (480.7 kJ m-2), and fatigue threshold (2978.4 J m-2). Meantime, the polyurethane has acquired excellent self-healability and recyclability. This strategy is also applicable to nonpolar polymers, such as polydimethylsiloxane, whose strength (15.3 MPa) and toughness (50.3 MJ m-3) are among the highest reported to date for silicones. This new technique has good expandability and can be used to develop even more and stronger polymers.

Dapagliflozin prevents kidney podocytes pyroptosis via miR-155-5p/HO-1/NLRP3 axis modulation.

Diabetic nephropathy (DN) is a significant clinical microvascular complication associated with diabetes mellitus (DM), and end-stage diabetes giving rise to kidney failure is developing into the major etiological factor of chronic kidney failure. Dapagliflozin is reported to limit podocyte damage in DM, which has proven to protect against renal failure. Mounting evidence has demonstrated that pyroptosis is associated with DM progression. Nevertheless, whether pyroptosis causes DN and the underlying molecular pathways remain obscure. In this study, we aimed to explore the antipyroptotic attributes of dapagliflozin and elucidate the underlying mechanisms of kidney damage in diabetes. In vivo, experiments were conducted in streptozotocin (STZ)-induced type 2 diabetic mice, which were administered dapagliflozin via gavage for 6 weeks. Subsequently, the specific organizational characteristics and expression of pyroptosis-related genes were evaluated. Intragastric dapagliflozin administration markedly reduced renal tissue injury. Meanwhile, dapagliflozin also attenuated the expression level of pyroptosis associated genes, including ASC, cleaved Caspase-1, GSDMD N-termini, NLRP3, IL-18, and IL-1ß in renal tissue of dapagliflozin-treated animals. Similar antipyroptotic effects were observed in palmitic acid (PA)-treated mouse podocytes. We also found that heme oxygenase 1 (HO-1) enhanced the protection of mouse podocyte clone 5 cells (MPC5). Moreover, miR-155-5p inhibition increased pyroptosis in PA-treated MPC5 cells, suggesting that miR-155-5p acts as an endogenous stimulator that increases HO-1 expression and reduces pyroptosis. Hence, our findings imply that dapagliflozin inhibits podocyte pyroptosis via the miR-155-5p/HO-1/NLRP3 axis in DM. Furthermore, dapagliflozin substitution may be regarded as an effective strategy for preventing pyroptosis in the kidney, including a therapeutic option for treating pyroptosis-related DN.

The management of a duodenal fistula involving the right hepatic duct: a rare case report.

The formation of an internal fistula between the biliary system and the gastrointestinal tract is a rare condition with various etiologies, predominantly associated with recurrent chronic inflammation of the biliary system and tumors. Patients with this condition may lack specific clinical manifestations, presenting with symptoms such as abdominal pain, fever, jaundice, or may show no clinical signs at all. Common types of internal fistulas include cholecystoduodenal fistula, cholecystocolonic fistula, and choledochoduodenal fistula. Among these, the right hepaticoduodenal fistula is extremely rare and seldom reported in clinical literature. We herein report a case of right hepaticoduodenal fistula and analyze its mechanism, treatment principles, and preventive measures through a literature review.

A patient with Owren disease requires pancreatic surgery: A case report.

RATIONALE: Coagulation factor V deficiency is rare, and perioperative management of patients with this condition is particularly important, especially during major abdominal surgery. We present a case of a patient with pancreatic duct stones combined with coagulation factor V deficiency. We share our perioperative management experience. PATIENT CONCERNS: A 31-year-old man presented with recurrent upper abdominal pain for 2 years. DIAGNOSES: The diagnosis of pancreatic duct stones in the patient has been established through abdominal computed tomography and magnetic resonance imaging examinations. The diagnosis of factor V deficiency was initially identified through coagulation function tests, revealing significant prolongation of both aPTT and PT. Subsequent testing of coagulation factors and inhibitors demonstrated that the patient has a deficiency in coagulation factor V. Finally, genetic testing revealed that the factor V deficiency in this case is hereditary. INTERVENTIONS: The patient underwent a partial resection of the pancreatic head, and FFP was infused 1 hour before surgery. 600 mL of FFP was instilled 1 hour before the start of surgery along with 10 U of cryoprecipitate. and 600 ml of FFP were added during surgery. Postoperative treatment included intermittent FFP supplemental infusion in the first 5 days after surgery while monitoring the coagulation function. OUTCOMES: The patient underwent a successful surgery without any abnormal bleeding or oozing during the procedure. The postoperative recovery was smooth, with no abnormal bleeding. LESSONS: Patients with a deficiency of coagulation factor V are not contraindicated for surgery. Appropriate Fresh Frozen Plasma (FFP) replacement therapy can ensure the safe conduct of the surgical procedure. For patients with abnormal blood coagulation function, we recommend testing for coagulation factors and inhibitors, as well as performing genetic testing for abnormal coagulation factors, which can provide guidance on marriage and childbirth.

Ultrastrong bonding, on-demand debonding, and easy re-bonding of non-sticking materials enabled by reversibly interlocked macromolecular networks-based Janus-like adhesive.

Simultaneously gluing hydrophobic and hydrophilic materials is a highly desired but intractable task. Herein, we developed a facile strategy using reversibly interlocked macromolecular networks (ILNs) as an adhesive. As shown by the proof-of-concept assembly of glass/ILNs/fluoropolymer (i.e., a simplified version of a photovoltaic module), the sandwiched ILNs were stratified after hot-pressing owing to temporary decrosslinking enabled by the built-in reversible covalent bonds. The fragmented component networks were enriched near their respective thermodynamically favored substrates to form a Janus-like structure. Strong elaborate interfacial bespoke chemical bonds and mechanical interlocking were thus established accompanied by the reconstruction of ILNs after cooling, which cooperated with the robust cohesion of the core part of the ILNs resulting from topological entanglements and led to a record-high peeling strength of 64.86 N cm-1. Also, the ILN-based Janus-like adhesive possessed reversible recyclability, adhesivity and on-demand de-bondability. The molecular design detailed in this study serves as a guide for developing a high-performance smart adhesive that firmly bonds non-sticking materials. Compared with existing Janus adhesives, our ILNs-based adhesive not only shows extremely useful reversibility but also greatly simplifies the adhesion process with no surface treatment required.

The OsNAC24-OsNAP protein complex activates OsGBSSI and OsSBEI expression to fine-tune starch biosynthesis in rice endosperm.

Starch accounts for up to 90% of the dry weight of rice endosperm and is a key determinant of grain quality. Although starch biosynthesis enzymes have been comprehensively studied, transcriptional regulation of starch-synthesis enzyme-coding genes (SECGs) is largely unknown. In this study, we explored the role of a NAC transcription factor, OsNAC24, in regulating starch biosynthesis in rice. OsNAC24 is highly expressed in developing endosperm. The endosperm of osnac24 mutants is normal in appearance as is starch granule morphology, while total starch content, amylose content, chain length distribution of amylopectin and the physicochemical properties of the starch are changed. In addition, the expression of several SECGs was altered in osnac24 mutant plants. OsNAC24 is a transcriptional activator that targets the promoters of six SECGs; OsGBSSI, OsSBEI, OsAGPS2, OsSSI, OsSSIIIa and OsSSIVb. Since both the mRNA and protein abundances of OsGBSSI and OsSBEI were decreased in the mutants, OsNAC24 functions to regulate starch synthesis mainly through OsGBSSI and OsSBEI. Furthermore, OsNAC24 binds to the newly identified motifs TTGACAA, AGAAGA and ACAAGA as well as the core NAC-binding motif CACG. Another NAC family member, OsNAP, interacts with OsNAC24 and coactivates target gene expression. Loss-of-function of OsNAP led to altered expression in all tested SECGs and reduced the starch content. These results demonstrate that the OsNAC24-OsNAP complex plays key roles in fine-tuning starch synthesis in rice endosperm and further suggest that manipulating the OsNAC24-OsNAP complex regulatory network could be a potential strategy for breeding rice cultivars with improved cooking and eating quality.

Sunlight Stimulated Photochemical Self-Healing Polymers Capable of Re-Bonding Damages up to a Centimeter Below the Surface Even Out of the Reach of the Illumination.

The development of photochemical self-healing polymers faces the the following bottlenecks: i) only the surface cracks can be restored and ii) materials' mechanical properties are lower. To break these bottlenecks, cross-linked poly(urethane-dithiocarbamate)s carrying photo-reversible dithiocarbamate bonds covalently linked to indole chromophores and benzyl groups are designed. The conjugated structure of the chromophore and benzyl enhances the addition reactivity of thiocarbonyl moiety and facilitates photo-cleavage of CS bond, so that transfer of the created radicals among dithiocarbamate linkages is promoted. Accordingly, reshuffling of the reversibly cross-linked networks via dynamic exchange between the activated dithiocarbamates is enabled in both surface layer and the interior upon exposure to the low-intensity ultraviolet (UV) light from the sun. It is found that the damages up to a centimeter below the surface can be effectively recovered in the sunshine, which greatly exceeds the maximum penetration distance of UV light (hundreds of microns). Besides, tensile strength and failure strain of the poly(urethane-dithiocarbamate) are superior to the reported photo-reversible polymers, achieving the record-high 33.8 MPa and 782.0% owing to the wide selectivity of soft/hard blocks, multiple interactions, and appropriate cross-linking architecture. The present work provides a novel paradigm of photo self-healing polymers capable of re-bonding cracks even out of the reach of the illumination.

Direct Hydroxylarylation of Benzylic Carbons (sp3/sp2/sp) via Radical-Radical Cross-Coupling Powered by Paired Electrolysis.

Diaryl alcohol moieties are widespread in pharmaceuticals. Existing methods for the synthesis of diaryl alcohols require the use of pre-functionalized benzylic alcohols, aromatic aldehydes, or ketones as starting materials. Herein, the first convergent paired electrochemical approach to the direct hydroxylarylation of unactivated benzylic carbons (sp3/sp2/sp) is proposed. This protocol features direct functionalization of unactivated benzylic C(sp3)-H bonds and benzylic sp2/sp-carbons, mild conditions (open air, room temperature), an environmentally friendly procedure (without any external catalyst/mediator/additive), and direct access to sterically hindered alcohols from inexpensive and readily available alkyl/alkenyl/alkynylbenzenes. Mechanistic studies, including divided-cell experiments, isotope labeling, radical trapping, electron paramagnetic resonance, reaction kinetics, and cyclic voltammetry, strongly support the proposed radical-radical cross-coupling between transient ketyl radicals and persistent radical anions. Gram-scale synthesis and diversification of drug derivatives have visualized the tremendous potential of this protocol for practical applications.

OsNAC129 Regulates Seed Development and Plant Growth and Participates in the Brassinosteroid Signaling Pathway.

Grain size and the endosperm starch content determine grain yield and quality in rice. Although these yield components have been intensively studied, their regulatory mechanisms are still largely unknown. In this study, we show that loss-of-function of OsNAC129, a member of the NAC transcription factor gene family that has its highest expression in the immature seed, greatly increased grain length, grain weight, apparent amylose content (AAC), and plant height. Overexpression of OsNAC129 had the opposite effect, significantly decreasing grain width, grain weight, AAC, and plant height. Cytological observation of the outer epidermal cells of the lemma using a scanning electron microscope (SEM) revealed that increased grain length in the osnac129 mutant was due to increased cell length compared with wild-type (WT) plants. The expression of OsPGL1 and OsPGL2, two positive grain-size regulators that control cell elongation, was consistently upregulated in osnac129 mutant plants but downregulated in OsNAC129 overexpression plants. Furthermore, we also found that several starch synthase-encoding genes, including OsGBSSI, were upregulated in the osnac129 mutant and downregulated in the overexpression plants compared with WT plants, implying a negative regulatory role for OsNAC129 both in grain size and starch biosynthesis. Additionally, we found that the expression of OsNAC129 was induced exclusively by abscisic acid (ABA) in seedlings, but OsNAC129-overexpressing plants displayed reduced sensitivity to exogenous brassinolide (BR). Therefore, the results of our study demonstrate that OsNAC129 negatively regulates seed development and plant growth, and further suggest that OsNAC129 participates in the BR signaling pathway.

Tailored modular assembly derived self-healing polythioureas with largely tunable properties covering plastics, elastomers and fibers.

To impart self-healing polymers largely adjustable dynamicity and mechanical performance, here we develop libraries of catalyst-free reversible polythioureas directly from commodity 1,4-phenylene diisothiocyanate and amines via facile click chemistry based modular assembly. By using the amine modules with various steric hindrances and flexibilities, the reversible thiourea units acquire triggering temperatures from room temperature to 120 °C. Accordingly, the derived self-healable, recyclable and controlled degradable dynamically crosslinked polythioureas can take effect within wide temperature range. Moreover, mechanical properties of the materials can be tuned covering plastics, elastomers and fibers using (i) different assemble modules or (ii) solid-state stretching. Particularly, unidirectional stretching leads to the record-high tensile strength of 266 MPa, while bidirectional stretching provides the materials with biaxial strengths up to over 120 MPa. The molecular mechanism and technological innovations discussed in this work may benefit promotion and application of self-healing polymers towards greatly diverse demands and scenarios.

Amplification of the Fluorescence Signal with Clustered Regularly Interspaced Short Palindromic Repeats-Cas12a Based on Au Nanoparticle-DNAzyme Probe and On-Site Detection of Pb2+ Via the Photonic Crystal Chip.

Although great headway has been made in DNAzyme-based detection of Pb2+, its adaptability, sensitivity, and accessibility in complex media still need to be improved. For this, we introduce new ways to surmount these hurdles. First, a spherical nucleic acid (SNA) fluorescence probe (Au nanoparticles-DNAzyme probe) is utilized to specifically identify Pb2+ and its suitability for precise detection of Pb2+ in complex samples due to its excellent nuclease resistance. Second, the sensitivity of Pb2+ detection is greatly enhanced via the use of a clustered regularly interspaced short palindromic repeats-Cas12a with target recognition accuracy to amplify the fluorescent signal upon the trans cleavage of the SNA (signal probe), and the limit of detection reaches as low as 86 fM. Third, we boost the fluorescence on photonic crystal chips with a bionic periodic arrangement by employing a straightforward detection device (smartphone and portable UV lamp) to achieve on-site detection of Pb2+ with the limit of detection as low as 24 pM. Based on the abovementioned efforts, the modified Pb2+ fluorescence sensor has the advantages of higher sensitivity, better specificity, accessibility, less sample consumption, and so forth. Moreover, it can be applied to accurately detect Pb2+ in complex biological or environmental samples, which is of great promise for widespread applications.

High-resolution quantitative trait locus mapping for rice grain quality traits using genotyping by sequencing.

Rice is a major food crop that sustains approximately half of the world population. Recent worldwide improvements in the standard of living have increased the demand for high-quality rice. Accurate identification of quantitative trait loci (QTLs) for rice grain quality traits will facilitate rice quality breeding and improvement. In the present study, we performed high-resolution QTL mapping for rice grain quality traits using a genotyping-by-sequencing approach. An F2 population derived from a cross between an elite japonica variety, Koshihikari, and an indica variety, Nona Bokra, was used to construct a high-density genetic map. A total of 3,830 single nucleotide polymorphism markers were mapped to 12 linkage groups spanning a total length of 2,456.4 cM, with an average genetic distance of 0.82 cM. Seven grain quality traits-the percentage of whole grain, percentage of head rice, percentage of area of head rice, transparency, percentage of chalky rice, percentage of chalkiness area, and degree of chalkiness-of the F2 population were investigated. In total, 15 QTLs with logarithm of the odds (LOD) scores >4 were identified, which mapped to chromosomes 6, 7, and 9. These loci include four QTLs for transparency, four for percentage of chalky rice, four for percentage of chalkiness area, and three for degree of chalkiness, accounting for 0.01%-61.64% of the total phenotypic variation. Of these QTLs, only one overlapped with previously reported QTLs, and the others were novel. By comparing the major QTL regions in the rice genome, several key candidate genes reported to play crucial roles in grain quality traits were identified. These findings will expedite the fine mapping of these QTLs and QTL pyramiding, which will facilitate the genetic improvement of rice grain quality.

Clinical factors influencing the effect of anti-reflux surgery for gastroesophageal reflux disease / 中华普通外科杂志

Objective:to analyze the risk factors for the side effect of anti-reflux surgery for gastroesophageal reflux disease (GERD) with regards to relief of reflux symptom, dysphagia and postoperative satisfaction.Method:The incidence of disappointing chief complaint among 192 patients who underwent anti-reflux surgery was analyzed. The related independent risk factors were identified by multivariate analysis.Results:The incidence of non-relief of reflux symptom was approximately 21.8% (42 cases), of which the risk factors were identified as preoperative depression and long-term PPI administration. The incidence of persistent dysphagia was 7.3% (14 cases), of which the risk factors were identified as preoperative depression and weak peristalsis of esophageal body. The incidence of postoperative dissatisfaction was 26.0% (50 cases), of which the risk factors were identified as long-term PPI administration and moderate-severe depression. The GERD patients with hiatal hernia and low pressure of lower esophageal sphincter were more likely benefit from anti-reflux surgery and had a higher postoperative satisfaction rate.Conclusion:Hiatal hernia and low pressure of lower esophageal sphincter are the favorable factors predicting good result of anti-reflux surgery. Long-term PPI administration and preoperative depression is an indication for poor result of anti-reflux surgery.

Biomimetic Chip Enhanced Time-Gated Luminescent CRISPR-Cas12a Biosensors under Functional DNA Regulation.

Despite that the currently discovered CRISPR-Cas12a system is beneficial for improving the detection accuracy and design flexibility of luminescent biosensors, there are still challenges to extend target species and strengthen adaptability in complicated biological media. To conquer these obstacles, we present here some useful strategies. For the former, the limitation to nucleic acids assay is broken through by introducing a simple functional DNA regulation pathway to activate the unique trans-cleavage effect of this CRISPR system, under which the expected biosensors are capable of effectively transducing a protein (employing dual aptamers) and a metal ion (employing DNAzyme). For the latter, a time-gated luminescence resonance energy transfer imaging manner using a long-persistent nanophosphor as the energy donor is performed to completely eliminate the background interference and a nature-inspired biomimetic periodic chip constructed by photonic crystals is further combined to enhance the persistent luminescence. In line with the above efforts, the improved CRISPR-Cas12a luminescent biosensor not only exhibits a sound analysis performance toward the model targets (carcinoembryonic antigen and Na+) but also owns a strong anti-interference feature to actualize accurate sensing in human plasma samples, offering a new and applicative analytical tool for laboratory medicine.

Preparation of a water soluble aminated ß-1,3-D-glucan for gene carrier: The in vitro study of the anti-inflammatory activity and transfection efficiency.

ß-1,3-D-glucan has been reported to have a series of bioactivities including antitumor, antimicrobial, anti-inflammatory and antioxidative effects; however, its insolubility in neutral aqueous solution significantly restricts the potential application in biological and medicine fields. Herein, a water-soluble aminated ß-1,3-D-glucan (AG) was synthesized and the anti-inflammatory effect, cytotoxicity and plasmid DNA (pDNA) binding capacity of AG, serum stability, the particle sizes and zeta potentials of AG/pDNA nanocomposites, and the transfection efficiency and mechanism of action were studied. AG shows no obvious cytotoxicity within the range of working concentration (1-64 µg/ml) and it exerts potent anti-inflammatory effect independent on Dectin-1 and TLR2. AG/pDNA nanocomposites prepared by electrostatic interaction possess an appropriate particle size ranged from 192.8 to 118.4 nm and zeta potentials ranged from 20.880 to 27.16 mV with the N/P ratios from 5 to 100. AG/pDNA nanocomposites at the N/P ratios of 10 and 20 were able to show superior transfection efficiencies in RAW 264.7 cells as a result of their suitable particle size, zeta potential, anti-inflammatory effect, and the specific interaction with pattern recognition receptors (Dectin-1 and TLR2). These results indicate that AG is a potential candidate for DNA delivery system due to its potent anti-inflammatory effect and high transfection efficiency.

Dynamically Cross-Linked Polymeric Binder-Made Durable Silicon Anode of a Wide Operating Temperature Li-Ion Battery.

The colossal volumetric expansion (up to 300%) of the silicon (Si) anode during repeated charge-discharge cycles destabilizes the electrode structure and causes a drastic drop in capacity. Here in this work, commercial poly(acrylic acid) (PAA) is cross-linked by hydroxypropyl polyrotaxane (HPR) via reversible boronic ester bonds to achieve a water-soluble polymeric binder (PAA-B-HPR) for making the Si anode of the Li-ion battery. Slidable α-cyclodextrins of modified polyrotaxane are allowed to move around when the unwanted volume variation occurs in the course of lithiation and delithiation so that the accumulated internal stress can be equalized throughout the system, while the reversible boronic ester bonds are capable of healing the damages created during manufacturing and service to maintain the electrode integrity. As a result, the Li-ion battery assembled with the Si anode comprised of the PAA-B-HPR binder possesses outstanding specific capacity and cycle stability within a wide temperature range from 25 to 55 °C. Especially, the Si@PAA-B-HPR anode exhibits a discharge specific capacity of 1056 mA h/g at 1.4 A/g after 500 cycles under a higher temperature of 55 °C, and the corresponding capacity fading rate per cycle is only 0.10%. The present work opens an avenue toward the practical application of the Si anode for Li-ion batteries.

Polymorphism, expression and structure analysis of key genes in the ovarian steroidogenesis pathway in sheep (Ovis aries).

BACKGROUND: Litter size is an important factor that significantly affects the development of the sheep industry. Our previous TMT proteomics analysis found that three key proteins in the ovarian steroidogenesis pathway, STAR, HSD3B1, and CYP11A1, may affect the litter size trait of Small Tail Han sheep. OBJECTIVE: The purpose of this study was to better understand the relationship between polymorphisms of these three genes and litter size. MATERIAL AND METHOD: Sequenom MassARRAY detected genetic variance of the three genes in 768 sheep. Real-time qPCR of the three genes was used to compare their expression in monotocous and polytocous sheep in relevant tissues. Finally, bioinformatics analysis predicted the protein sequences of the different SNP variants. RESULT: Association analysis showed that there was a significant difference in litter size among the genotypes at two loci of the CYP11A1 gene (p < 0.05), but no significant difference was observed in litter size among all genotypes at all loci of the STAR and HSD3B1 genes (p > 0.05). However, STAR expression was significantly different in polytocous and monotocous sheep in the pituitary (p < 0.01). Tissue-specific expression in the ovary was observed for HSD3B1 (p < 0.05), but its expression was not different between polytocous and monotocous sheep. Bioinformatics analysis showed that the g.33217408C > T mutation of CYP11A1 resulted in major changes to the secondary and tertiary structures. In contrast, gene polymorphisms in STAR and HSD3B1 had minimal impacts on their protein structures. DISCUSSION: This may explain why the CYP11A1 variant impacted litter size while the others did not. The single nucleotide polymorphism of the CYP11A1 gene would serve as a good molecular marker when breeding to increase litter size in sheep. Our study provides a basis for further revealing the function of the ovarian steroidogenesis pathway in sheep reproduction and sheep breeding.

Radix Kansui Stir-Fried with Vinegar Reduces Radix Kansui-Related Hepatotoxicity in Mice via Mitochondrial Pathway.

OBJECTIVE: To investigate the mechanism of Radix Kansui (RK) stir-fried with vinegar (VRK) decreased hepatotoxicity in mice. METHODS: According to a random number table, 40 mice were randomly divided into negative control group (0.5% carboxymethylcellulose sodium, 20 mL/kg), positive control group (0.1% mixture of carbon tetrachloride in soybean oil, 20 mL/kg), RK group (the ethyl acetate extracts of RK, 250 g crude drug/kg) and VRK group (the ethyl acetate extracts of VRK, 250 g crude drug/kg) with 10 mice per group. All mice were administered orally by gavage daily for 7 continuous days. The morphology of liver tissues was examined to assess the liver injury by a transmission electron microscope. Hepatocyte apoptosis in vivo was determined by terminal deoxynucleotidyltransferase-mediated dUTP-biotin nickend labeling (TUNEL) assay. Immunohistochemical technique was adopted to detect the expression of particular antiapoptotic and proapoptotic proteins in the mitochondrial pathways, including B-cell lymphoma (Bcl-2) and caspase-3, as well as the expression of inflammatory mediators, including nuclear factor kappa B (NF- κ B) and intercellular adhesion molecule-1 (ICAM-1). RESULTS: Liver injury and hepatocyte apoptosis were observed in RK mice, and the liver injury were significantly reduced in VRK-treated mice. In immunohistochemistry study, compared with the negative control group, RK inhibited dramatically the Bcl-2 protein expression and significantly increased the expression of caspase-3, NF- κ B and ICAM-1 (all P<0.01). Compared with the RK group, VRK group induced significant increase on Bcl-2 protein expression, and decreased the caspase-3, NF- κ B and ICAM-1 protein expression (P<0.05 or P<0.01). CONCLUSION: The mechanism of reduced hepatotoxicity of VRK may be associated with the reduced inflammation, regulation of antiapoptotic and proapoptotic mediators in the mitochondrial pathway.

Radix Kansui Stir-Fried with Vinegar Reduces Radix Kansui-Related Hepatotoxicity in Mice via Mitochondrial Pathway / 中国结合医学杂志

OBJECTIVE@#To investigate the mechanism of Radix Kansui (RK) stir-fried with vinegar (VRK) decreased hepatotoxicity in mice.@*METHODS@#According to a random number table, 40 mice were randomly divided into negative control group (0.5% carboxymethylcellulose sodium, 20 mL/kg), positive control group (0.1% mixture of carbon tetrachloride in soybean oil, 20 mL/kg), RK group (the ethyl acetate extracts of RK, 250 g crude drug/kg) and VRK group (the ethyl acetate extracts of VRK, 250 g crude drug/kg) with 10 mice per group. All mice were administered orally by gavage daily for 7 continuous days. The morphology of liver tissues was examined to assess the liver injury by a transmission electron microscope. Hepatocyte apoptosis in vivo was determined by terminal deoxynucleotidyltransferase-mediated dUTP-biotin nickend labeling (TUNEL) assay. Immunohistochemical technique was adopted to detect the expression of particular antiapoptotic and proapoptotic proteins in the mitochondrial pathways, including B-cell lymphoma (Bcl-2) and caspase-3, as well as the expression of inflammatory mediators, including nuclear factor kappa B (NF- κ B) and intercellular adhesion molecule-1 (ICAM-1).@*RESULTS@#Liver injury and hepatocyte apoptosis were observed in RK mice, and the liver injury were significantly reduced in VRK-treated mice. In immunohistochemistry study, compared with the negative control group, RK inhibited dramatically the Bcl-2 protein expression and significantly increased the expression of caspase-3, NF- κ B and ICAM-1 (all P<0.01). Compared with the RK group, VRK group induced significant increase on Bcl-2 protein expression, and decreased the caspase-3, NF- κ B and ICAM-1 protein expression (P<0.05 or P<0.01).@*CONCLUSION@#The mechanism of reduced hepatotoxicity of VRK may be associated with the reduced inflammation, regulation of antiapoptotic and proapoptotic mediators in the mitochondrial pathway.