[Retracted] Tripartite motif­containing 14 regulates cell proliferation and apoptosis in cervical cancer via the Akt signaling pathway.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that the GAPDH control western blotting data shown in Fig. 2B were strikingly similar to data appearing in different form in Fig. 1E in another article written by different authors at different research institutes [Liang T, Ye X, Liu Y, Qiu X, Li Z, Tian B and Yan D: FAM46B inhibits cell proliferation and cell cycle progression in prostate cancer through ubiquitination of ß­catenin. Exp Mol Med 50: 1­12, 2018]. Owing to the fact that the contentious data in the above article had already been published prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 22: 5145­5154, 2020; DOI: 10.3892/mmr.2020.11634].

Chinese Herbal Extracts Mitigate Ammonia Generation in the Cecum of Laying Hens: An In Vitro Study.

The objectives of the study were to screen one or several Chinese herbal extracts with good ammonia emission reduction effects using an in vitro gas production study. The study consisted of a control (without Chinese herbal extract), and 11 experimental groups with added cinnamon extract (CE), Osmanthus extract (OE), tangerine peel extract (TPE), dandelion extract (DE), Coptis chinensis extract (CCE), honeysuckle extract (HE), Pulsatilla root extract (PRE), yucca extract (YE), licorice extract (LE), Ginkgo biloba extract (GBE), or astragalus extract (AE). The results showed that HE, PRE, YE, LE, GBE, and AE significantly reduced ammonia production (p ≤ 0.05). The most significant ammonia inhibition was achieved via AE, resulting in a 26.76% reduction. In all treatments, Chinese herbal extracts had no significant effect on pH, conductivity, or uric acid, urea, and nitrate-nitrogen concentrations (p > 0.05). However, AE significantly reduced urease activity and the relative activity of uricase (p ≤ 0.05). AE significantly increased the relative abundance of Bacteroides and decreased the relative abundance of Clostridium, Desulfovibrio, and Prevotell (p ≤ 0.05). Astragalus extract inhibited ammonia emission from laying hens by changing the gut microbial community structure, reducing the relative abundance of ammonia-producing bacteria, and reducing microorganisms' uricase and urease activities.

Estimating canopy stomatal conductance and photosynthesis in apple trees by upscaling parameters from the leaf scale to the canopy scale in Jinzhong Basin on Loess Plateau.

The estimations of stomatal conductance and photosynthesis performed by upscaling the parameters from the leaf scale to the canopy scale are key points in the fields of forest ecohydrology and physiology. The foundation for solving this scientific problem is determining the optimal models for calculating the leaf stomatal conductance (gl) and photosynthetic rate (Pl). In this study, we used the Jarvis model combined with modification factors, including leaf-air temperature (ΔT) and CO2 concentration inside and outside the stomata (ΔC), to estimate gl and the new Ye light-response model to estimate the Pl of apple trees in Jinzhong Basin on Loess Plateau. The results show that the modified Jarvis (JarvisΔT-ΔC) model and the new Ye light-response model could estimate gl and Pl, respectively, with very high accuracy, with R2 values of 0.926 and 0.959 for the former, and 0.987 and 0.983 for the latter in 2019 and 2021, respectively. Then, we estimated the canopy stomatal conductance (gc) and photosynthetic rate (Pc) by first dividing the apple tree canopy into sunlit and shaded leaves and then summing the contribution of sunlit and shaded gl, Pl and leaf area index. Our efforts will be a valid reference for estimating the gc and Pc of other tree or crop species in the future.

Protein-rich yeast extract (®fermgard) has potential antioxidant and anti-aging activities.

There existed a deficiency in the research on the nutritional activities of microbial (yeast) active substances in antioxidant and anti-aging activities, although the research objects were concentrated in animals and plants in recent years. In this study, the anti-oxidant and anti-aging activities of protein-rich yeast extract (®fermgard) (YE) were investigated through Caenorhabditis elegans (C. elegans). The results indicated that YE could improve the lifespan and anti-stress ability by up-regulating the activities of antioxidant enzymes in C. elegans. Meanwhile, the mRNA transcriptional level of daf-16, skn-1 and sod-3 was significantly up-regulated. In addition, the composition and level of the gut microbiota and metabolite were modulated. YE exerts antioxidant and anti-aging activities by regulating the expression of anti-oxidation-related mRNA, gut microbiota and metabolites in C. elegans, providing a basis for exploring the deep mechanism of YE improving health. At the same time, it provides new ideas for the development of functional foods.

Ultra-high-performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry coupled with three-step data post-processing techniques for comprehensive profiling of the multiple components in Fufang Xianzhuli Ye.

INTRODUCTION: Fufang Xianzhuli (FXZL) Ye, a classical formula of traditional Chinese medicine, is composed of Succus Bambusae, Houttuyniae herba, Pinelliae Rhizoma, Zingiberis Rhizoma Recens, Eriobotryae Folium, Platycodonis Radix, and peppermint oil. For many years, FXZL has been primarily utilised in China to treat cough and phlegm. The chemical composition of FXZL has not been reported, which seriously affects the safety of the clinical application. OBJECTIVE: To establish a systematic method for rapidly classifying and recognising the chemical constituents in the FXZL for the safety of the clinical application. METHODS: An ultra-high performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry coupled with a three-step data post-processing strategy was developed to screen the chemical constituents of FXZL. RESULTS: In this experiment, the diagnostic ions in FXZL were classified into six main compounds. A total of 106 compounds were unambiguously identified in FXZL based on their retention times, accurate masses, and tandem mass spectrometry data. These include 11 chlorogenic acids, three flavonoids, eight sesquiterpenoids, six organic acids, 65 triterpenoid saponins, and 13 other compounds. CONCLUSION: The chemical composition of FXZL was identified and summarised, providing useful information for quality control and a basis for further exploration of its active ingredients in vivo.

Modified Technique for Small-Incision Lenticule Extraction: Ye's Swing Technique.

INTRODUCTION: This study aimed to evaluate the lenticule integrity and refractive outcomes of a new technique, Ye's swing technique, during small-incision lenticule extraction (SMILE). METHODS: This prospective study enrolled patients who underwent the SMILE procedure using a modified technique for lenticule dissection. Per the standard SMILE procedure, the cap cut was opened using a hook, and an anterior dissection was performed with a counterclockwise swing, from 8 to 12 o'clock. A posterior dissection was then performed by swinging counterclockwise, leaving a thin band of the peripheral rim undissected, from 8 to 4 o'clock. The counterclockwise swing was continued to separate the edges of the rim from 4 to 12 o'clock, after which microforceps were used to extract the lenticules. The primary outcome measures were safety and lenticule integrity at the end of the surgery, and the secondary outcome measure was efficacy. Changes in the ocular parameters from the preoperative visit to 1 month postoperative, including uncorrected and corrected distance visual acuity, manifest refraction, lenticule quality, and lenticule residual, were assessed using optical coherence tomography. RESULTS: A total of 246 patients (490 eyes) with myopia and myopic astigmatism were included in the present study. The dissected lenticules ranged in size from 52 to 148 µm. Postoperatively, the lenticule was completely and successfully extracted in all cases. There was no incisional edge tearing during lenticule separation. CONCLUSIONS: Ye's swing technique is a safe and effective procedure for lenticule dissection and refractive outcomes. We have now adopted this technique as our routine method for performing the SMILE procedure.

Protective role of casuarinin from Melastoma malabathricum against a mouse model of 5-fluorouracil-induced intestinal mucositis: Impact on inflammation and gut microbiota dysbiosis.

BACKGROUND: 5-FU-induced intestinal mucositis (FUIIM) is a common gastrointestinal side effect of chemotherapy, leading to gastric pain in clinical cancer patients. In a previous study, we demonstrated that neutrophil elastase (NE) inhibitors could alleviate FUIIM and manipulate the homeostasis of the gut microbiota. The root of Melastoma malabathricum, also called Ye-Mu-Dan, has been used as a traditional Chinese medicine for gastrointestinal disease. Water extract of the roots of M. malabathricum exhibits an inhibitory effect on NE, with an IC50 value of 9.13 µg/ml. PURPOSE: In this study, we aimed to isolate an anti-NE compound from the root of M. malabathricum and to determine the protective effect of the bioactive component on a mouse model of FUIIM with respect to tissue damage, inflammation, intestinal barrier dysfunction, and gut microbiota dysbiosis. METHODS: A water extract of the roots of M. malabathricum was prepared and its major bioactive compound, was identified using bioactivity-guided fractionation. The effects of samples on the inhibition of NE activity were evaluated using enzymatic assays. To evaluate the effects of the bioactive compound in an FUIIM animal model, male C57BL/6 mice treated with or without casuarinin (50 and 100 mg/kg/day, p.o.), and then received of 5-fluorouracil (50 mg/kg/day) intraperitoneally for 5 days to induce FUIIM. Histopathological staining was used to monitor the tissue damage, proliferation of intestinal crypts, and expression of tight junction proteins. The inflammation score was estimated by determining the levels of oxidative stress, neutrophil-related proteases, and proinflammatory cytokines in tissue and serum. The ecology of the gut microbiota was evaluated using 16S rRNA gene sequencing. RESULTS: Casuarinin had the most potent and selective effect against NE, with an IC50 value of 2.79 ± 0.07 µM. Casuarinin (100 mg/kg/day, p.o.) significantly improved 5-FU-induced body weight loss together with food intake reduction, and it also significantly reversed villus atrophy, restored the proliferative activity of the intestinal crypts, and suppressed inflammation and intestinal barrier dysfunction in the mouse model of FUIIM. Casuarinin also reversed 5-FU-induced gut microbiota dysbiosis, particularly the abundance of Actinobacteria, Candidatus Arthromitus, and Lactobacillus murinus, and the Firmicutes-to-Bacteroidetes ratio. CONCLUSION: This study firstly showed that casuarinin isolated from the root part of M. malabathricum could be used as a NE inhibitor, whereas it could improve FUIIM by modulating inflammation, intestinal barrier dysfunction, and gut microbiota dysbiosis. In summary, exploring anti-NE natural product may provide a way to find candidate for improvement of FUIIM.

Preparation, Identification, Molecular Docking Study and Protective Function on HUVECs of Novel ACE Inhibitory Peptides from Protein Hydrolysate of Skipjack Tuna Muscle.

To prepare bioactive peptides with high angiotensin-I-converting enzyme (ACE)-inhibitory (ACEi) activity, Alcalase was selected from five kinds of protease for hydrolyzing Skipjack tuna (Katsuwonus pelamis) muscle, and its best hydrolysis conditions were optimized using single factor and response surface experiments. Then, the high ACEi protein hydrolysate (TMPH) of skipjack tuna muscle was prepared using Alcalase under the optimum conditions of enzyme dose 2.3%, enzymolysis temperature 56.2 °C, and pH 9.4, and its ACEi activity reached 72.71% at 1.0 mg/mL. Subsequently, six novel ACEi peptides were prepared from TMPH using ultrafiltration and chromatography methods and were identified as Ser-Pro (SP), Val-Asp-Arg-Tyr-Phe (VDRYF), Val-His-Gly-Val-Val (VHGVV), Tyr-Glu (YE), Phe-Glu-Met (FEM), and Phe-Trp-Arg-Val (FWRV), with molecular weights of 202.3, 698.9, 509.7, 310.4, 425.6, and 606.8 Da, respectively. SP and VDRYF displayed noticeable ACEi activity, with IC50 values of 0.06 ± 0.01 and 0.28 ± 0.03 mg/mL, respectively. Molecular docking analysis illustrated that the high ACEi activity of SP and VDRYF was attributed to effective interaction with the active sites/pockets of ACE by hydrogen bonding, electrostatic force, and hydrophobic interaction. Furthermore, SP and VDRYF could significantly up-regulate nitric oxide (NO) production and down-regulate endothelin-1 (ET-1) secretion in HUVECs after 24 h treatment, but also abolish the negative effect of 0.5 µM norepinephrine (NE) on the generation of NO and ET-1. Therefore, ACEi peptides derived from skipjack tuna (K. pelamis) muscle, especially SP and VDRYF, are beneficial components for functional food against hypertension and cardiovascular diseases.

Complete mitochondrial genome of the Alpine Metacarpal-tubercled Toad Leptobrachella alpina (Amphibia, Anura, Megophryidae).

The complete mitochondrial genome of the Leptobrachella alpina Fei, Ye, and Li 1990, was assembled for the first time. The mitogenome of this species was 17,763 bp in length, containing 13 protein-coding genes, two ribosomal RNA genes (12S rRNA and 16S rRNA), 22 transfer RNA genes (tRNA), and a non-coding control region (D-loop). The base content of the mitogenome was that A, T, G, and C occupied 28.5%, 30.8%, 15.1%, and 25.6%, respectively. The phylogenetic analysis was conducted based on 17 complete mitogenome sequences of the family Megophryidae by the Bayesian inference approach. The phylogenetic tree suggested that Leptobrachium and Oreolalax clustered into a clade and formed a sister group with Leptobrachella. This work is critical for the further genetic research and conservation of this species.

Identification and fine genetic mapping of the golden pod gene (pv-ye) from the snap bean (Phaseolus vulgaris L.).

KEY MESSAGE: Using bulked segregant analysis combined with next-generation sequencing, we delimited the pv-ye gene responsible for the golden pod trait of snap bean cultivar A18-1. Sequence analysis identified Phvul.002G006200 as the candidate gene. The pod is the main edible part of snap beans (Phaseolus vulgaris L.). The commercial use of the pods is mainly affected by their color. Consumers seem to prefer golden pods. The aim of the present study was to identify the gene responsible for the golden pod trait in the snap bean. 'A18-1' (a golden bean cultivar) and 'Renaya' (a green bean cultivar) were chosen as the experimental materials. Genetic analysis indicated that a single recessive gene, pv-ye, controls the golden pod trait. A candidate region of 4.24 Mb was mapped to chromosome Pv 02 using bulked-segregant analysis coupled with whole-genome sequencing. In this region, linkage analysis in an F2 population localized the pv-ye gene to an interval of 182.9 kb between the simple sequence repeat markers SSR77 and SSR93. This region comprised 16 genes (12 annotated genes from the P. vulgaris database and 4 functionally unknown genes). Combined with transcriptome sequencing results, we identified Phvul.002G006200 as the potential candidate gene for pv-ye. Sequencing of Phvul.002G006200 identified a single-nucleotide polymorphism (SNP) in pv-ye. A pair of primers covering the SNP were designed, and the fragment was sequenced to screen 1086 F2 plants with the 'A18-1' phenotype. Our findings showed that among the 1086 mapped individuals, the SNP cosegregated with the 'A18-1' phenotype. The findings presented here could form the basis to reveal the molecular mechanism of the golden pod trait in the snap bean.

Amarogentin secoiridoid inhibits in vivo cancer cell growth in xenograft mice model and induces apoptosis in human gastric cancer cells (SNU-16) through the mediation of G2/M cell cycle arrest and PI3K/Akt signalling pathway.

The Editors of JBUON issue an Expression of Concern to 'Amarogentin secoiridoid inhibits in vivo cancer cell growth in xenograft mice model and induces apoptosis in human gastric cancer cells (SNU-16) through G2/M cell cycle arrest and PI3K/Akt signalling pathway', by Jian-Guo Zhao, Ling Zhang, Xiao-Jun Xiang, Feng Yu, Wan-li Ye, Dong-Ping Wu, Jian-Fang Wang, Jian-Ping Xiong, JBUON 2016;21(3):609-617; PMID:27569081. Following the publication of the above article, readers drew to our attention that part of the data was possibly unreliable. We sent emails to the authors with a request to provide the raw data to prove the originality, but received no reply. Therefore, as we continue to work through the issues raised, we advise readers to interpret the information presented in the article with due caution. We thank the readers for bringing this matter to our attention. We apologize for any inconvenience it may cause.

First Report of Anthracnose Caused by Colletotrichum gloeosporioides on Akebia trifoliata in China.

Akebia trifoliata (Thunberg) Koidzumi (three-leaf akebia), a climbing deciduous woody plant, grows wild in mountains of China and Japan. It has long been prized for its delicious sweet taste and medicinal value (Lu et al., 2019). Few pests and diseases reportedly affect this plant (Ye et al., 2013), but with more commercial planting of A. trifoliata in China, symptoms of anthracnose on leaves and fruits have increased. Between December 2018 and May 2019, typical anthracnose symptoms were first observed on A. trifoliata grown in Wuhan, China, with an incidence up to 15%. Diseased leaves exhibited irregular gray-brown spots with dark brown edges, and dark brown undersides, substantially affecting photosynthesis and growth. As disease progressed, white mycelium appeared on stems causing stem rot and fruit drop. Several round or needle-shaped dark brown spots formed on fruit peel, coalescing into irregular, slightly sunken blotches. Under high humidity, the whole fruit turned brown and the spots were covered by white mycelia, greatly affecting the fruits' ornamental quality. To isolate the pathogen, 5-mm2 pieces of symptomatic tissue from 10 infected leaves and fruits were surface-disinfected for 90 s in 1% sodium hypochlorite then 30 s in 75% ethanol, rinsed twice with sterile water, then incubated on potato dextrose agar (PDA, Oxoid) at 25°C under 12 h light/dark photoperiod. Pure cultures were obtained from hyphal tips of each colony. Initially, colonies produced white mycelia, turning gray after 5 days. The isolates produced abundant hyaline, single celled, straight and cylindrical conidia, with mean size 10.35 to 15.58 × 3.46 to 5.69 µm. Morphological characteristics were generally consistent with those of Colletotrichum gloeosporioides (Cannon et al. 2012). Genomic DNA of three isolates was extracted for PCR amplification of the internal transcribed spacer (ITS) region, and ß-tubulin (TUB2), and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) genes (Weir et al. 2012). BLAST search identified all sequences (GenBank accession nos. MT451846 to MT451848 for ITS, MT573957 to MT573959 for TUB2, and MT573960 to MT573962 for GAPDH) as 100% matches to C. gloeosporioides (Penz.) Penz. & Sacc. CBS 112999 strain (JQ005152 for ITS, JQ005587 for TUB2, JQ005239 for GAPDH) (Damm et al. 2009). Identification was confirmed by maximum likelihood phylogenetic analysis using MEGA7 . To evaluate pathogenicity, isolates were inoculated onto one side of 10 wounded healthy leaves of 1-year-old pot-grown A. trifoliata plants and 10 nearly mature fruits, with 10 µl of conidial suspension (106/ml) and colonized PDA pieces (5 mm diam.) from 7-day-old cultures of the fungus in Petri dishes; control sides received 10 µl sterile distilled water and sterile agar pieces. The test was performed twice. After incubation at 25°C, 70% humidity under 12 h fluorescent illumination/12 h dark for 5 days, similar spots were observed on all inoculated leaves and fruits. Controls remained asymptomatic. The re-isolated pathogen was identified as C. gloeosporioides by biological characteristics and sequencing analysis, indicating that C. gloeosporioides was a causal agent of anthracnose of A. trifoliata. Anthracnose caused by C. acutatum has been reported on A. trifoliata in Japan (Kobayshi et al. 2004). To our knowledge, this is the first report of C. gloeosporioides found on Akebia species. The new disease primarily reduces the quality and yield of A. trifoliata. Effective measures should be taken to manage this disease. Funding: This study was supported by the National Natural Science Foundation of China (31701974; 31901980), Science and technology program funded by Wuhan Science and Technology Bureau (2018020401011307). References: Lu, W.L., et al. 2019. J. Ethnopharmacol. 234:204. Ye, Y.F., et al. 2013. Plant Dis. 97:1659. Kobayshi, Y., et al. 2004. J. Gen. Plant Pathol. 70:295. Cannon, P.F., et al. 2012. Stud. Mycol. 73:181. Weir, B.S., et al. 2012. Stud. Mycol. 73:115. Damm, U., et al. 2009. Fungal Divers. 39:45.

Cloning expression and immunogenicity analysis of inhibin gene in Ye Mule Aries sheep.

BACKGROUND: Ye Mule Aries sheep is one of the most important sheep breeds in Xinjiang, China. This breed is well adapted to harsh environmental conditions and displays strong disease resistance, fast growth, and high cold tolerance. To analyze the clonal expression and immunogenicity of the Ye Mule Aries sheep inhibin gene, total RNA was extracted from sheep ovarian tissue and used as a template to generate a eukaryotic expression vector and study inhibin immunogenicity. METHODS: Primers were designed to amplify the inhibin A gene via polymerase chain reaction and the amplified product was cloned between the ScalI and EcoRI restriction sites of the expression vector pEGFP-N1 to construct a recombinant plasmid, pEGFP-INHα. Following the validation of successful cloning, the pEGFP-INHα plasmid was transfected into BHK cells to verify expression in eukaryotes and subsequently utilized as an antigen in rabbits. Rabbits were tested for anti-inhibin antibodies and serum follicle-stimulating hormone (FSH) concentrations. RESULTS: The analysis of the INHα gene sequence revealed that INHα is 1109 bp long and is translated to an approximately 40 KDa protein. Bioinformatics approach indicated that the INHα gene is highly conserved between organisms. Immunization with the eukaryotic expression vector, pEGFP-INHα, which expresses the INHα gene elicited immune response and generatigeneration on of anti-INHα antibody. The antibody had a significant regulatory effect on the serum concentration of FSH in rabbits and led to higher levels of FSH, indicating increased ovary function. CONCLUSIONS: The present work resulted in a successful construction of eukaryotic expression plasmid pEGFP-INHα and verified the immunogenicity of this highly conserved protein. Further, the expression of pEGFP-INHα was shown to have a significant impact on the secretion of FSH, indicating a potential regulatory role in ovarian function. In conclusion, our current findings can serve as a working model for studying the effect of INHα on the breeding performance of Ye Mule Aries sheep, providing a novel strategy to improve their reproduction rates.

[Study on active components of Fufang Huangbai Ye for diabetic foot treatment by UPLC-LTQ-Orbitrap-MS and network pharmacology].

Chemical constituents of the Fufang Huangbai Ye( FFHB) were analyzed and identified by UPLC-ESI-LTQ-OrbitrapMS. The analysis was performed on an Waters HSS T3 reverse phase column( 2. 1 mm×100 mm,1. 8 µm). The mobile phase consisting of 0. 1% aqueous formic acid( A) and acetonitrile( B) was used with gradient elution,and the flow rate was 0. 3 mL·min~(-1).Based on the information of the accurate mass,the multistage fragment ions,the mass spectrometric data of the standard substance and the relative reference literature,the structure of the chemical constituents in FFHB were identified. Based on the identified compounds,network pharmacology study,including target prediction,functional enrichment,and molecular docking was applied to screen out the main active substances for treatment of diabetes foot and explore the potential mechanism. The results showed that a total of 138 compounds were identified,including 28 alkaloids,16 flavonoids,11 phenylethanoid glycosides,9 cycloolefins,11 cyclohexylethanol derivatives,28 phenolic acids and derivatives,3 lignans,4 terpenes,28 volatile oils and the others. Further,36 active substances for diabetes foot were screened out,and the functional enrichment showed the potential mechanism of FFHB were mainly seven functional items including inflammatory response,growth factor activity. This study combining the UPLC-LTQ-Orbitrap-MS technology and the network pharmacology provide a useful reference and basis for active compounds,quality control markers and the pharmacological mechanism of FFHB for diabetic foot treatment.

Jie Du Tong Ye San Prevents N-Nitrosomethylbenzylamine-Induced Esophageal Carcinogenesis via Inhibition of Inflammation and Proliferation.

Jie du tong ye san (JDTYS), a traditional Chinese herbal formula, has been used for cancer adjuvant therapy in clinical use and has been shown to be effective in cancer patients. However, the mechanism of JDTYS is still unclear. Therefore, the aim of the present study is to investigate the chemopreventive effects of JDTYS for esophageal squamous cell carcinoma (ESCC) and to clarify the potential mechanism. N-nitrosomethylbenzylamine (NMBA)-induced rat esophageal carcinogenesis was used to evaluate the effect of JDTYS in vivo. Rats were treated with NMBA 3 times per week, for a total of 5 weeks. Rats in the treated groups were given JDTYS for 35 weeks. When rats were euthanized, esophageal tissue and blood were collected to evaluate the effects of JDTYS. The pathological grading of the rat esophageal preneoplastic lesions was classified and statistically analyzed. The protein levels of c-Jun and Ki67 were determined by immunohistochemistry. In addition, inflammation markers nuclear factor kappa B (NF-κB), cyclooxygenase-2 (COX-2), and the cluster of differentiation molecule 11B (CD11B) were also determined by immunohistochemistry. Moreover, the expression of COX-2 and Pentraxin 3 (PTX3) in rat serum was determined by enzyme-linked immunosorbent assay (ELISA). JDTYS could inhibit the formation of NMBA-induced esophageal preneoplastic lesions. JDTYS could downregulate the expression of proliferation related proteins Ki67 and c-Jun. Moreover, inflammation related proteins NF-κB, COX-2, and CD11B were inhibited and PTX3 was increased by JDTYS. In all, JDTYS is a promising chemopreventive formula against esophageal carcinogenesis by regulating inflammation and inhibiting cell proliferation.

Effects of Xingpi Kaiyu Fang on ATP, Na/K-ATPase, and Respiratory Chain Complexes of Hippocampus and Gastrocnemius Muscle in Depressed Rats.

OBJECTIVE: To clarify the effectiveness and mechanism of the Chinese herbal formula Xingpi Kaiyu Fang (XPKYF) which is composed of American ginseng (Xi-Yang-shen), Radix curcumae (Yu-Jin), Acori tatarinowii rhizoma (Shi-Chang-pu), and Hypericum perforatum (Guan-Ye-lian-qiao) in depressed rats. METHODS: The rat model of depression was established by chronic unpredictable mild stress (CUMS) method for 6 weeks. Rats were randomly divided into six groups: control group, CUMS group, CUMS+XPKYF (3.6g/kg/d, 7.2g/kg/d, 14.4g/kg/d) groups, and CUMS+sertraline (4.5mg/kg/d) group. The sucrose preference test and the forced swimming test were performed to assess the rats' depression behavior. Mitochondrial ultrastructure was observed by transmission electron microscope and adenosine triphosphate (ATP) content, sodium potassium ATPase (Na/K-ATPase) activity, and mitochondrial respiratory chain complexes activities in hippocampus and gastrocnemius muscle were measured at the 14th and 42nd day. RESULTS: Rats subjected to six weeks of CUMS exhibited decreased sucrose preference ratio and prolonged immobility time. CUMS reduced ATP content in hippocampus, decreased Na/K-ATPase activity and respiratory chain complex I, III, and IV activities in hippocampus and gastrocnemius muscle, and damaged mitochondrial ultrastructure of hippocampus and gastrocnemius muscle. XPKYF at 14.4g/kg, the efficacy trend of which was better than the other drug groups, could prevent the stress-induced depressed behavior changes, inhibit the decrease of Na/K-ATPase activity in hippocampus, inhibit the decrease of respiratory chain complex III activities in hippocampus and gastrocnemius muscle, and protect mitochondria from ultrastructural damage. CONCLUSIONS: Energy deficiency and damaged mitochondrial ultrastructure were found in hippocampus and gastrocnemius muscle of depressed rats established by CUMS. XPKYF could partly reverse alterations in ATP, Na/K-ATPase, and respiratory chain complexes of hippocampus and gastrocnemius muscle and protect mitochondria from ultrastructural damage. This provides another experimental evidence for the clinical application of XPKYF in the treatment of depression.

Transplanted mouse liver stem cells at different stages of differentiation ameliorate concanavalin A-induced acute liver injury by modulating Tregs and Th17 cells in mice.

Acute liver failure (ALF) is a disease with a considerably high mortality rate that still lacks a safe and effective treatment. Transplantation of liver stem cells (LSCs) has been considered to be a promising therapeutic alternative for ALF since LSCs have been shown to be involved in immunomodulation and functional reconstruction of the liver. Our present study evaluated and compared the protective effects of the two mouse LSC lines, YE and R5, as well as those of adult mouse hepatocyte (HC), on concanavalin A (ConA)-induced acute liver injury. YE and R5 cells were analyzed by microscopy, functional assays, and gene expression. We confirmed that YE and R5 cells were undifferentiated cells that had partial hepatocytic functions and a potential to differentiate into hepatocytes. YE cells has characteristics of LSCs at the early stage of differentiation, whereas the differentiation stage of R5 cells was later than that of YE cells. Subsequently, YE, R5, and HC cells were intraperitoneally transplanted into three groups of mice, followed by injection of ConA through the tail vein of each mouse at 12 h later. Blood tests, histology, flow cytometry, and quantitative PCR were then used to evaluate the therapeutic effects of the cell transplantations at 24 h after ConA injections. Compared with that of the ConA control group, YE, R5, and HC cells reduced the expression of alanine transaminase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBIL) in serum and alleviated the degree of hepatic necrosis. Moreover, transplantation of these cells induced more regulatory T cells (Tregs) and less T-helper 17 (Th17) cells in the liver and spleen, and also promoted the expression of forkhead box protein 3 (Foxp3) and interleukin (IL)-10; in contrast, these transplantations induced various degrees of inhibition in the expression of retinoic acid-related orphan receptor γt (RORγt), IL-17A, IL-17F, and tumor necrosis factor-α (TNF-α). The protective effects of YE and R5 cells were significantly stronger than those of HC cells, and YE cells at the earlier differentiation stage than that of R5 cells exhibited the strongest protective effects. These results demonstrate that mouse LSCs at different stages of differentiation alleviate ConA-induced acute liver injury in mice by modulating Tregs, Th17 cells, and cytokine secretion.

Bisphenol A exposure alters placentation and causes preeclampsia-like features in pregnant mice involved in reprogramming of DNA methylation of WNT2.

Preeclampsia leads to adverse outcomes for pregnant women. Bisphenol A (BPA) is an environmental endocrine disruptor and has been shown to be positively associated with increased risk of preeclampsia in human studies. We investigated whether BPA exposure causes preeclampsia-like features in pregnant mice and the associated underlying mechanisms. Experiments were performed in animal models and cell cultures. In pregnant mice, BPA-exposed mice exhibited preeclampsia-like features including hypertension, disruption of the circulation, and the placental angiogenesis biomarkers fms-related tyrosine kinase 1 and placenta growth factor, and glomerular atrophy; urinary protein was not affected. These preeclampsia-like features correlated with increased retention of smooth muscle cells and reduced vessel areas at the junctional zone of the placenta. In addition, there were disrupted expression of invasion-related genes including increased tissue inhibitors of metalloproteinases, decreased metalloproteinases, and Wnt family member WNT2/ß-catenin, which correlated with increased DNA methylation in its promoter region and upregulation of DNA methyltransferase (Dnmt)1. BPA exposure impeded the interaction between the human cytotrophoblast cell line, HTR-8/SVneo, and endothelium cells. BPA exposure down-regulated WNT2 expression, and elevated the DNA methylation of WNT2; these results were consistent with in vivo observations. Inhibition of DNMT in HTR-8/SVneo cells resulted in reduced DNA methylation and increased expression of WNT2. Taken together, these data demonstrate that BPA exposure alters trophoblast cell invasion and causes abnormal placental vessel remodeling, both of which lead to the development of preeclampsia-like features in pregnant mice. Our results suggest that this phenomenon involves the epigenetic reprogramming and down-regulation of WNT2 mediated by DNMT1.-Ye, Y., Tang, Y., Xiong, Y., Feng, L., Li, X. Bisphenol A exposure alters placentation and causes preeclampsia-like features in pregnant mice involved in reprogramming of DNA methylation of WNT2.