[Ligusticum cycloprolactam inhibits IL-1ß-induced apoptosis and inflammation of rat chondrocytes via HMGB1/TLR4/NF-κB signaling pathway].

Chondrocytes are unique resident cells in the articular cartilage, and the pathological changes of them can lead to the occurrence of osteoarthritis(OA). Ligusticum cycloprolactam(LIGc) are derivatives of Z-ligustilide(LIG), a pharmacodynamic marker of Angelica sinensis, which has various biological functions such as anti-inflammation and inhibition of cell apoptosis. However, its protective effect on chondrocytes in the case of OA and the underlying mechanism remain unclear. This study conducted in vitro experiments to explore the molecular mechanism of LIGc in protecting chondrocytes from OA. The inflammation model of rat OA chondrocyte model was established by using interleukin-1ß(IL-1ß) to induce. LIGc alone and combined with glycyrrhizic acid(GA), a blocker of the high mobility group box-1 protein(HMGB1)/Toll-like receptor 4(TLR4)/nuclear factor-kappa B(NF-κB) signaling pathway, were used to intervene in the model, and the therapeutic effects were systematically evaluated. The viability of chondrocytes treated with different concentrations of LIGc was measured by the cell counting kit-8(CCK-8), and the optimal LIGc concentration was screened out. Annexin V-FITC/PI apoptosis detection kit was employed to examine the apoptosis of chondrocytes in each group. The enzyme-linked immunosorbent assay(ELISA) was employed to measure the expression of cyclooxygenase-2(COX-2), prostaglandin-2(PGE2), and tumor necrosis factor-alpha(TNF-α) in the supernatant of chondrocytes in each group. Western blot was employed to determine the protein levels of B-cell lymphoma-2(Bcl-2), Bcl-2-associated X protein(Bax), caspase-3, HMGB1, TLR4, and NF-κB p65. The mRNA levels of HMGB1, TLR4, NF-κB p65, and myeloid differentiation factor 88(MyD88) in chondrocytes were determined by real-time fluorescent quantitative PCR(RT-qPCR). The safe concentration range of LIGc on chondrocytes was determined by CCK-8, and then the optimal concentration of LIGc for exerting the effect was clarified. Under the intervention of IL-1ß, the rat chondrocyte model of OA was successfully established. The modeled chondrocytes showed increased apoptosis rate, promoted expression of COX-2, PGE2, and TNF-α, up-regulated protein levels of Bax, caspase-3, HMGB1, TLR4, and NF-κB p65 and mRNA levels of HMGB1, TLR4, NF-κB p65, and MyD88, and down-regulated protein level of Bcl-2. However, LIGc reversed the IL-1ß-induced changes of the above factors. Moreover, LIGc combined with GA showed more significant reversal effect than LIGc alone. These fin-dings indicate that LIGc extracted and derived from the traditional Chinese medicine A. sinensis can inhibit the inflammatory response of chondrocytes and reduce the apoptosis of chondrocytes, and this effect may be related to the HMGB1/TLR4/NF-κB signaling pathway. The pharmacological effect of LIGc on protecting chondrocytes has potential value in delaying the progression of OA and improving the clinical symptoms of patients, and deserves further study.

Construction of a clinical prediction model for the impact of acupuncture on pregnancy outcomes in poor ovarian response (POR) patients based on a patient registry research platform. / åŸºäºŽç— ä¾‹æ³¨å†Œç™»è®°ç ”ç©¶å¹³å°æž„å»ºé’ˆç¸å¯¹åµå·¢ä½Žååº”æ‚£è€ å¦Šå¨ ç»“å±€çš„ä¸´åºŠé¢„æµ‹æ¨¡åž‹.

OBJECTIVES: To construct a clinical prediction model for the impact of acupuncture on pregnancy outcomes in poor ovarian response (POR) patients, providing insights and methods for predicting pregnancy outcomes in POR patients undergoing acupuncture treatment. METHODS: Clinical data of 268 POR patients (2 cases were eliminated) primarily treated with "thirteen needle acupuncture for Tiaojing Cuyun (regulating menstruation and promoting pregnancy)" was collected from the international patient registry platform of acupuncture moxibustion (IPRPAM) from September 19, 2017 to April 30, 2023, involving 24 clinical centers including Acupuncture-Moxibustion Hospital of China Academy of Chinese Medical Sciences. LASSO and univariate Cox regression were used to screen factors influencing pregnancy outcomes, and a multivariate Cox regression model was established based on the screening results. The best model was selected using the Akaike information criterion (AIC), and a nomogram for clinical pregnancy prediction was constructed. The prediction model was evaluated using receiver operating characteristic (ROC) curves and calibration curves, and internal validation was performed using the Bootstrap method. RESULTS: (1) Age, level of anti-Müllerian hormone (AMH), and total treatment numbers of acupuncture were independent predictors of pregnancy outcomes in POR patients receiving acupuncture (P<0.05). (2) The AIC value of the best subset-Cox multivariate model (560.6) was the smallest, indicating it as the optimal model. (3) The areas under curve (AUCs) of the clinical prediction model after 6, 12, 24, and 36 months treatment were 0.627, 0.719, 0.770, and 0.766, respectively, and in the validation group, they were 0.620, 0.704, 0.759, and 0.765, indicating good discrimination and repeatability of the prediction model. (4) The calibration curve showed that the prediction curve of the clinical prediction model was close to the ideal model's prediction curve, indicating good calibration of the prediction model. CONCLUSIONS: The clinical prediction model for the impact of acupuncture on pregnancy outcomes in POR patients based on the IPRPAM platform has good clinical application value and provides insights into predicting pregnancy outcomes in POR patients undergoing acupuncture treatment.

Bacterial diversity of herbal rhizospheric soils in Ordos desert steppes under different degradation gradients.

Objectives: This study explored the effects of different degradation gradients on bacterial diversity in the rhizospheric soils of herb plants. Methods: The alpha diversity, species composition and correlations of bacterial communities in the rhizospheric soils of herb plants were studied using metagenomics 16SrDNA gene high-throughput sequencing. Results: The diversity of bacterial communities in the rhizospheric soils of herb plants differed during the degradation of desert steppes. An analysis of bacterial community alpha diversity indices showed the bacterial diversity and species evenness of rhizospheric soils were best in moderately degraded desert steppes. Among all samples, a total of 43 phyla, 133 classes, 261 orders, 421 families, 802 genera and 1,129 species were detected. At the phylum level, the predominant bacterial phyla were: Actinobacteria, Proteobacteria, Acidobacteria, Gemmatimonadetes, Chloroflexi, Planctomycetes and Bacteroidetes. At the genus level, the predominant bacterial genera were: RB41, Sphingomonas, WD2101_soil_group_unclassified, Pseudomonas and Actinomyces. The relative abundance of unknown genera was very large, which deserves further research. At the phylum and genus levels, the species abundance levels under slight and moderate degradation were significantly higher than those under extreme degradation. Correlation network diagrams showed there were many nodes in both slightly deteriorated and moderately deteriorated soils, and the node proportions were large and mostly positively correlated. These results indicate the bacterial communities in rhizospheric soils under slight or moderate deterioration are relatively stable. The rhizospheric soil microbes of desert steppes can form a stable network structure, allowing them to adequately respond to environmental conditions. Conclusions: The bacterial communities in the rhizospheric soils of herb plants differ between different degradation gradients. The species number, abundance and diversity of bacterial communities in rhizospheric soils are not directly correlated with degree of degradation. The abundance, species diversity and species abundance of bacterial communities in the rhizospheric soils of moderately degraded desert steppes are the highest and most stable. The soil bacterial diversity is lowest in severely degraded desert steppes.

Association of biopsy core number and location with pain in patients undergoing a transperineal prostate biopsy under local anaesthesia: a secondary analysis of the APROPOS trial.

BACKGROUND: APROPOS was a multicentre, randomized, blinded trial focus on investigating the perineal nerve block versus the periprostatic block in pain control for men undergoing a transperineal prostate biopsy. In the analysis reported here, the authors aimed to evaluate the association of biopsy core count and location with pain outcomes in patients undergoing a transperineal prostate biopsy under local anesthesia. METHODS: APROPOS was performed at six medical centers in China. Patients with suspected prostate cancer were randomized to receive either a perineal nerve block or a periprostatic block (1:1), followed by a transperineal prostate biopsy. The secondary analysis outcomes were the worst pain experienced during the prostate biopsy and postbiopsy pain at 1,6, and 24 h. RESULTS: Between 12 August 2020 and 20 July 2022, a total of 192 patients were randomized in the original trial, and 188 were involved in this analysis, with 94 patients per group. Participants had a median (IQR) age of 68 (63-72) and a median (IQR) prostate volume of 42.51 (30.04-62.84). The patient population had a median (IQR) number of biopsy cores of 15 (12-17.50), and 26.06% of patients had a biopsy cores count of more than 15. After adjusting the baseline characteristics, the number of biopsy cores was associated with the worst pain during the biopsy procedure in both the perineal nerve block group ( ß 0.19, 95% CI: 0.12-0.26, P <0.001) and the periprostatic block group ( ß 0.16, 95% CI: 0.07-0.24, P <0.001). A similar association was also evident for the postbiopsy pain at 1, 6, and 24 h. A lesser degree of pain in both groups at any time (r range -0.57 to -0.01 for both groups) was associated with biopsy cores from the peripheral zone of the middle gland, while other locations were associated with a higher degree of pain. In addition, the location of the biopsy core had less of an effect on pain during the biopsy (r range -0.01-0.25 for both groups) than it did on postbiopsy pain (r range -0.57-0.60 for both groups). CONCLUSIONS: In this secondary analysis of a randomized trial, biopsy core count and location were associated with pain in patients undergoing a transperineal prostate biopsy under local anesthesia. These results may be helpful for making clinical decisions about the anesthetic approach for scheduled transperineal prostate biopsies.

Discovery of deoxyandrographolide and its novel effect on vascular senescence by targeting HDAC1.

Aconitum carmichaelii (Fuzi) is a traditional Chinese medicine that has been widely used in the clinic to save the dying life for over several thousand years. However, the medicinal components of Fuzi in treating vascular senescence (VS) and its potential mechanism remain unclear. In this study, a network pharmacology method was used to explore the possible components and further validated by experiments to get a candidate compound, deoxyandrographolide (DA). DA restrains aging biomarkers, such as p16, p21, γH2A.X, and p53 in vitro and in vivo blood co-culture studies. Histone deacetylase 1 (HDAC1), mouse double minute2 (MDM2), cyclin-dependent kinase 4, and mechanistic target of rapamycin kinase (mTOR) are predicted to be the possible targets of DA based on virtual screening. Subsequent bio-layer interferometry results indicated that DA showed good affinity capability with HDAC1. DA enhances the protein expression of HDAC1 in the angiotensin II-induced senescence process by inhibiting its ubiquitination degradation. Loss of HDAC1 by CRISPR/Cas9 leads to the disappearance of DA's anti-aging property. The enhancement of HDAC1 represses H3K4me3 (a biomarker of chromosomal activity) and improves chromosome stability. RNA sequencing results also confirmed our hypothesis. Our evidence illuminated that DA may achieve as a novel compound in the treatment of VS by improving chromosome stability.

Dietary supplementation of pyridoxine can enhance the growth performance and improve the protein, lipid utilization efficiency of mandarin fish (Siniperca chuatsi).

This study aimed to assess the effect of pyridoxine supplementation in the mandarin fish diet on growth performance, protein and lipid metabolism, and liver and intestinal histology. Mandarin fish were fed six diets with different levels of pyridoxine (2.67 mg/kg (control), 4.41 mg/kg, 6.57 mg/kg, 10.25 mg/kg, 17.93 mg/kg, 33.12 mg/kg diet) for 8 weeks, and samples were collected for analysis. The findings demonstrated that feeding mandarin fish a diet with 6.57 mg/kg pyridoxine led to a significant increase in weight gain rate (WGR), protein efficiency ratio (PER), whole-body crude protein, whole-body crude lipid, serum protein, cholesterol (CHO), triacylglycerol (TG), high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), and alkaline phosphatase (ALP), as well as significantly lower serum glucose (GLU) and feed conversion ratio (FCR), compared to the control group (P < 0.05). Furthermore, we found a significant upregulation of the relative expression of genes associated with hepatic lipid oxidation and synthesis (hl, lpl, pparα, cpt1, cs, srebp1, and fas) and proteolysis (ast, alt, and gdh) in fish fed a diet containing 6.57 mg/kg pyridoxine (P < 0.05). Regarding the histological analysis, we observed a notable decrease in the quantity of intestinal mucus-secreting cells when the fish fed a diet containing 10.25 mg/kg pyridoxine (P < 0.05). These findings suggest that dietary pyridoxine supplementation promotes mandarin fish growth by improving the efficiency of protein and lipid utilization. Additionally, we used a broken-line regression analysis to estimate the optimal dietary pyridoxine requirement for mandarin fish in the range of 6.17-6.41 mg/kg based on WGR, FCR, and PER.

Anammox-Mediated Hydroxyapatite Granules: Physicochemical Properties, 3D Hierarchy, and Biofilm Thickness.

Biomineralization inspired the development of simultaneous biological transformations and chemical precipitation for simultaneous nitrogen removal and phosphorus recovery from wastewater, which could compensate for the incapacity of phosphorus management in the new biological route of anaerobic ammonium oxidation (anammox). In this study, we strengthened anammox-mediated biomineralization by long-term feeding of concentrated N, P, and Ca substrates, and a self-assembled matrix of anammox bacteria and hydroxyapatite (HAP) was fabricated in a granular shape, defined as HAP-anammox granules. HAP was identified as the dominant mineral using elemental analysis, X-ray diffraction, and Raman spectroscopy. The intensive precipitation of HAP resulted in a higher inorganic fraction and substantially improved settleability of anammox biomass, which facilitated HAP precipitation by acting as nucleation and metabolically elevated pH. By using X-ray microcomputed tomography, we visually represented the hybrid texture of interwoven HAP pellets and biomass, the core-shell layered architecture of different-sized HAP-anammox granules, and their homogeneously regulated thickness of the outer biofilm (from 118 to 635 µm). This unique architecture endows HAP-anammox granules with outstanding settleability, active biofilm, and tightly bonded biofilm with the carrier, which may explain the excellent performance of these HAP-anammox granules under various challenging operational conditions in previous studies.

[Neuroprotective effect of tetramethylpyrazine on mice after spinal cord injury].

This study aims to investigate the neuroprotective effect of tetramethylpyrazine on mice after spinal cord injury and its mechanism. Seventy-five female C57BL/6 mice were randomly divided into 5 groups, namely, a sham operation group, a model group, a tetramethylpyrazine low-dose group(25 mg·kg~(-1)), a tetramethylpyrazine medium-dose group(50 mg·kg~(-1)), and a tetramethylpyrazine high-dose group(100 mg·kg~(-1)), with 15 mice in each group. Modified Rivlin method was used to establish the mouse model of acute spinal cord injury. After 14 d of tetramethylpyrazine intervention, the motor function of hind limbs of mice was evaluated by basso mouse scale(BMS) and inclined plate test. The levels of inflammatory cytokines tumor necrosis factor-α(TNF-α), interleukin-6(IL-6), and interleukin-1ß(IL-1ß) in the spinal cord homogenate were determined by enzyme-linked immunosorbent assay(ELISA). Hematoxylin-eosin(HE) staining was used to observe the histology of the spinal cord, and Nissl's staining was used to observe the changes in the number of neurons. Western blot and immunofluorescence method were used to detect the expression of glial fibrillary acidic protein(GFAP) and C3 protein. Tetramethylpyrazine significantly improved the motor function of the hind limbs of mice after spinal cord injury, and the BMS score and inclined plate test score of the tetramethylpyrazine high-dose group were significantly higher than those of the model group(P<0.01). The levels of TNF-α, IL-6, and IL-1ß in spinal cord homogenate of the tetramethylpyrazine high-dose group were significantly decreased(P<0.01). After tetramethylpyrazine treatment, the spinal cord morphology recovered, the number of Nissl bodies increased obviously with regular shape, and the loss of neurons decreased. As compared with the model group, the expression of GFAP and C3 protein was significantly decreased(P<0.05,P<0.01) in tetramethylpyrazine high-dose group. In conclusion, tetramethylpyrazine can promote the improvement of motor function and play a neuroprotective role in mice after spinal cord injury, and its mechanism may be related to inhibiting inflammatory response and improving the hyperplasia of glial scar.

Synthesis, Structure Revision, and Anti-inflammatory Activity Investigation of Putative Blumeatin.

Blumeatin, reported herein, bearing two hydroxyl groups at C3' and C5' of ring B, is isolated from the traditional Chinese medicine Blumea balsamifera. But the isolation procedure of blumeatin from plants has limitations of prolonged duration and high cost. A procedure featuring Lewis acid-catalyzed ring closure and chiral resolution via Schiff base intermediates is provided here to prepare optically pure blumeatin and its R-isomer efficiently. Furthermore, the structure revision of putative blumeatin based on a logically synthetic procedure and NMR spectroscopic analysis was conducted. The 1D and 2D NMR data analysis unambiguously confirmed our proposal that the reported blumeatin structure has been misassigned as it corresponds to sterubin, which contains two hydroxyl groups at C3' and C4' of ring B. Finally, the results of the ear-swelling test exhibited that synthetic (±)-blumeatin and (±)-sterubin had moderate anti-inflammatory activity which was less than that of (-)-sterubin.

The extract of Curcumae Longae Rhizoma suppresses angiogenesis via VEGF-induced PI3K/Akt-eNOS-NO pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Curcumae Longae Rhizoma (CLR) is a safe natural herbal medicine, and which has been widely used for centuries as functional food and health products, but its effects on angiogenesis and related underlying mechanism remain unclear. AIM OF THE STUDY: The abnormal angiogenesis is closely related with various diseases, and therefore the precise control of angiogenesis is of great importance. The well-known angiogenic factor, vascular endothelial growth factor (VEGF), mediates angiogenesis and induces multiple signalling pathways via binding to VEGF receptor (VEGFR). The attenuation of VEGF-triggered angiogenic-related signalling pathways may relieve various diseases through suppression of angiogenesis. Here, we aimed to elucidate that CLR extract could exert striking anti-angiogenic activities both in vitro and in vivo. MATERIALS AND METHODS: The viability of human umbilical vascular endothelial cell (HUVEC) was examined by LDH and MTT assays. Migrative and invasive ability of the endothelial cells were independently evaluated by wound healing and transwell assays. The activities of CLR extract on in vitro angiogenesis was tested by tube formation assay. In vivo vascularization was determined by using zebrafish embryo model in the present of CLR extract. Western blotting was applied to determine the phosphorylated levels of VEGFR2, PI3K, AKT and eNOS. Besides, the levels of nitric oxide (NO) and reactive oxygen species (ROS) were separately evaluated by Griess assay and 2'7'-dichlorofluorescein diacetate reaction. In addition, the cell migrative ability of cancer cell was estimated by using cultured human colon carcinoma cells (HT-29 cell line), and immunofluorescence assay was applied to evaluate the effect of CLR extract on nuclear translocation of NF-κB p65 subunit in the VEGF-treated HT-29 cultures. RESULTS: CLR extract significantly suppressed a series of VEGF-mediated angiogenic responses, including endothelial cell proliferation, migration, invasion, and tube formation. Moreover, CLR extract reduced in vivo sub-intestinal vessel formation in zebrafish embryo model. Mechanistically, the extract of CLR attenuated the VEGF-triggered signalling, as demonstrated by decreased level of phosphorylated VEGFR2 and subsequently inactivated its downstream regulators, e.g. phospho-PI3K, phospho-AKT and phospho-eNOS. The production of NO and formation of ROS were markedly inhibited in HUVECs. Furthermore, CLR extract suppressed cell migration and NF-κB translocation in cultured HT-29 cells. CONCLUSIONS: These preclinical findings demonstrate that the extract of CLR remarkably attenuates angiogenesis and which has great potential as a natural drug candidate with excellent anti-angiogenic activity.

Anammox upflow hybrid reactor: Nitrogen removal performance and potential for phosphorus recovery.

Echoing to the call of recovering high-value-added chemicals from wastewater and achieving carbon-neutral operation in wastewater treatment, an anammox upflow hybrid reactor was successfully applied for nitrogen removal, and the potential for phosphorus recovery was put forward. Moreover, the spatial pattern of removal capacities, and distribution of biomass and HAP precipitates were recognized and demonstrated as height-oriented. The intensity of HAP precipitates was highly consistent with the amount of anammox biomass and the relative abundance of the Candidatus Kuenenia, indicating that HAP formation was encouraged by the anammox reaction itself and heterogeneous nucleation induced by organic matters (proteins and polysaccharides). The fixed bed also played an important role in immobilizing the anammox biomass, secreted organic matrix, and HAP precipitates. This finding also provoked the thought that in the anammox process, HAP precipitation was more achievable, effective and practicable using the fixed-carrier system.

Co-load of silybin and doxorubicin by MoS2 nanosheets for synergetic chemotherapy and photothermal therapy of lung cancer / 药学学报

The active ingredient of traditional Chinese medicine, silybin (SBN), can inhibit the proliferation of cancer cells and enhance the anticancer effect of doxorubicin (DOX). However, due to non-targeting and short half-life of SBN and DOX, as well as different administration routes and pharmacokinetic processes, this combination drug cannot act on the tumor in the set order, seriously eliminating the synergistic effect between them and limiting the effect in vivo. Therefore, we intended to construct a nano-delivery system based on molybdenum disulfide (MoS2), modified by polyethylene glycol (PEG) and sialic acid (SA), and co-loaded with SBN and DOX. The system induced the release of combined drugs under the dual-stimulation of pH and near infra-red (NIR), increased the free concentration of intracellular drugs, so as to achieve the synergistic effect between them. The animal welfare and experimental procedures were in accordance with the regulations of the Animal Ethics Committee of Fujian University of Traditional Chinese Medicine. MoS2-PEG-SA-SBN/DOX circulated in vivo, and effectively accumulated at tumor sites through enhanced permeability and retention effect (EPR) and SA-mediated active targeting. Under near infrared light irradiation, MoS2-PEG-SA-SBN/DOX realized the combination of synergistic chemotherapy and photothermal therapy for tumor, thus achieving excellent anti-tumor effect in vivo. This study can provide a new idea and strategy for the clinical treatment of lung cancer. Taken together, MoS2-PEG-SA-SBN/DOX can offer a new idea and strategy for the clinical treatment of lung cancer.

Role of macrophages in heart failure and traditional Chinese medicine intervention / 中国中药杂志

As the disease with high morbidity and mortality in the world, heart failure affects the development of human society. Due to its complicated pathology and limited treatment options, it is urgent to discover new disease targets and develop new treatment strategies. As innate immune cells accompanied by the evolution of heart failure, macrophages play an important role in cardiac homeostasis and stress. In recent years, the role of macrophages in the heart has attracted more and more attention as a potential target for heart failure intervention, and the research on cardiac macrophages has made important progress. Traditional Chinese medicine(TCM) has significant effects on regulating inflammatory response, treating heart failure, and maintaining homeostasis. In this article, researches on the functions of cardiac macrophages and application of TCM were reviewed from the source and classification of cardiac macrophages and the relationship of macrophages and cardiac inflammation, myocardial fibrosis, cardiac angiogenesis, and cardiac electrical conduction, which provided a basis for further basic research and clinical applications.

Ameliorative Effect of Chitosan Oligosaccharides on Hepatic Encephalopathy by Reshaping Gut Microbiota and Gut-Liver Axis.

This study investigated the influence of chitosan oligosaccharides (COSs) on a thioacetamide-induced hepatic encephalopathy (HE) Wistar rat model. COS treatment statistically reduced the false neurotransmitters and blood ammonia in HE rats, along with the suppression of oxidative stress and inflammation. The disbalanced gut microbiota was detected in HE rats by 16S rDNA sequencing, but the abundance alterations of some intestinal bacteria at either the phylum or genus level were at least partly restored by COS treatment. According to metabolomics analysis of rat feces, six metabolism pathways with the greatest response to HE were screened, several of which were remarkably reversed by COS. The altered metabolites might serve as a bridge for the alleviated HE rats treated with COS and the enhanced intestinal bacterial structure. This study provides novel guidance to develop novel food or dietary supplements to improve HE diseases due to the potential beneficial effect of COS on gut-liver axis.

N-linked glycoproteomic profiling in esophageal squamous cell carcinoma.

BACKGROUND: Mass spectrometry-based proteomics and glycomics reveal post-translational modifications providing significant biological insights beyond the scope of genomic sequencing. AIM: To characterize the N-linked glycoproteomic profile in esophageal squamous cell carcinoma (ESCC) via two complementary approaches. METHODS: Using tandem multilectin affinity chromatography for enrichment of N-linked glycoproteins, we performed N-linked glycoproteomic profiling in ESCC tissues by two-dimensional gel electrophoresis (2-DE)-based and isobaric tags for relative and absolute quantification (iTRAQ) labeling-based mass spectrometry quantitation in parallel, followed by validation of candidate glycoprotein biomarkers by Western blot. RESULTS: 2-DE-based and iTRAQ labeling-based quantitation identified 24 and 402 differentially expressed N-linked glycoproteins, respectively, with 15 in common, demonstrating the outperformance of iTRAQ labeling-based quantitation over 2-DE and complementarity of these two approaches. Proteomaps showed the distinct compositions of functional categories between proteins and glycoproteins with differential expression associated with ESCC. Western blot analysis validated the up-regulation of total procathepsin D and high-mannose procathepsin D, and the down-regulation of total haptoglobin, high-mannose clusterin, and GlcNAc/sialic acid-containing fraction of 14-3-3ζ in ESCC tissues. The serum levels of glycosylated fractions of clusterin, proline-arginine-rich end leucine-rich repeat protein, and haptoglobin in patients with ESCC were remarkably higher than those in healthy controls. CONCLUSION: Our study provides insights into the aberrant N-linked glycoproteome associated with ESCC, which will be a valuable resource for future investigations.

A Novel Delivery System of RGD-HSA Loaded GEM/CUR Nanoparticles for the Treatment of Pancreatic Cancer Therapy.

Introduction: Pancreatic cancer is one of the most common malignant tumors and is characterized by high malignancy, occult incidence and poor prognosis. Traditional chemotherapy drugs have limited efficacy and strong side effects. Therefore, there is an urgent need for a better treatment of the malignancy. Methods: The prepared arginine glycine peptide (RGD)-human serum albumin (HSA)-Gemcitabine (GEM)/Curcumin (CUR) nanoparticles (NPs) were characterized for physicochemical properties, stability and in vitro release. Comparisons of HSA-GEM/CUR NPs and RGD-HSA-GEM/CUR NPs regarding tissue distributions and pharmacodynamics were also carried out using mice as the animal models. Results: Transmission electron micrographs showed that RGD peptide-conjugated HSA-NPs had an irregular surface, good dispersion (PDI=0.139±0.03) and a uniform size distribution (Mean PS=115.6±5.7 nm). The ζ-potential was -17.3 mV. As regards in vitro release, non RGD modified NPs showed a faster release rate in 24 hours, yielding a release amount of 75% for GEM and 72% for CUR. RGD-HSA-GEM/CUR NPs exhibited 67% of accumulated release of GEM (63% for CUR) in 24 hours. This may be due to the HSA chain covering the surface of NPs, which hindered the drug release. The cytotoxicity of GEM/CUR co-loaded NPs was significantly higher than that of single-drug NPs (P < 0.05). In vivo study results indicated that RGD-HSA-GEM/CUR NPs had notable targeting effect on subcutaneous tumors, with a potential to actively deliver drugs to tumor tissues. Conclusion: In this study, we prepared RGD-HSA-GEM/CUR NPs that had both good water solubility and tumor-targeting property. The results also showed that the RGD modified NPs had advantages in increasing GEM/CUR concentration at tumor sites and reducing its distribution in peripheral organs.

Centranthera grandiflore alleviates alcohol-induced oxidative stress and cell apoptosis.

Alcohol liver disease (ALD) has become a global threat to human health. It is associated with a wide range of liver diseases including alcohol fatty liver, steatosis, fibrosis and cirrhosis, and finally leads to liver cancer and even death. Centranthera grandiflora is a traditional Chinese medicinal herb commonly used to treat ALD, but no research about its mechanism is available. This study evaluated the hepatoprotective effect and mechanism of C. grandiflora against alcohol-induced liver injury in mice. We found that the ethanol extracts of C. grandiflora (CgW) alleviated the alcohol-induced liver injury, enhanced the levels of antioxidant enzymes, and reduced the amount of lipid peroxides. CgW also affected cell apoptosis by inhibiting the activity of Bax, cleaved-caspase 3 and cleaved-caspase 9, and increasing the activity of Bcl-2. In conclusion, the results showed that CgW can effectively improve ALD through alleviating oxidative stress and inhibiting cell apoptosis for the first time. This study suggested that C. grandiflora is a promising herbal medicine for ALD treatment.

The inclusion of extract from aerial part of Scutellaria baicalensis in feeding of pearl gentian grouper (Epinephelus fuscoguttatus♀ × Epinephelus lanceo-latus♂) promotes growth and immunity.

The root of Scutellaria baicalensis (Scutellaria Radix) has been used as herbal medicine for years in China; however, its stem and leaf (aerial part) are considered as waste. The water extract of aerial part of S. baicalensis, named as SBA, having anti-microbial property has been applied in fish aquaculture. To extend the usage of SBA in fish feeding, SBA was employed to feed pearl gentian grouper (a hybrid of Epinephelus fuscoguttatus♀ × Epinephelus lanceolatus♂), and subsequently the total fish output, the levels of digestive enzymes and inflammatory cytokines were determined. Feeding the fish with different doses of SBA for two months, the body length and weight were significantly increased by 5%-10%. In parallel, the expressions of alkaline phosphatase and growth-related factors in bone, liver and muscle of SBA-fed fish were doubled, which could account the growth promoting effect of SBA. Besides, the activity of digestive enzyme, lipase, and the expressions of anti-inflammatory cytokines were markedly stimulated by 2-3 times under the feeding of 3% SBA-containing diet. The results indicated the growth promoting activity of SBA in culture of pearl gentian grouper, as well as the effect of SBA in strengthening the immunity. These beneficial effects of SBA feeding can increase the total yield of pearl gentian grouper in aquaculture. Thus, the re-cycle of waste products during the farming of S. baicalensis herb in serving as fish feeding should be encouraged.

Compensatory growth and understory soil stoichiometric features of Hippophae rhamnoides at different stubble heights.

Background: This study was aimed to explore the compensatory growth ability and influence mechanism of Hippophae rhamnoides at the decaying phase in feldspathic sandstone areas of Ordos, and clarify the stubble height when the compensatory growth ability of H. rhamnoides was the strongest. Methods: The H. rhamnoides forests in the decaying phase from an exposed feldspathic sandstone zone of Ordos were chosen. The compensatory growth ability of H. rhamnoides at stubble height of 0 cm (S1), 10 cm (S2), 15 cm (S3), 20 cm (S4) and control (CK) was investigated with H. rhamnoides forests at the decaying stage in the exposed feldspathic sandstone areas of Ordos. Relationships of compensatory growth ability of H. rhamnoides and understory soil properties with understory soil stoichiometric features as well as the response mechanism to stubble height were explored. Results: (1) Overcompensatory growth of H. rhamnoides in feldspathic sandstone areas occurred at all stubble heights. Especially, the plant height compensation index (1.45) and biomass compensation index (1.25) at the stubble height of 15 cm were both larger compared with other stubbling treatments. These results indicate the stubble height of 15 cm can well promote the growth of the ground part of H. rhamnoides. (2) All stubble heights significantly affected the contents and eco-stoichiometric ratios of soil organic carbon (SOC), total nitrogen (TN), total phosphorus (TP) in understory soils, but the influence rules differed. SOC, TN, and TP contents at all stubble heights were larger than those of the control, and maximized at the stubble height of 15 cm. The carbon(C): phosphorus(P) ratio, and nitrogen (N):(P) ratio after stubbling treatments were all lower compared with the control, and minimized to 19.52 and 1.84 respectively at the stubble height of 15 cm. (3) The understory C:N:P stoichiometric ratio of H. rhamnoides in feldspathic sandstone areas is jointly affected by compensatory growth, stubble height, and soil physicochemical properties. The total explanation rate determined from RDA is 93.1%. The understory soil eco-stoichiometric ratio of H. rhamnoides is mainly affected by soil moisture content (contribution of 87.6%) and total porosity (7.9%), indicating soil moisture content is the most influential factor. The findings will offer some new clues for eco-construction and theoretically underlie soil-water loss administration.

Analysis of the current status and related factors of oral nutritional supplements intake among 18-79 years old in Beijing in 2017 / 中华流行病学杂志

Objective: To understand the current status of taking nutrient supplements for residents aged 18 to 79 years old in Beijing and its related factors. Methods: Data were gathered from the 2017 Beijing Non-communicable and Chronic Disease Surveillance Program. Multiple classified cluster sampling method was used, and participants aged 18-79 were sampled from 16 districts. The questionnaire included chronic diseases and related risk factors, health knowledge, and oral nutritional supplements within 12 months. Multivariate logistic regression models were established to analyze associated factors that affect the intake of nutrient supplements. Results: The weighted prevalence of supplements use was 13.1% among 12 696 subjects within the past 12 months. The proportions of multivitamins (4.7%), B vitamins (4.5%), and folic acid (3.2%) were higher. The prevalence of supplement use of young people (18-39 years old) and the elderly (60-79 years old) was higher than middle-aged people (40-59 years old) (χ2=54.09, P<0.001). Except for the age group of 70-79 years old, the consumption rate of women was significantly higher than that of men (P<0.05). After adjusting age and sex, among patients with hypertension, diabetes, or dyslipidemia, the control rates of blood pressure, glucose and lipids of patients who take nutrient supplements were higher than those who do not (P<0.05). And participants who took nutrient supplements had a more heightened awareness rate of health knowledge, such as the hazards of smoking and second-hand smoke, and recommended amount of salt per day (P<0.001). The multi-factor logistic analysis found that nutrient supplement-related factors include women, old age, higher education level, living in urban, insufficient physical activity, sleeping problems, active physical examination, blood pressure control among patients, and health knowledge (P<0.05). Conclusions: The factors of nutrient supplements use were related to sex, age, education level, health status, and health literacy. We should pay attention to key populations and guide them to establish the correct concept of taking nutrient supplements.