Bioactive materials from berberine-treated human bone marrow mesenchymal stem cells promote alveolar bone regeneration by regulating macrophage polarization.

Alveolar bone regeneration has been strongly linked to macrophage polarization. M1 macrophages aggravate alveolar bone loss, whereas M2 macrophages reverse this process. Berberine (BBR), a natural alkaloid isolated and refined from Chinese medicinal plants, has shown therapeutic effects in treating metabolic disorders. In this study, we first discovered that culture supernatant (CS) collected from BBR-treated human bone marrow mesenchymal stem cells (HBMSCs) ameliorated periodontal alveolar bone loss. CS from the BBR-treated HBMSCs contained bioactive materials that suppressed the M1 polarization and induced the M2 polarization of macrophages in vivo and in vitro. To clarify the underlying mechanism, the bioactive materials were applied to different animal models. We discovered macrophage colony-stimulating factor (M-CSF), which regulates macrophage polarization and promotes bone formation, a key macromolecule in the CS. Injection of pure M-CSF attenuated experimental periodontal alveolar bone loss in rats. Colony-stimulating factor 1 receptor (CSF1R) inhibitor or anti-human M-CSF (M-CSF neutralizing antibody, Nab) abolished the therapeutic effects of the CS of BBR-treated HBMSCs. Moreover, AKT phosphorylation in macrophages was activated by the CS, and the AKT activator reversed the negative effect of the CSF1R inhibitor or Nab. These results suggest that the CS of BBR-treated HBMSCs modulates macrophage polarization via the M-CSF/AKT axis. Further studies also showed that CS of BBR-treated HBMSCs accelerated bone formation and M2 polarization in rat teeth extraction sockets. Overall, our findings established an essential role of BBR-treated HBMSCs CS and this might be the first report to show that the products of BBR-treated HBMSCs have active effects on alveolar bone regeneration.

Rheological properties and microstructure of wheat flour dough systems with enzyme-hydrolyzed mashed potatoes.

The interest in incorporating potatoes into wheat dough is increasing. However, potatoes exhibit significant viscosity during thermal processing, affecting product processing and quality. This study aims to find an effective method to reduce the viscosity of mashed potatoes. We aimed to compare the effects of different enzymes (α-amylase, ß-amylase, and flavourzyme) and concentrations (0.01%, 0.05%, and 0.1%) on the micromorphology and rheological properties of mashed potatoes and potato-wheat dough. The impact of flavourzyme was the most significant (p<0.05). When enzyme concentration increased, viscosity decreased, and the degree of structural damage, indicated by increased porosity. Notably, the addition of flavourzyme can increase the content of sweet and umami free amino acids, improving the flavor of mashed potatoes. The scanning electron microscopy and confocal laser scanning microscopy images of potato-wheat dough revealed that enzyme-hydrolyzed mashed potatoes had improved homogeneity, reestablished the dough continuity, and strengthened the three-dimensional structure comprising proteins and starch. Notably, flavourzyme demonstrated the most significant effect on enhancing the protein-starch network structure. This was attributed to the exposure of functional groups resulting from protein hydrolysis, facilitating interaction with starch molecules. Our findings indicate that the addition of 0.1% flavourzyme (500 LAPU/g, pH 5.5, 55 ± 2°C, 30 min treated) was the most effective in reducing viscosity and reconstructing the gluten network. Enzymatic hydrolysis plays a vital role in the production of high-quality potato products, with particular importance in the baking industry, where flavourzyme exhibits significant potential. PRACTICAL APPLICATION: Enzymatic hydrolysis plays a vital role in the production of high-quality potato products, with particular importance in the baking industry, where flavourzyme exhibits significant potential.

A new andrographolide derivative ADA targeting SIRT3-FOXO3a signaling mitigates cognitive impairment by activating mitophagy and inhibiting neuroinflammation in Apoe4 mice.

BACKGROUND: Alzheimer's disease (AD) is one of the most common neurodegenerative diseases and mitophagy deficit was identified as the typical abnormality in early stage of AD. The neuroprotective effect of andrographolide (AGA) has been confirmed, anda acetylated derivative of AGA (3,14,19-triacetylandrographolide, ADA) was considered to have stronger efficacy. PURPOSE: The current study aims to investigate the impact of ADA on cognitive ability in a sporadic AD model and explore its potential mechanism. STUDY DESIGN/ METHODS: Apoe4 mouse was adopted for evaluating the impact of AGA on cognitive impairment through a serious of behavioral tests. The molecular mechanism of ADA involved in mitophagy and neuroinflammation was investigated in detailby Western blot, ELISA, immunofluorescence and transmission electron microscopy in Apoe4 mice, as well as Apoe4-transfected BV2 cells and HT22 cells. RESULTS: ADA application significantly improved cognitive impairment of Apoe4 mice, and lessened Aß load and neuronal damage, which has stronger activity than its prototype AGA. Accumulated mitophagy markers LC3II, P62, TOM20, PINK1 and Parkin, and decreased mitophagy receptor BNIP3 in hippocampus of Apoe4 mice were greatly reversed after ADA treatment. Meanwhile, ADA promoted the recruitment of BNIP3 to mitochondria, and the transport of damaged mitochondria to lysosome, indicating that disturbed mitophagy in AD mice was restored by ADA. Inhibited SIRT3 and FOXO3a in Apoe4 mice brains were elevated after ADA treatment. ADA also lightened the neuroinflammation caused by NLRP3 inflammasome activation. Additionally, damaged mitophagy and/or activated NLRP3 inflammasome were also observed in BV2 cells and HT22 cells transfected with Apoe4, all of which were rescued by ADA incubation. Noteworthily, SIRT3 inhibitor 3-TYP could abolish the impact of ADA on mitophagy and NLRP3 inflammasome in vitro. CONCLUSION: ADA exerted stronger cognition-enhancing ability in relative to AGA, and ADA could repaire mitophagy deficiency via SIRT3-FOXO3a pathway, and subsequently inhibite NLRP3 inflammasome to mitigate AD pathology.

Anthraquinone metabolites isolated from the rhizosphere soil Streptomyces of Panax notoginseng (Burk.) F. H. Chen target MMP2 to inhibit cancer cell migration.

ETHNOPHARMACOLOGICAL RELEVANCE: Panax notoginseng (Burk.) F. H. Chen belongs to the Araliaceae family. It has been used by traditional Chinese people in Northeast Asia for centuries as an antidiabetic, antioxidant, antitumor agent, etc. Endophytic or rhizospheric microorganisms play key roles in plant defense mechanisms, and they are essential in the discovery of pharmaceuticals and valuable new secondary metabolites. In particular, endophytic or rhizospheric microorganisms of traditional medicinal plants. AIM OF THE STUDY: To discover valuable new secondary metabolites from rhizosphere soil Streptomyces sp. SYP-A7185 of P. notoginseng, and to explore potential bioactivities and targets of metabolites protrusive function. MATERIALS AND METHODS: The metabolites were obtained via column chromatography and identified by multiple spectroscopic analyses. The antitumor, antioxidant, antibacterial, and antiglycosidases effects of isolated metabolites were tested using 3-[4,5-dimethythiazol-2-yl]-2,5-diphenyltetazolium bromide (MTT), 2,2-diphenyl-1-picrylhydrazyl (DPPH), 96-well turbidimetric, and α-glucosidase inhibitory assays. The potential antitumor targets were predicted through network pharmacological approaches. The interactions between metabolites and target were verified by molecular docking and biolayer interferometry (BLI) assay. The effects of cancer cells migration were detected through wound healing assays in A549 and MCF-7. Other cellular validation experiments including reverse transcription-quantitative PCR (RT‒qPCR) and western blotting (WB) were used to confirm the hypothesis of network pharmacology. RESULTS: Five different chemotypes of anthraquinone derivatives (1-10), including six new compounds (3, 6-10), were identified from Streptomyces sp. SYP-A7185. Compounds 1-6 and 9 displayed moderate to strong cytotoxicity on five human cancer cell lines (A549, HepG2, MCF-7, MDA-MD-231, and MGC-803). Moreover, matrix metalloproteinase-2 (MMP2) were predicted as a potential antitumor target of metabolites 1-6 and 9 by comprehensive network pharmacology analysis. Later, BLI assays revealed strong intermolecular interactions between MMP2 and antitumor metabolites, and molecular docking results showed the interaction of metabolites 1-6 and 9 with MMP2 was dependent on the crucial amino acid residues of LEU-83, ALA-84, LEU-117, HIS-131, PRO-135, GLY-136, ALA-140, PRO-141, TYR-143, and THR-144. These results implied that metabolites (1-6 and 9) might inhibit cancer cell migration besides cancer cell proliferation. After that, the cell wound healing assay showed that the cell migration processes were also inhibited after the treatments of compounds 1 and 3 in A549 and MCF-7 cells. In addition, the RT‒qPCR and WB results demonstrated that the gene expression levels of MMP2 were decreased after the treatment with compounds 1 and 3 in A549 and MCF-7 cells. Besides, compound 2 displayed moderate antioxidant activity (EC50, 27.43 µM), compounds 3 and 6 exhibited moderate antibacterial activity, and compound 3 inhibited α-glucosidase with an IC50 value of 13.10 µM. CONCLUSIONS: Anthraquinone metabolites, from rhizosphere soil Streptomyces sp. of P. notoginseng, possess antitumor, antioxidant, antibacterial, and antiglycosidase activities. Moreover, metabolites 1 and 3 inhibit cancer cells migration through downregulating MMP2.

Enhanced phosphate adsorption studies on several metal-modified aluminum sludge: preparation optimization, adsorption behavior, and mechanistic insight.

To solve the problems such as water eutrophication caused by excess phosphorus, the potential residual value of aluminum sludge was fully exploited and its phosphate adsorption capacity was further improved. In this study, twelve metal-modified aluminum sludge materials were prepared by co-precipitation method. Among them, Ce-WTR, La-WTR, Y-WTR, Zr-WTR, and Zn-WTR showed excellent adsorption capacity for phosphate. The adsorption performance of Ce-WTR on phosphate was twice that of the native sludge. The enhanced adsorption mechanism of metal modification on phosphate was investigated. The characterization results showed that the increase in specific surface area after metal modification was 9.64, 7.5, 7.29, 3, and 1.5 times, respectively. The adsorption of phosphate by WTR and Zn-WTR was in the accordance with Langmuir model, while the others were more following the Freundlich model (R2 > 0.991). The effects of dosage, pH, and anion on phosphate adsorption were investigated. The surface hydroxyl groups and metal (hydrogen) oxides played an important role in the adsorption process. The adsorption mechanism involves physical adsorption, electrostatic attraction, ligand exchange, and hydrogen bonding. This study provides new ideas for the resource utilization of aluminum sludge and theoretical support for preparing novel adsorbents for efficient phosphate removal.

Pharmacophore-driven identification of human glutaminyl cyclase inhibitors from foods, plants and herbs unveils the bioactive property and potential of Azaleatin in the treatment of Alzheimer's disease.

Alzheimer's disease (AD) is the leading cause of disabilities in old age and a rapidly growing condition in the elderly population. AD brings significant burden and has a devastating impact on public health, society and the global economy. Thus, developing new therapeutics to combat AD is imperative. Human glutaminyl cyclase (hQC), which catalyzes the formation of neurotoxic pyroglutamate (pE)-modified ß-amyloid (Aß) peptides, is linked to the amyloidogenic process that leads to the initiation of AD. Hence, hQC is an essential target for developing anti-AD therapeutics. Here, we systematically screened and identified hQC inhibitors from natural products by pharmacophore-driven inhibitor screening coupled with biochemical and biophysical examinations. We employed receptor-ligand pharmacophore generation to build pharmacophore models and Phar-MERGE and Phar-SEN for inhibitor screening through ligand-pharmacophore mapping. About 11 and 24 hits identified from the Natural Product and Traditional Chinese Medicine databases, respectively, showed diverse hQC inhibitory abilities. Importantly, the inhibitors TCM1 (Azaleatin; IC50 = 1.1 µM) and TCM2 (Quercetin; IC50 = 4.3 µM) found in foods and plants exhibited strong inhibitory potency against hQC. Furthermore, the binding affinity and molecular interactions were analyzed by surface plasmon resonance (SPR) and molecular modeling/simulations to explore the possible modes of action of Azaleatin and Quercetin. Our study successfully screened and characterized the foundational biochemical and biophysical properties of Azaleatin and Quercetin toward targeting hQC, unveiling their bioactive potential in the treatment of AD.

Engineered Hydroxyapatite Nanoadjuvants with Controlled Shape and Aspect Ratios Reveal Their Immunomodulatory Potentials.

Hydroxyapatite (HAP) has been formulated as adjuvants in vaccines for human use. However, the optimal properties required for HAP nanoparticles to elicit adjuvanticity and the underlying immunopotentiation mechanisms have not been fully elucidated. Herein, a library of HAP nanorods and nanospheres was synthesized to explore the effect of the particle shape and aspect ratio on the immune responses in vitro and adjuvanticity in vivo. It was demonstrated that long aspect ratio HAP nanorods induced a higher degree of cell membrane depolarization and subsequent uptake, and the internalized particles elicited cathepsin B release and mitochondrial reactive oxygen species generation, which further led to pro-inflammatory responses. Furthermore, the physicochemical property-dependent immunostimulation capacities were correlated with their humoral responses in a murine hepatitis B surface antigen immunization model, with long aspect ratio HAP nanorods inducing higher antigen-specific antibody productions. Importantly, HAP nanorods significantly up-regulated the IFN-γ secretion and CD107α expression on CD8+ T cells in immunized mice. Further mechanistic studies demonstrated that HAP nanorods with defined properties exerted immunomodulatory effects by enhanced antigen persistence and immune cell recruitments. Our study provides a rational design strategy for engineered nanomaterial-based vaccine adjuvants.

[Acupuncture based on meridian diagnosis for chronic atrophic gastritis].

OBJECTIVE: To compare the efficacy between acupoint selection of meridian diagnosis and regular acupoint selection for chronic atrophic gastritis (CAG). METHODS: A total of 70 cases of CAG were randomly divided into an observation group (35 cases, 5 cases dropped off) and a control group (35 cases, 5 dropped off). In the observation group, according to the hand diagnosis of meridians and the results of 80-channels energy determinator, based on the principle of child-mother relation acupoint combination, the luo-connecting point and back-shu points were added for excess syndrome, and the yuan-primary point, front-mu points and he-sea point of foot meridians were added for deficiency syndrome; in addition, the acupoints of the eight extraordinary meridians were added based on the nature of acupoints. In the control group, Zhongwan (CV 12), Neiguan (PC 6), Zusanli (ST 36) and Gongsun (SP 4) were selected as the primary acupoints, and additional acupoints were added according to syndrome differentiation. The two groups were treated twice a week (Tuesday and Thursday, respectively), totally for 6 months. Six months after treatment, the follow-up was conducted. The clinical symptom score, gastroenteropathy patient reported outcomes (PRO) scale score before treatment, after treatment and during follow-up as well as the score of pathological changes of gastric mucosa before and after treatment were compared between the two groups. RESULTS: After treatment and during follow-up, the clinical symptom scores and gastroenteropathy PRO scale scores were decreased in the two groups (P<0.01, P<0.001); at the follow-up, the gastroenteropathy PRO scale score in the observation group was lower than that in the control group (P<0.01). After treatment, the scores of pathological changes of gastric mucosa in the two groups were decreased (P<0.01), and the score in the observation group was lower than that in the control group (P<0.05). CONCLUSION: The acupoint selection of meridian diagnosis is superior to regular acupoint selection for CAG, which has better efficacy, more significant improvement on gastric mucosa pathology, and more stable long-term effect.

α-Pyrones, secondary metabolites from fungus Cephalotrichum microsporum and their bioactivities.

Cephalotrichum microsporum (SYP-F 7763) was a fungus isolated from the rhizosphere soil of traditional Chinese medicine Panax notoginseng. The EtOAc extract of Cephalotrichum microsporum cultivated on sterilized moistened-rice medium was separated by various chromatographic techniques, which yielded 11 metabolites (1-11) of this fungus. On the basis of the widely spectroscopic data, the chemical structures of isolated metabolites were determined, most of which were α-pyrones, including 5 compounds (4-7, and 10) unreported. In the anti-bacterial bioassay, compound 1 displayed significant inhibitory effects on three pathogenic bacteria, MR S. aureus, S. aureus, and B. cereus. α-Pyrones 2, 3, and 5-7 also displayed moderate inhibitory effects on MR S. aureus, S. aureus, and B. subtilis, which could be the major anti-bacterial constituents of Cephalotrichum microsporum. Additionally, compounds 1, 4, and 5 displayed significant cytotoxicity on five human cancer cell lines, with the IC50 values < 20 µM, which are more effective than positive control 5-fluorouracil. Therefore, α-pyrones were important secondary metabolites of Cephalotrichum microsporum, which displayed anti-bacterial and anti-tumor activities.

New antimicrobial compounds produced by endophytic Penicillium janthinellum isolated from Panax notoginseng as potential inhibitors of FtsZ.

A total of 180 fungal isolates, belonging to 20 genera and 47 species, were obtained from the roots, stems and leaves of Panax notoginseng. One isolate, the endophytic fungus Penicillium janthinellum SYPF 7899, displayed the strongest antibacterial activity and was studied for its production of secondary metabolites. In total, three new compounds, including rotational isomers 1a, 1b and 2 were isolated from the solid cultures of P. janthinellum, as well as eight known compounds (3-10). These structures were determined on the basis of 1D, 2D NMR and electronic circular dichroism (ECD) spectroscopic analyses as well as theoretical calculations. Compound 1 exhibited significant inhibitory activities against Bacillus subtilis and Staphylococcus aureus with MIC values of 15 and 18 µg/ml, respectively. The other compounds showed moderate or weak activities. In addition, morphological observation showed the rod-shaped cells of B. subtilis growing into long filaments, which reached 1.5- to 2-fold of the length of the original cells after treatment with compound 1. The coccoid cells of S. aureus exhibited a similar response and swelled to a 2-fold volume after treatment with compound 1. In silico molecular docking was explored to study the binding interactions between the compounds and the active sites of filamentous temperature-sensitive protein Z (FtsZ) from B. subtilis and S. aureus. Compound 1a, 1b and 2 showed high binding energies, strong H-bond interactions and hydrophobic interactions with FtsZ. Based on the antimicrobial activities, cellular phenotype observation and docking studies, compound 1 is considered to be a promising antimicrobial inhibitor of FtsZ.

GlnR positive transcriptional regulation of the phosphate-specific transport system pstSCAB in Amycolatopsis mediterranei U32.

Amycolatopsis mediterranei U32 is an important industrial strain for the production of rifamycin SV. Rifampicin, a derivative of rifamycin SV, is commonly used to treat mycobacterial infections. Although phosphate has long been known to affect rifamycin biosynthesis, phosphate transport, metabolism, and regulation are poorly understood in A. mediterranei. In this study, the functional phosphate transport system pstSCAB was isolated by RNA sequencing and inactivated by insertion mutation in A. mediterranei U32. The mycelium morphology changed from a filamentous shape in the wild-type and pstS1+ strains to irregular swollen shape at the end of filamentous in the ΔpstS1 strain. RT-PCR assay revealed that pstSCAB genes are co-transcribed as a polycistronic messenger. The pstSCAB transcription was significantly activated by nitrate supplementation and positively regulated by GlnR which is a global regulator of nitrogen metabolism in actinomycetes. At the same time, the yield of rifamycin SV decreased after mutation (ΔpstS1) compared with wild-type U32, which indicated a strong connection among phosphate metabolism, nitrogen metabolism, and rifamycin production in actinomycetes.

Two New Alkaloids from Fusarium tricinctum SYPF 7082, an Endophyte from the Root of Panax notoginseng.

Panax notoginseng (Araliaceae) is a famous traditional Chinese medicine mainly cultivated in Yunnan and Guangxi provinces of China. Two new alkaloids, rigidiusculamide E (1) and [-(α-oxyisohexanoyl-N-methyl-leucyl)2-] (2), together with two known ones, (-)-oxysporidinone (3) and (-)-4,6'-anhydrooxysporidinone (4) were isolated from the mycelia culture of Fusarium tricinctum SYPF 7082, an endophytic fungus obtained from the healthy root of P. notoginseng. Their structures were determined on the basis of extensive spectroscopic analyses. Compounds 1-4 were tested for their inhibitory effects against NO production on Murine macrophage cell line, and the new compound 2 showed significant inhibitory activity on NO production with the IC50 value of 18.10 ± 0.16 µM.

An endophytic Fungi of Ginkgo biloba L. produces antimicrobial metabolites as potential inhibitors of FtsZ of Staphylococcus aureus.

A total of 58 fungal isolates, belonging to 24 genera, were obtained from the leaves, stems and roots of Ginkgo biloba L.. Among them, one endophytic fungal strain, Penicillium cataractum SYPF 7131, displayed the strongest antibacterial activity. Four new compounds (1-4) were isolated from the strain fermentation broth together with four known compounds (5-8). These structures were determined on the basis of 1D and 2D NMR and [Rh2(OCOCF3)4]-induced electronic circular dichroism (ECD) spectroscopic analyses. All the isolated compounds were screened for their in vitro antimicrobial activities. Compound 3 and 4 showed moderate inhibitory activity against Staphylococcus aureus. Compound 7 exhibited significant inhibitory activity against S. aureus with MIC value of 10 µg/mL. Further, the in silico molecular docking studies of the active compounds was used to explore the binding interactions with the active site of filamentous temperature-sensitive protein Z (FtsZ) from Staphylococcus aureus. The docking results revealed that compounds 3, 4 and 7 showed high binding energies, strong H-bond interactions and hydrophobic interactions with FtsZ from S. aureus validating the observed antimicrobial activity. Based on antimicrobial activities and docking studies, compounds 3, 4 and 7 were identified as promising antimicrobial lead molecules.

Four new hybrid polyketide-terpenoid metabolites from the Penicillium sp. SYPF7381 in the rhizosphere soil of Pulsatilla chinensis.

A search for cytotoxic agents from cultures of the Penicillium sp., isolated from the rhizosphere soil of Pulsatilla chinensis, led to the isolation of four new hybrid polyketide-terpenoid metabolites (1-4), together with fourteen known compounds (5-18). Using a bioassay-guided fractionation approach, eighteen compounds were obtained from the ethyl acetate extract of this fungus. Structure elucidation was achieved by extensive analysis of spectroscopic data (1D/2D NMR, HRESIMS and IR). The absolute configurations of compounds 1-4 were determined by means of electronic circular dichroism (ECD) calculation. Compounds 1-4, 7-9, 11, 12, 14 and 17 were tested for their cytotoxicity against HL-60, THP-1 and Caco2 cell lines. Compound 1 showed potent cytotoxic capability against HL-60, THP-1 and Caco2 cell with IC50 values of 3.4µM, 4.3µM, 10.5µM, and compound 2 showed significant inhibiting activities against HL-60 cell line and THP-1 cell line (IC50=7.9µM, 11.3µM, respectively), using 5-fluorouracil as the positive drug with IC50 values of 6.4µM, 4.4µM, 56.6µM for HL-60, THP-1 and Caco2 cells, respectively. And compound 1 showed antibacterial activity toward Bacillus cereus (IC50=49µg/mL, IC90=111µg/mL) and Bacillus subtilis (IC50=10µg/mL, IC90=85µg/mL).

Comparison of local infiltration analgesia and sciatic nerve block as an adjunct to femoral nerve block for pain control after total knee arthroplasty: A systematic review and meta-analysis.

BACKGROUND: To perform a meta-analysis to assess the efficiency and safety between local infiltration analgesia (LIA) and sciatic nerve block (SNB) when combined with femoral nerve block (FNB) for pain control following total knee arthroplasty (TKA). METHODS: We systemically searched the following electronic databases for potentially relevant articles: Embase (1980-2017.01), Medline (1966-2017.01), PubMed (1966-2017.01), ScienceDirect (1985-2017.01), web of science (1950-2017.01) and the Cochrane Library. Only studies published in English that were accessible online were considered. Furthermore, we only considered studies that were published from 1966 to 2017. Only studies that met the following inclusion criteria were considered: (a) patients were adult human subjects who were set to undergo TKA; (b) the intervention was either SNB combined with FNB or LIA combined with FNB; (c) the outcomes of the studies, such as visual analog scale (VAS) scores, morphine consumption, length of stay and postoperative adverse effects, including the risk of nausea, vomiting and falls, were reported; (d) studies were either RCTs or non-RCT. Meta-analysis was performed using Stata 11.0 software. Modified Jadad score (7-points scale) which was based on Cochrane Handbook for Systematic Reviews of Interventions is used for assessment of RCTs. The Methodological Index for Nonrandomized Studies (MINORS) scale was used to assess non-RCTs with scores ranging 0 to 24. The synthesis of the outcomes for all studies was calculated as the weighted average rate by using a fixed or random effect model which depends on statistical heterogeneity. Systematic review registration number is CRD42017110661. RESULTS: Three randomized controlled trials (RCTs) and 2 nonrandomized controlled trials (Non-RCTs), including 240 patients met the inclusion criteria. The present meta-analysis indicated that there were significant differences between groups in terms of visual analog scale (VAS) score at 12 hours (SMD = -0.337, 95% CI: -0.593 to -0.081, P =.010), VAS score at 24 hours (SMD = -0.337, 95% CI: -0.612 to -0.061, P =.017), morphine equivalent consumption at 24 hours (SMD = -0.371, 95% CI: -0.627 to -0.114, P = .005) and incidence of nausea (RD = 0.215, 95% CI: 0.078 to 0.353, P = .002) and vomiting (RD = 0.143, 95% CI: 0.026 to 0.260, P = .017). CONCLUSION: FNB combined with SNB provided decreased VAS scores and less morphine consumption at 12 and 24 hours compared with FNB combined with LIA in total knee arthroplasty. In addition, it was associated with lower risks of nausea and vomiting. We assessed the quality of the evidence as low to very low; therefore, our confidence in the effect estimate is limited, and the true effect may be substantially different from our estimates. Further studies should focus on surgeries that are known to be associated with significant postoperative pain, particularly surgeries where improved pain control may deliver significant clinical benefits through reduced morbidity, or cost-effectiveness benefits through faster rehabilitation and discharge. The present meta-analysis has the following limitations: (1) only 5 studies were included in the meta-analysis. Although all of them are recently published studies, the sample sizes are relatively small; (2) Functional outcome is an important parameter; however, owing to the insufficiency of relevant data, we failed to perform a meta-analysis on functional outcome; (3) The doses of anesthetics and the concomitant pain management regimes varied between the studies, which may have influenced the results; (4) The duration of follow-up was relatively short, which might have led to an underestimating of complications; and (5) publication bias present in the meta-analysis may have influenced the results.

The anti-hepatic fibrosis effects of dihydrotanshinone I are mediated by disrupting the yes-associated protein and transcriptional enhancer factor D2 complex and stimulating autophagy.

BACKGROUND AND PURPOSE: Dihydrotanshinone I (DHI), a lipophilic component of traditional Chinese medicine Salvia miltiorrhiza Bunge, has various therapeutic effects. We investigated the anti-fibrotic effect of DHI and its underlying mechanisms in vitro and in vivo. EXPERIMENTAL APPROACH: Rats subjected to bile duct ligation (BDL) were treated with DHI (25 mg·kg-1 ·day-1 , i.p.) for 14 days. Serum biochemical and liver tissue morphological analyses were performed. The human hepatic stellate cell line LX-2 served as a liver fibrosis model in vitro. Liver fibrogenic genes, yes-associated protein (YAP) downstream genes and autophagy markers were examined using western blot and real-time PCR analyses. Similar analyses were done in rat primary hepatic stellate cells (pHSCs). Autophagy flux was assessed by immunofluorescence. KEY RESULTS: In BDL rats, DHI administration attenuated liver necrosis, bile duct proliferation and collagen accumulation and reduced the expression of genes associated with fibrogenesis, including Tgfb1, Mmp-2, Acta2 and Col1a1. DHI (1, 5, 10 µmol·L-1 ) time- and dose-dependently suppressed the protein level of COL1A1, TGFß1 and α-SMA in LX-2 cells and rat pHSCs. Furthermore, DHI blocked the nuclear translocation of YAP, which inhibited the YAP/TEAD2 interaction and its downstream fibrogenic genes, connective tissue growth factor, SOX4 and survivin. This stimulated autophagic flux and accelerated the degradation of liver collagen. CONCLUSIONS AND IMPLICATIONS: DHI exerts anti-fibrotic effects in BDL rats, LX-2 cells and rat pHSCs by inhibiting the YAP and TEAD2 complex and stimulating autophagy. These findings indicate that DHI may be a potential therapeutic for the treatment of liver fibrosis.

Study of Malformin C, a Fungal Source Cyclic Pentapeptide, as an Anti-Cancer Drug.

Malformin C, a fungal cyclic pentapeptide, has been claimed to have anti-cancer potential, but no in vivo study was available to substantiate this property. Therefore, we conducted in vitro and in vivo experiments to investigate its anti-cancer effects and toxicity. Our studies showed Malformin C inhibited Colon 38 and HCT 116 cell growth dose-dependently with an IC50 of 0.27±0.07µM and 0.18±0.023µM respectively. This inhibition was explicated by Malformin C's effect on G2/M arrest. Moreover, we observed up-regulated expression of phospho-histone H2A.X, p53, cleaved CASPASE 3 and LC3 after Malformin C treatment, while the apoptosis assay indicated an increased population of necrotic and late apoptotic cells. In vivo, the pathological study exhibited the acute toxicity of Malformin C at lethal dosage in BDF1 mice might be caused by an acute yet subtle inflammatory response, consistent with elevated IL-6 in the plasma cytokine assay. Further anti-tumor and toxicity experiments proved that 0.3mg/kg injected weekly was the best therapeutic dosage of Malformin C in Colon 38 xenografted BDF1 mice, whereas 0.1mg/kg every other day showed no effect with higher resistance, and 0.9mg/kg per week either led to fatal toxicity in seven-week old mice or displayed no advantage over 0.3mg/kg group in nine-week old mice. Overall, we conclude that Malformin C arrests Colon 38 cells in G2/M phase and induces multiple forms of cell death through necrosis, apoptosis and autophagy. Malformin C has potent cell growth inhibition activity, but the therapeutic index is too low to be an anti-cancer drug.

Ginkgolide B produced endophytic fungus (Fusarium oxysporum) isolated from Ginkgo biloba.

To screen the presence of ginkgolide B-producing endophytic fungi from the root bark of Ginkgo biloba, a total of 27 fungal isolates, belonging to 6 different genus, were isolated from the internal root bark of the plant Ginkgo biloba. The fungal isolates were fermented on solid media and their metabolites were analyzed by TLC. The obtained potential ginkgolides-producing fungus, the isolate SYP0056 which was identified as Fusarium oxysporum, was successively cultured in the liquid fermentation media, and its metabolite was analyzed by HPLC. The ginkgolide B was successfully isolated from the metabolite and identified by HPLC/ESI-MS and (13)C-NMR. The current research provides a new method to produce ginkgolide B by fungal fermentation, which could overcome the natural resource limitation of isolating from the leaves and barks of the plant Ginkgo biloba.

[Identification of foliumn pyrrosiae from different habitats and species by HPLC fingerprint].

OBJECTIVE: To establish HPLC fingerprint of Folium Pyrrosiae for identification. METHODS: The HPLC method was developed with Diamonsil C18 column (250 mm x 4.6 mm, 5 microm),and a mixture liquid of acetonitrile-0.8% acetic acid solution as mobile phase in a gradient elution. HPLC fingerprints of44 samples were analyzed by similarity, cluster and principal component analysis. RESULTS: The HPLC fingerprint common pattern of Pyrrosia petiolosa, Pyrrosia lingua and common pattern of Pyrrosia sheareri were set up separately. Samples from different species were classified based on the result of cluster and principal component analysis. Fingerprints of Pyrrosia sheareri and Pyrrosia lingua have high degree of similarity, but were different from Pyrrosia petiolosa, while Pyrrosia calvata and Pyrrosia assimlis were classified as adulterants with their dissimilar fingerprints. CONCLUSION: The method is stable and reliable with a good reproducibility and provides a reference standard for identifying Folium Pyrrosiae from different habitats and species.

Structural characterization and identification of biflavones in Selaginella tamariscina by liquid chromatography-diode-array detection/electrospray ionization tandem mass spectrometry.

Biflavonoids, a special class of flavonoids, are widely distributed in gymnosperm plants and have various biological activities. They are also major bioactive ingredients in Selaginella tamariscina. In this work, we report the use of high-performance liquid chromatography with a diode-array detector (HPLC-DAD) and electrospray ionization multi-stage tandem mass spectrometry (ESI-MS(n)) to study the fragmentation behavior of three main types of biflavonoids using seven biflavonoid reference compounds and analyze the biflavonoids in Selaginella tamariscina. The most useful fragmentations in terms of structural identification are those involving the C-ring cleavage of biflavonoids. For amentoflavone-type biflavonoids (containing flavonoid parts I and II), fragmentation on the flavonoid part II at positions 1/3 and 0/4 are the primary pathways, whereas the chances are greater for C-ring cleavage fragmentation occurring on flavonoid part I at positions 1/3 and 1/4 for robustaflavone-type biflavonoids. However, the predominant diagnostic ions of the specific C-O-C-connected hinokiflavone-type biflavonoids are a series of ions resulting from the rupture of the connective C-O bond. Based on the fragmentation patterns of these reference compounds, 17 biflavonoids were identified in an extract of Selaginella tamariscina, three of which have not been previously reported as constituents of this plant. This study provides a powerful approach for the online structural elucidation and identification of different types of biflavonoids and positional isomers from Selaginella tamariscina and other biflavonoids distributed in related plants and prescriptions.