Engineering cascade biocatalysis in whole cells for syringic acid bioproduction.

BACKGROUND: Syringic acid (SA) is a high-value natural compound with diverse biological activities and wide applications, commonly found in fruits, vegetables, and herbs. SA is primarily produced through chemical synthesis, nonetheless, these chemical methods have many drawbacks, such as considerable equipment requirements, harsh reaction conditions, expensive catalysts, and numerous by-products. Therefore, in this study, a novel biotransformation route for SA production was designed and developed by using engineered whole cells. RESULTS: An O-methyltransferase from Desulfuromonas acetoxidans (DesAOMT), which preferentially catalyzes a methyl transfer reaction on the meta-hydroxyl group of catechol analogues, was identified. The whole cells expressing DesAOMT can transform gallic acid (GA) into SA when S-adenosyl methionine (SAM) is used as a methyl donor. We constructed a multi-enzyme cascade reaction in Escherichia coli, containing an endogenous shikimate kinase (AroL) and a chorismate lyase (UbiC), along with a p-hydroxybenzoate hydroxylase mutant (PobA**) from Pseudomonas fluorescens, and DesAOMT; SA was biosynthesized from shikimic acid (SHA) by using whole cells catalysis. The metabolic system of chassis cells also affected the efficiency of SA biosynthesis, blocking the chorismate metabolism pathway improved SA production. When the supply of the cofactor NADPH was optimized, the titer of SA reached 133 µM (26.2 mg/L). CONCLUSION: Overall, we designed a multi-enzyme cascade in E. coli for SA biosynthesis by using resting or growing whole cells. This work identified an O-methyltransferase (DesAOMT), which can catalyze the methylation of GA to produce SA. The multi-enzyme cascade containing four enzymes expressed in an engineered E. coli for synthesizing of SA from SHA. The metabolic system of the strain and biotransformation conditions influenced catalytic efficiency. This study provides a new green route for SA biosynthesis.

Biosynthesis of D-1,2,4-butanetriol promoted by a glucose-xylose dual metabolic channel system in engineered Escherichia coli.

D-1,2,4-butanetriol (BT) is a widely used fine chemical that can be manufactured by engineered Escherichia coli expressing heterologous pathways and using xylose as a substrate. The current study developed a glucose-xylose dual metabolic channel system in an engineered E. coli and Combinatorially optimized it using multiple strategies to promote BT production. The carbon catabolite repression effects were alleviated by deleting the gene ptsG that encodes the major glucose transporter IICBGlc and mutating the gene crp that encodes the catabolite repressor protein, thereby allowing C-fluxes of both glucose and xylose into their respective metabolic channels separately and simultaneously, which increased BT production by 33% compared with that of the original MJ133K-1 strain. Then, the branch metabolic pathways of intermediates in the BT channel were investigated, the transaminase HisC, the ketoreductases DlD, OLD, and IlvC, and the aldolase MhpE and YfaU were identified as the enzymes for the branched metabolism of 2-keto-3-deoxy-xylonate, deletion of the gene hisC increased BT titer by 21.7%. Furthermore, the relationship between BT synthesis and the intracellular NADPH level was examined, and deletion of the gene pntAB that encodes a transhydrogenase resulted in an 18.1% increase in BT production. The combination of the above approaches to optimize the metabolic network increased BT production by 47.5%, resulting in 2.67 g/L BT in 24 deep-well plates. This study provides insights into the BT biosynthesis pathway and demonstrates effective strategies to increase BT production, which will promote the industrialization of the biosynthesis of BT.

Marine Natural Products as Novel Treatments for Parasitic Diseases.

Parasitic diseases including malaria, leishmaniasis, and trypanosomiasis have received significant attention due to their severe health implications, especially in developing countries. Marine natural products from a vast and diverse range of marine organisms such as sponges, corals, molluscs, and algae have been found to produce unique bioactive compounds that exhibit promising potent properties, including antiparasitic, anti-Plasmodial, anti-Leishmanial, and anti-Trypanosomal activities, providing hope for the development of effective treatments. Furthermore, various techniques and methodologies have been used to investigate the mechanisms of these antiparasitic compounds. Continued efforts in the discovery and development of marine natural products hold significant promise for the future of novel treatments against parasitic diseases.

Isolated medial patellofemoral ligament reconstruction improves static bipedal balance control in young patients with recurrent lateral patellar instability.

BACKGROUND: Knee stability can be safely and reliably restored using medial patellofemoral ligament (MPFL) reconstruction, which is widely recognized in patients with recurrent lateral patellar instability. However, the literature regarding its influence on static balance control is limited. Thus, this study aimed to assess the impact of MPFL reconstruction on balance control and determine its functional significance. METHODS: The study comprised 26 patients with recurrent lateral patellar instability, scheduled for MPFL reconstruction, and 26 matched healthy controls who underwent double-leg stance static posturographic tests pre- and postoperatively on a vertical force platform. Four test conditions were performed with their eyes open and closed, without and with foam support to evaluate the balance control of all participants. The International Knee Documentation Committee subjective knee form, Lysholm knee scoring scale, Tampa scale for kinesiophobia, and active range of motion of the affected knee were synchronously obtained and assessed. RESULTS: More postural sway was observed in patients compared to the healthy controls, 11 ± 5 days preoperatively (p < 0.01). However, 374 ± 23 days postoperatively, postural sway between the patients and control subjects was comparable (p > 0.05). Patients following MPFL reconstruction demonstrated better postural stability (p < 0.01). Significant ameliorations were found in all clinical assessments in the study patients postoperatively (p < 0.01). CONCLUSIONS: Patients with recurrent lateral patellar instability have inefficient balance control. Static bipedal balance control can be improved under surface perturbation in these patients one year after isolated MPFL reconstruction that enhances the possibility of normal restoration of postural stability. Structural recovery of the ligament could help restore the sensorimotor efficiency and generate the compensatory and anticipatory balance regulation strategies, thereby improving joint function.

UR-Net: An Integrated ResUNet and Attention Based Image Enhancement and Classification Network for Stain-Free White Blood Cells.

The differential count of white blood cells (WBCs) can effectively provide disease information for patients. Existing stained microscopic WBC classification usually requires complex sample-preparation steps, and is easily affected by external conditions such as illumination. In contrast, the inconspicuous nuclei of stain-free WBCs also bring great challenges to WBC classification. As such, image enhancement, as one of the preprocessing methods of image classification, is essential in improving the image qualities of stain-free WBCs. However, traditional or existing convolutional neural network (CNN)-based image enhancement techniques are typically designed as standalone modules aimed at improving the perceptual quality of humans, without considering their impact on advanced computer vision tasks of classification. Therefore, this work proposes a novel model, UR-Net, which consists of an image enhancement network framed by ResUNet with an attention mechanism and a ResNet classification network. The enhancement model is integrated into the classification model for joint training to improve the classification performance for stain-free WBCs. The experimental results demonstrate that compared to the models without image enhancement and previous enhancement and classification models, our proposed model achieved a best classification performance of 83.34% on our stain-free WBC dataset.

Optimization of multi-enzyme cascade process for the biosynthesis of benzylamine.

Benzylamine is a valuable intermediate in the synthesis of organic compounds such as curing agents and antifungal drugs. To improve the efficiency of benzylamine biosynthesis, we identified the enzymes involved in the multi-enzyme cascade, regulated the expression strength by using RBS engineering in Escherichia coli, and established a regeneration-recycling system for alanine. This is a cosubstrate, coupled to cascade reactions, which resulted in E. coli RARE-TP and can synthesize benzylamine using phenylalanine as a precursor. By optimizing the supply of cosubstrates alanine and ammonia, the yield of benzylamine produced by whole-cell catalysis was increased by 1.5-fold and 2.7-fold, respectively, and the final concentration reached 6.21 mM. In conclusion, we achieved conversion from l-phenylalanine to benzylamine and increased the yield through enzyme screening, expression regulation, and whole-cell catalytic system optimization. This demonstrated a green and sustainable benzylamine synthesis method, which provides a reference and additional information for benzylamine biosynthesis research.

Dietary bile acid supplementation in weaned piglets with intrauterine growth retardation improves colonic microbiota, metabolic activity, and epithelial function.

BACKGROUND: Intrauterine growth retardation (IUGR) is one of the major constraints in animal production. Our previous study showed that piglets with IUGR are associated with abnormal bile acid (BA) metabolism. This study explored whether dietary BA supplementation could improve growth performance and colonic development, function, microbiota, and metabolites in the normal birth weight (NBW) and IUGR piglets. A total of 48 weaned piglets (24 IUGR and 24 NBW) were allocated to four groups (12 piglets per group): (i) NBW group, (ii) NBW + BA group, (iii) IUGR group, and (iv) IUGR + BA group. Samples were collected after 28 days of feeding. RESULTS: The results showed that dietary BA supplementation increased the length and weight of the colon and colon weight to body weight ratio, while decreased the plasma diamine oxidase (DAO) concentration in the NBW piglets (P < 0.05). Dietary BA supplementation to IUGR piglets decreased (P < 0.05) the plasma concentrations of D-lactate and endotoxin and colonic DAO and endotoxin, suggesting a beneficial effect on epithelial integrity. Moreover, dietary BA supplementation to NBW and IUGR piglets increased Firmicutes abundance and decreased Bacteroidetes abundance (P < 0.05), whereas Lactobacillus was the dominant genus in the colon. Metabolome analysis revealed 65 and 51 differential metabolites in the colon of piglets fed a diet with/without BA, respectively, which was associated with the colonic function of IUGR piglets. Furthermore, dietary BA supplementation to IUGR piglets upregulated the expressions of CAT, GPX, SOD, Nrf1, IL-2, and IFN-γ in colonic mucosa (P < 0.05). CONCLUSIONS: Collectively, dietary BA supplementation could improve the colonic function of IUGR piglets, which was associated with increasing proportions of potentially beneficial bacteria and metabolites. Furthermore, BA shows a promising application prospect in improving the intestinal ecosystem and health of animals.

Obesity impacts placental function through activation of p-IRE1a-XBP1s signaling.

Maternal obesity is associated with a variety of obstetrical outcomes including stillbirth, preeclampsia, and gestational diabetes, and increases the risk of fetuses for congenital heart defects. Obesity during pregnancy represents a major contribution to metabolic dysregulation, which not only plays a key role in the pathogenesis of adverse outcome but also can potently induce endoplasmic reticulum (ER) stress. However, the mechanism associating such an obesogenic metabolic environment and adverse pregnancy outcomes has remained poorly understood. In this study, we aimed to determine whether the ER stress pathways (also named unfolded protein response (UPR)) were activated in the placenta by obesity. We collected placenta from the obese pregnancy (n = 12) and non-obese pregnancy (n = 12) following delivery by Caesarean-section at term. The specimens were assessed with immunocytochemistry staining and RT-QPCR. Our results revealed that in the obese placenta, p-IRE1α and XBP1s were significantly increased, CHOP and nine UPR chaperone genes were upregulated, including GRP95, PDIA6, Calnexin, p58IPK, SIL-1, EDEM, Herp, GRP58 and Calreticulin. However, Perk and BiP are not activated in the obese placenta. Our data suggest that upregulated p-IRE1α and XBP1s signaling, and UPR chaperone genes may play an important role in maternal obesity-induced placental pathology. In conclusion, this is the first report on ER stress and UPR activation in the placenta of maternal obesity. Our findings represent the first step in the understanding of one of the key ER signaling pathways, also referred to IRE1α-XBP1, in placental pathophysiology affected by obesity, which may be an important mechanism accounting for the observed higher maternal and perinatal risks.

Suppressive effect of pseudolaric acid B on Echinococcus multilocularis involving regulation of TGF-ß1 signaling in vitro and in vivo.

Echinococcus multilocularis, the causative agent of alveolar echinococcosis (AE), severely threats human health and livestock farming. The first line of chemotherapeutic drug for AE is albendazole, which limits rapid extension of E. multilocularis metacestodes, but is rarely curative for AE, with severe side effects in long-term use, thus development of new anti-echinococcal drugs is mandated. Pseudolaric acid B (PAB) has long been used to treat fungal-infected dermatosis, and exerted anti-tumor, -fertility, -angiogenesis, -tubulin and antiparasitic activity. However, the effect of PAB against Echinococcus spp. remains unclear. The present study is to understand the effect of PAB against E. multilocularis in vitro and in vivo, and identify potential anti-echinococcal mechanism, as well as its toxicity. After exposure to PAB at 20 µg/ml, significant reduction of the survival rate and substantial ultrastructural destructions in E. multilocularis protoscoleces were observed in vitro. Furthermore, the wet weight of E. multilocularis cysts in the infected mice was significantly decreased after treatment with PAB (40, 20 or 10 mg/kg) for 12 weeks. Meanwhile, significant increase of both protein and mRNA expression of transforming growth factor beta 1 (TGF-ß1) was detected in the serum and liver of the infected mice, whereas PAB administration lowered its expression significantly. The toxicity tests demonstrated that PAB displayed lower cytotoxicity to human liver and kidney cells (HL-7702 and HK-2 cell) with IC50 = 25.29 and 42.94 µg/ml than albendazole with IC50 = 3.71 and 21.22 µg/ml in vitro, and caused lower hepatoxicity and nephrotoxicity in mice than ABZ. Our findings indicated that PAB possesses potent anti-echinococcal effect, with lower toxicity than albendazole, implying a potential chemotherapeutic agent for AE. Additionally, the present study demonstrated that the suppressive effect of PAB on the parasite may involve down-regulation of TGF-ß1 signaling.

Anticancer effects of OSW-1 on glioma cells via regulation of the PI3K/AKT signal pathway: A network pharmacology approach and experimental validation in vitro and in vivo.

Background: Gliomas are the most common primary intracranial malignant tumors with poor prognosis, despite the remarkable advances in medical technology that have been made. OSW-1, isolated from Ornithogalum saundersiae, possesses anticancer activity against various malignant cancer cells. However, the effects of OSW-1 on gliomas and its potential mechanisms remain unclear. Methods: Network pharmacology was employed for predicting potential key targets and mechanisms of the anticancer effects of OSW-1 on glioma. Experiments, including the Cell Counting Kit-8, colony formation, and flow cytometry, were performed to investigate how OSW-1 affects the biological behavior of glioma cells in vitro. Western blotting was used to detect changes in related proteins, such as those involved in the cell cycle, apoptosis, and signaling pathways. The nude mouse xenograft model was used to detect the effect of OSW-1 on inhibiting the proliferation of glioma cells in vivo. Results: An "OSW-1-Targets-Glioma" intersection network consisting of 151 intersecting genes was acquired to construct a "Protein-Protein Interaction network" and predict the top 10 core targets. According to the Kyoto Encyclopedia of Genes and Genomes pathway analysis, the PI3K/AKT signaling pathway was the top 3-ranked pathway, with 38 enriched intersecting genes. The glioma T98G and LN18 cell lines were used to verify the predictions. OSW-1 significantly inhibited the viability and proliferation of glioma cells in a dose- and time-dependent manner. Flow cytometry showed that OSW-1 arrested the cell cycle at the G2/M phase, and the apoptotic ratio of glioma cells increased significantly with increasing concentrations. Western blotting revealed that the expression levels of p-PI3K and p-AKT1 in glioma cells treated with OSW-1 were significantly lower than those in the controls; however, 740Y-P, a PI3K activator, significantly reversed the inactivation of the PI3K/AKT signaling pathway caused by OSW-1. Furthermore, the mouse xenograft model confirmed the suppressive effect of OSW-1 on tumor growth in vivo. Conclusion: OSW-1 is a promising anti-glioma chemotherapeutic drug owing to its anticancer effects via downregulation of the PI3K/AKT signaling pathway. However, OSW-1 still has a long way to go to become a real anti-glioma drug.

Berberine inhibits glioma cell migration and invasion by suppressing TGF-ß1/COL11A1 pathway.

Glioma is a clinically heterogeneous disease with a poor prognosis. Berberine (BBR), as a multi-target anti-tumor alkaloid, has the ability to penetrate the blood-brain barrier and shows cytotoxicity to glioma cells. In previous studies, we demonstrated that berberine inhibits glioma cell proliferation by inhibiting mutant p53 protein and promoting mitochondrial damage. In addition, berberine has been shown to reduce collagen accumulation in pulmonary fibrosis, diabetic nephropathy and arthritis. However, its effect on collagen in cancer needs to be further elucidated. In this study, we proved that the collagen XI alpha 1 chain (COL11A1) is highly expressed in glioma cell lines and associated with migration and invasion of glioma cells. Knocking down COL11A1 caused decreased expression of MMPs. Berberine could inhibit the migration and invasion of glioma cells by suppressing the TGF-ß1/COL11A1 pathway and changes actin cytoskeleton arrangement. Nude mouse subcutaneous xenografts model also showed that berberine inhibited the expression of COL11A1 in vivo. Collectively, berberine that targets COL11A1 to inhibit glioma migration and invasion, may serve as a promising candidate for the development of anti-glioma drugs in the future.

Performance Improvement of NIR Spectral Pattern Recognition from Three Compensation Models' Voting and Multi-Modal Fusion.

Inspired by aquaphotomics, the optical path length of measurement was regarded as a perturbation factor. Near-infrared (NIR) spectroscopy with multi-measurement modals was applied to the discriminant analysis of three categories of drinking water. Moving window-k nearest neighbor (MW-kNN) and Norris derivative filter were used for modeling and optimization. Drawing on the idea of game theory, the strategy for two-category priority compensation and three-model voting with multi-modal fusion was proposed. Moving window correlation coefficient (MWCC), inter-category and intra-category MWCC spectra, and k-shortest distances plotting with MW-kNN were proposed to evaluate weak differences between two spectral populations. For three measurement modals (1 mm, 4 mm, and 10 mm), the optimal MW-kNN models, and two-category priority compensation models were determined. The joint models for three compensation models' voting were established. Comprehensive discrimination effects of joint models were better than their sub-models; multi-modal fusion was better than single-modal fusion. The best joint model was the dual-modal fusion of compensation models of one- and two-category priority (1 mm), one- and three-category priority (10 mm), and two- and three-category priority (1 mm), validation's total recognition accuracy rate reached 95.5%. It fused long-wave models (1 mm, containing 1450 nm) and short-wave models (10 mm, containing 974 nm). The results showed that compensation models' voting and multi-modal fusion can effectively improve the performance of NIR spectral pattern recognition.

Antitumor Effect of Pseudolaric Acid B Involving Regulation of Notch1/Akt Signaling Response in Human Hepatoma Cell In Vitro.

Background: Liver cancer, particularly hepatocellular carcinoma (HCC), is the fourth leading cause of cancer-related death worldwide. Sorafenib is a crucial drug for the treatment of advanced HCC, but it is difficult to meet the challenge of increasing clinical demands due to its severe side effects and drug resistance. Hence, development of novel antitumor drugs is urged. Previous studies showed that pseudolaric acid B (PAB) could reduce the expression of protein kinase B (PKB/Akt), a downstream effector of Notch signaling, facilitating cell apoptosis in HCC. The disruption of Notch signaling was verified to exacerbate malignant progression and drug resistance, however, the antitumor effect of PAB on Notch signaling in HCC remains unclear. Thus, this study aims to investigate the anti-HCC effect of PAB in association with the regulation of Notch1/Akt signaling. Methods: CCK-8 assay and transwell assay were used to examine the cell proliferation and invasion in Huh7 cells after treatment with PAB and a Notch inhibitor DAPT. Moreover, the cell cycle of Huh7 cells after treatment with PAB was analyzed using flow cytometry. Finally, the changes of Notch1, Jagged1, Hes1, and Akt expression at the protein and mRNA level in Notch1/Akt signaling in Huh7 cells after treatment with PAB and DAPT were analyzed using immunofluorescence assay and real-time qPCR. Results: The proliferation rate of Huh7 cells exposed to PAB of 0.5, 1, 2, 4, 8, 10, 20, 40, 80, 100, and 200 µmol/L revealed a time-and dose-dependent decrease in vitro, showing cell cycle arrest at G2/M phase (P < 0.05). Furthermore, compared with the untreated group, at the concentration of 40 µmol/L, the proliferation rate and invasion rate of Huh7 cells in PAB, DAPT, and PAB-DAPT combination (PAB + DAPT) group were significantly decreased (P < 0.05), but the PAB + DAPT showed no synergistic antiproliferation and anti-invasion effect in comparison with PAB treatment alone (P > 0.05). In addition, compared with the untreated group, PAB and DAPT alone significantly downregulated the expression of Notch1, Jagged1, Hes1, Akt mRNA, or/and protein in Huh7 cells (P < 0.05), but there was no significant difference in synergistic downregulated effect between the PAB + DAPT group and the PAB group (P > 0.05). Conclusion: PAB can suppress proliferation and invasion of HCC cells through downregulating the expression of Notch1/Akt signaling protein and mRNA, and may be a potential novel antitumor drug candidate for the clinical treatment of HCC in the future.

AMPK Signaling Regulates Mitophagy and Mitochondrial ATP Production in Human Trophoblast Cell Line BeWo.

INTRODUCTION: Accumulating evidence suggests that mitochondrial structural and functional defects are present in human placentas affected by pregnancy related disorders, but mitophagy pathways in human trophoblast cells/placental tissues have not been investigated. METHODS: In this study, we investigated three major mitophagy pathways mediated by PRKN, FUNDC1, and BNIP3/BNIP3L in response to AMPK activation by AICAR and knockdown of PRKAA1/2 (AKD) in human trophoblast cell line BeWo and the effect of AKD on mitochondrial membrane potential and ATP production. RESULTS: Autophagy flux assay demonstrated that AMPK signaling activation stimulates autophagy, evidenced increased LC3II and SQSTM1 protein abundance in the whole cell lysates and mitochondrial fractions, and mitophagy flux assay demonstrated that the activation of AMPK signaling stimulates mitophagy via PRKN and FUNDC1 mediated but not BNIP3/BNIP3L mediated pathways. The stimulatory regulation of AMPK signaling on mitophagy was confirmed by AKD which reduced the abundance of LC3II, SQSTM1, PRKN, and FUNDC1 proteins, but increased the abundance of BNIP3/BNIP3L proteins. Coincidently, AKD resulted in elevated mitochondrial membrane potential and reduced mitochondrial ATP production, compared to control BeWo cells. CONCLUSIONS: In summary, AMPK signaling stimulates mitophagy in human trophoblast cells via PRKN and FUNDC1 mediated mitophagy pathways and AMPK regulated mitophagy contributes to the maintenance of mitochondrial membrane potential and mitochondrial ATP production.

Investigating the origin of the fetal gut and placenta microbiome in twins.

OBJECTIVE: It is widely accepted that the microbiota is critical for human well-being; however, the origin of microbiota in the newborn is not well understood. In this study, we hypothesized that within a maternal-twin dyad (MTD) the meconium microbiome will be similar to the placenta microbiome and the meconium microbiome of within MTD will be similar to one another. METHODS: Prospectively, meconium (proxy for fetal gut), placenta and maternal buccal, skin, vaginal, stool samples were collected from a cohort of MTDs at time of delivery hospitalization. We performed gene sequencing using the V4 region of 16S rRNA with rigorous negative controls. Alpha and beta diversity indices were computed to characterize the microbial community of MTD samples. A p value of <.05 was considered significant. RESULTS: From 17 MTD, 87/132 samples were successfully sequenced. The alpha diversity of the microbiome collected from all the body sites were different (p ≤ .001). The meconium samples when compared to other samples in the MTD microbial community were different (p = .009) and the Bray-Curtis dissimilarity was greater than 0.95 for all of the comparisons (beta diversity). The MTD within-twin placenta microbiome samples were also different, confirmed by Bray-Curtis pairwise dissimilarity distance, 0.83. CONCLUSION: The fetal gut microbiome is different from placenta and maternal buccal, skin, vaginal and stool microbiome. We clearly identified a distinct placenta microbiome. Furthermore, placentas in the same MTD have distinct microbiomes, suggesting that fetal gut and placenta origin is complex and remains unclear.

Uterine artery embolization, surgery and high intensity focused ultrasound in the treatment of uterine fibroids: a network meta-analysis.

BACKGROUND: To systematic review the safety and effectiveness between uterine artery embolization (UAE), surgery and high intensity focused ultrasound (HIFU) in the treatment of uterine fibroids. METHODS: The PubMed, EMbase, The Cochrane Library, Web of Science, Wanfang Data, and CNKI were electronically searched to collect relevant studies on comparing the safety and effectiveness of UAE, surgery and HIFU in the treatment of uterine fibroids from January 2000 to August 2019. After two reviewers independently screened the literature, extracted the data and evaluated the risk of bias of included studies, network meta-analysis was performed by ADDIS 1.16.8 and Stata 14 software. RESULTS: A total of 11 studies (22 articles) involving 3,646 patients were included. Compared with surgery, UAE and HIFU patients had higher quality of life (1-year follow-up) improvement, and UAE was higher than HIFU. Network meta-analysis show that patients treated with HIFU had the lowest incidence of major complications within 1 year, followed by UAE, and the highest surgery. Patients treated with HIFU and UAE have shorter hospital stays and quicker recovery time than surgery. The rate of further intervention after surgery treatment might be lower than that of UAE and HIFU. CONCLUSIONS: UAE has the highest quality of life improvement (1-year follow-up) for uterine fibroids. HIFU and UAE are safer with shorter hospital stays and quicker recovery time compared with surgery. However, both UAE and HIFU have the risks of re-treatment. However, limited by the number and quality of included studies, the above conclusions need to be verified through more high-quality studies.

Mechanisms involved in the anti-tumor effects of Toosendanin in glioma cells.

BACKGROUND: Toosendanin (TSN) is a triterpenoid compound mainly used as an ascaris repellant. Recent studies have shown that it possesses antitumor effects in many types of tumor cells. However, the effects of TSN on glioma cells have rarely been reported. METHODS: Different assays were performed to investigate the effects of TSN on the different glioma cell lines including U87MG and LN18. The assays included colony formation, wound healing, and transwell assays. Furthermore, Hoechst 33342 staining, flow cytometry, and western blotting analysis were performed to investigate the apoptotic activities of TSN. Finally, the results were confirmed using a xenograft tumor model that comprised of nude mice. RESULTS: In vitro, the CCK-8 and colony formation assays showed that TSN effectively inhibited glioma cell proliferation. Moreover, the inhibitory effects on glioma cell migration and invasion were demonstrated through the wound healing and transwell assays, respectively. Hoechst 33342 staining, flow cytometry, and western blotting assays demonstrated the significant effect of TSN in the apoptosis induction of glioma cells. Furthermore, the anti-glioma effect of TSN was exerted through the inhibition of the PI3K/Akt/mTOR signaling pathways as demonstrated by western blotting analysis. In addition, the effects of TSN on glioma cell viability, apoptosis, cell cycle arrest, migration, and invasion were reversed by 740Y-P, a PI3K activator. Finally, the mouse xenograft model confirmed the suppressive effect of TSN on tumor growth in vivo. CONCLUSION: Our results suggest that TSN is a promising chemotherapeutic drug for patients with glioma.

Research on the efficient water-absorbing ceramsite generated by dredged sediments in Dian Lake-China and coal fly ash.

In order to transform the dredged sediment (DS) into an efficient water-absorbing ceramsite (EWAC), the coal fly ash (CFA) and expansion agent were used to blend, expand, and sinter with the DS in the Dian Lake-China. A new type of high EWAC was prepared with the absorption ratio of 66.71%, which was much higher than similar products. The heavy metals leaching (HML) of EWAC showed that the concentration of As was 0.90 mg/L and the Hg, Pb, Cd, and Cr were too low to be detected. The characterization analysis showed that the EWAC cross section contained a lot of hydroxyl, ether, and P-Cl hydrophilic group by Fourier transform infrared (FT-IR), scanning electron microscope (SEM), and Brunauer-Emmett-Teller (BET) specific surface area (SSA) test method. The above groups and structures could greatly improve the water absorption (WA) performance of the EWAC. What's more, the SSA of the EWAC could reach 4.468 m2 /g. The results of Comsol Multiphysics indicated that the SSA and average pore size (APS) of the EWACs were 10 and 6 times higher than the commercial ceramsites, respectively. The research provided the utilization of the DS with technical and theoretical basis for the construction of sponge city. PRACTITIONER POINTS: The article was focus on the utilization of dredged sediment (DS) and coal fly ash (CFA) for the basic material preparation technology and its toxicity test as the sponge city. First, the raw materials were the DS in Dian Lake (Kunming, Yunnan, China) and CFA (thermal power plants), which were all belonged to the hazardous solid waste and was made to the efficient water-absorbing ceramsite (EWAC). Second, the water absorption (WA) performance of the EWAC was improved greatly whose absorption ratio was much higher than similar products reached 66.71%. The specific surface area (SSA) and average pore size (APS) of the EWACs were 10 and 6 times higher than the commercial ceramsites (CCs), respectively. Finally, the heavy metals leaching (HML) of As was 0.90 mg/L, and the HML of Hg, Pb, Cd, and Cr was all lower than 0.05 mg/L, which could not only not cause secondary pollution but provide the new ideas for the resource utilization of large amount of DS. So, we thought this article was suitable for the journal.

Brucine inhibits proliferation of glioblastoma cells by targeting the G-quadruplexes in the c-Myb promoter.

The proto-oncogene c-Myb plays an important role in cell proliferation, and its upregulation affects the development of glioblastomas. G-quadruplexes are secondary DNA or RNA structures that usually form in the promoter region of oncogenes, including c-Myb, and regulate the expression of these genes. The traditional Chinese medicine, brucine, is a ligand of the G-quadruplexes located in the promoter region of c-Myb. The present study investigated the therapeutic effects and mechanism of action of brucine in U87, LN18, and LN229 cells in vitro and in vivo. Our results showed that brucine suppressed the growth of these cells in vitro by arresting the cell cycle and reducing c-Myb expression. Dual-luciferase reporter assays showed that brucine inhibited c-Myb expression by targeting the guanine-rich sequence that forms G-quadruplexes in the c-Myb promoter. Moreover, U87 tumors were suppressed by brucine in a tumor xenograft nude mouse model. Therefore, brucine is potentially effective for treating glioblastomas.

Pterostilbene promotes mitochondrial apoptosis and inhibits proliferation in glioma cells.

Glioma is the most general primary and lethal intracranial malignant tumor. Pterostilbene (PTE), an analog of stilbene and resveratrol, has attracted attention in recent years due to its significant antitumor activity in multiple solid tumors; however, its effect on drug-resistant glioma cells and the underlying mechanism have not yet been reported. In this study, we found that pterostilbene inhibited proliferation, induced intrinsic mitochondria-mediated apoptosis and caused S phase arrest, inhibited migration and excessive invasion in glioma cells. Pretreatment with the pan-caspase-inhibitor Z-VAD-FMK attenuated the PTE-induced apoptosis of glioma cells. Moreover, PTE significantly increased the production of reactive oxygen species (ROS) and reduce the mitochondrial membrane potential (MMP). Inhibition of ROS with N-acetyl-L-cysteine not only rescued PTE-induced reduction of cellular viability but also prevented glioma cell apoptosis. We also discovered ERK 1/2 and JNK signaling pathways were activated by PTE and contributed to induce glioma cell apoptosis. In addition, specific inhibitors of ERK 1/2 and JNK attenuated PTE-induced apoptosis. Besides, PTE significantly reduced tumor volume and prolonged median survival of tumor-bearing rats in vivo. In summary, the results of this study indicate that the anti-tumor effect of PTE on glioma cells may provide a new treatment option for glioma patients.