Hormone and reproductive factors and risk of systemic lupus erythematosus: a Mendelian randomized study.

Systemic lupus erythematosus (SLE) is an autoimmune and inflammatory disease with a risk associated with hormonal and reproductive factors. However, the potential causal effects between these factors and SLE remain unclear. A two-sample Mendelian randomization study was conducted using the published summary data from the genome-wide association study database. Five independent genetic variants associated with hormonal and reproductive factors were selected as instrumental variables: age at menarche, age at natural menopause, estradiol, testosterone, and follistatin. To estimate the causal relationship between these exposure factors and disease outcome, we employed the inverse-variance weighted, weighted median, and MR-Egger methods. In addition, we carried out multiple sensitivity analyses to validate model assumptions. Inverse variance weighted showed that there was a causal association between circulating follistatin and SLE risk (OR = 1.38, 95% CI 1.03 to 1.86, P = 0.033). However, no evidence was found that correlation between AAM (OR = 1.04, 95% CI 0.77 to 1.40, P = 0.798), ANM (OR = 0.99, 95% CI 0.92 to 1.06, P = 0.721), E2 (OR = 1.40, 95% CI 0.14 to 13.56, P = 0.772), T (OR = 1.25, 95% CI 0.70 to 2.28, P = 0.459), and SLE risk. Our study revealed that elevated circulating follistatin associates with an increased risk of SLE. This finding suggests that the regulatory signals mediated by circulating follistatin may provide a potential mechanism relevant to the treatment of SLE.

Facile Synthesis of Nd2Fe14B Hard Magnetic Particles with Microwave-Assisted Hydrothermal Method.

The synthesis of Nd-Fe-B magnetic powders via chemical techniques presents significant promise, but poses challenges due to their inherent chemical instability. In this investigation, Nd-Fe-B hard magnetic particles were synthesized utilizing an eco-friendly and simple microwave-assisted hydrothermal synthetic method. The technique involves the synthesis of the Nd-Fe-B oxide precursor using the microwave-assisted hydrothermal method, followed by reduction-diffusion using CaH2. The microwave-assisted hydrothermal technique presents a viable approach for preparing Nd-Fe-B precursor particles, offering advantages such as time and energy efficiency and environmental sustainability. The synthesized Nd-Fe-B particles demonstrated a coercivity of up to 2.3 kOe. These magnetic particles hold significant potential for use in high-performance permanent magnets, and can effectively contribute to developing high-energy density exchange-coupled nanocomposite magnets. This study also offers valuable insights into the design and synthesis of additional magnetic materials based on rare earth elements.

Direct and efficient conversion of cellulose to levulinic acid catalyzed by carbon foam-supported heteropolyacid with Brønsted-Lewis dual-acidic sites.

This study aimed to produce bio-based levulinic acid (LA) via direct and efficient conversion of cellulose catalyzed by a sustainable solid acid. A carbon foam (CF)-supported aluminotungstic acid (HAlW/CF) catalyst with Brønsted-Lewis dual-acidic sites was creatively engineered by a hydrothermal impregnation method. The activity of the HAlW/CF catalyst was determined via the hydrolysis and conversion of cellulose to prepare LA in aqueous system. The cooperative effect of Brønsted and Lewis acids in HAlW/CF resulted in high cellulose conversion (89.4%) and LA yield (60.9%) at 180 °C for 4 h, which were greater than the combined catalytic efficiencies of single HAlW and CF under the same conditions. The HAlW/CF catalyst in block form exhibited superior catalytic activity, facile separation from reaction system, and favorable reusability. This work offers novel perspectives for the development of recyclable dual-acidic catalysts to achieve one-pot catalytic conversion of biomass to value-added chemicals.

Lipidomics analysis facilitate insight into the molecular mechanisms of urate nephropathy in a gout model induced by combination of MSU crystals injection and high-fat diet feeding.

Renal injury is one of the most common clinical manifestations of patients with hyperuricaemia/gout. The precise pathophysiological mechanism(s) for the renal injury is still unknown. Furthermore, it is also unclear whether the clinical therapies (e.g., colchicine and febuxostat) could prevent its progression or not. Lipids are involved in almost all of important biological processes and play critical roles in maintaining the renal functions. Herein, shotgun lipidomics was performed for class-targeted lipid analysis of cellular lipidomes in renal tissue of a gouty model induced by combination of monosodium urate crystals injection and high-fat diet feeding with/without treatment with either colchicine or febuxostat. Serum uric acid (UA), proinflammatory cytokines (i.e., TNF-α and IL-6), xanthine oxidase activity, footpad swelling, and pain threshold were determined to evaluate the gouty severity. Renal histopathological changes, blood urea nitrogen, creatinine, and kidney index were used to reflect renal injury. Lipidomics analysis revealed that altered triacylglycerol (TAG) profile, impaired mitochondrial function resulted by decreased tetra 18:2 cardiolipin, reduced 4-hydroxyalkenal (HNE) species, and elevated lysophospholipids were already present in the kidneys at early stage of renal injury, probably contributing to its occurrence and development. In addition to significantly reduce the UA level and relief the gouty severity, treatment with either colchicine or febuxostat could restore HNE bioavailability, thereby delaying the progression of renal injury. However, both of them could not recover the altered TAG profile and the impaired mitochondrial function, indicating that treatment with either of them could not completely prevent the development of renal injury in the gouty model.

Construction of an evaluation system for medical staff's occupational protection ability based on knowledge, attitude, and practice theory, and a cross-sectional survey of current conditions.

INTRODUCTION: Medical personnel should be in close proximity and high frequency of contact with patients, and be exposed to physical, biological and chemical risk factors for a long time. The incidence of various occupational exposures is high. however, there is still a lack of the medical staff Occupational Protection Core Competence Evaluation Index system with high reliability and validity. AIM: Based on the theory of knowledge, attitude, and practice, the evaluation system of occupational protection ability of medical personnel was established, and the current situation of occupational protection ability of medical personnel at different levels was investigated, so as to take targeted training and intervention measures to improve the occupational protection ability of medical personnel and reduce the incidence of occupational exposure. METHODS: Based on the knowledge, attitude, and practice theory, the index system of occupational protection core competence of medical personnel was initially constructed by literature retrieval, expert consultation, group discussion, semi-structured interview and other qualitative and quantitative methods, and the reliability and validity of the index system was tested by Delphi expert consultation method. By convenient cluster sampling method, from March to September 2021, the current status of occupational protection core competence of medical personnel was investigated among medical staff from one Class III Grade A hospital and two medical schools in Jinan City, Shandong Province, China. RESULTS: The evaluation system for medical staff's occupational protection ability included 3 first-level indexes, 11 second-level indexes, and 109 third-level indexes. A total of 684 valid questionnaires were collected from Grade III, Class A hospital medical staff and two medical school students in clinical practice in Shandong, China. Kruskal Walls test showed that there were significant differences in the overall distribution of occupational protection knowledge, attitude, and practice among registered nurses, nursing students, registered physicians, and physician students (H = 70.252, P < 0.001; H = 76.507, P < 0.001; H = 80.782, P < 0.001); there were statistical significance in the knowledge/ attitude/ practice of nursing and physician students at different levels (H = 33.733, P < 0.001; H = 29.158, P < 0.001; H = 28.740, P < 0.001). CONCLUSION: The results of the evaluation system for the medical staff's occupational protection ability are reliable and can provide a reference for training the medical staff's occupational protection ability. Managers should strengthen the training of theoretical knowledge of occupational protection ability of medical staff.

Integrated gut microbiota and serum metabolomics reveal the protective effect of oleanolic acid on liver and kidney-injured rats induced by Euphorbia pekinensis.

Euphorbia pekinensis (EP) is a commonly used Chinese medicine treating edema with potential hepatorenal toxicity. However, its toxic mechanism and prevention are remained to be explored. Oleanolic acid (OA) is a triterpene acid with potential hepatorenal protective activities. We investigated the protective effect and potential mechanism of OA on EP-induced hepatorenal toxicity. In this study, rats were given total diterpenes from EP (TDEP, 16 mg/kg) combined with OA (10, 20, 40 mg/kg) by gavage for 4 weeks. The results showed that TDEP administration could lead to a 3-4-fold increasement in hepatorenal biochemical parameters with histopathological injuries, while OA treatment could ameliorate them in a dose-dependent manner. At microbial and metabolic levels, intestinal flora and host metabolism were perturbed after TDEP administration. The disturbance of bile acid metabolism was the most significant metabolic pathway, with secondary bile acids increasing while conjugated bile acids decreased. OA treatment can improve the disorder of intestinal flora and metabolic bile acid spectrum. Further correlation analysis screened out that Escherichia-Shigella, Phascolarctobacterium, Acetatifactor, and Akkermansia were closely related to the bile acid metabolic disorder. In conclusion, oleanolic acid could prevent hepatorenal toxicity induced by EP by regulating bile acids metabolic disorder via intestinal flora improvement.

High performance enhancement-mode thin-film transistor with graphene quantum dot-decorated In2O3 channel layers.

Due to the quantum confinement and edge effects, there has been ongoing enthusiasm to provide deep insight into graphene quantum dots (GQDs), serving as attractive semiconductor materials. To demonstrate the potential applications of GQDs in electronic devices, this work presents solution-processed high performance GQD-decorated In2O3 thin-film transistors (TFTs) based on ZrO2 as gate dielectrics. GQDs-In2O3/ZrO2 TFTs with optimized doping content have demonstrated high electrical performance and low operating voltage, including a larger field-effect mobility (µ FE) of 34.02 cm2 V-1 s-1, a higher I on/I off of 4.55 × 107, a smaller subthreshold swing (SS) of 0.08 V dec-1, a lower interfacial trap states (D it) of 5.84 × 1011 cm-2 and threshold voltage shift of 0.07 V and 0.12 V under positive bias stress (PBS) and negative bias stress (NBS) for 3600 s, respectively. As a demonstration of complex logic applications, a resistor-loaded unipolar inverter based on GQDs-In2O3/ZrO2 has been built, demonstrating full swing characteristic and high gain of 10.63. Low-frequency noise (LFN) characteristics of GQDs-In2O3/ZrO2 TFTs have been presented and it was concluded that the noise source can be attributed to the fluctuations in mobility. As a result, it can be concluded that solution-derived GDQ-optimized oxide-based TFTs will manifest potential applications in electronic devices.

Enteral extended biliary stents versus conventional plastic biliary stents for the treatment of extrahepatic malignant biliary obstruction: a single-center prospective randomized controlled study.

BACKGROUND AND AIMS: The main limitation of plastic stents is the relatively short stent patency due to occlusion. We designed enteral extended biliary stents with lengths of 26 cm (EEBS-26 cm) and 30 cm (EEBS-30 cm) to prolong stent patency. This study aimed to compare patency among EEBS-26 cm, EEBS-30 cm, and conventional plastic biliary stent (CPBS). METHODS: A single-center prospective randomized controlled study was conducted. Eligible patients were randomized into the EEBS-26 cm, EEBS-30 cm, and CPBS groups, respectively. All patients were followed up every 3 months until stent occlusion, patient death, or at 12-month follow-up. The primary outcome was stent patency. The secondary outcomes included stent occlusion rate, patient survival, mortality, the rate of technical success, and adverse events. RESULTS: Totally 117 patients were randomized into the three groups. There were no significant differences among the three groups in technical success rate, hospital stay, mortality, patient survival, and adverse events (P = 1.000, 0.553, 0.965, 0.302, and 0.427, respectively). Median stent patency durations in the EEBS-26 cm, EEBS-30 cm, and CPBS groups were 156.0 (95% CI 81.6-230.4) days, 81.0 (95% CI 67.9-94.1) days, and 68.0 (95% CI 20.0-116.0) days, respectively (P = 0.002). The EEBS-26 cm group had longer stent patency compared with the CPBS (P = 0.007) and EEBS-30 cm (P < 0.001) groups. The EEBS-26 cm group had lower stent occlusion rates compared with the other groups at 6 months (48.1% vs. 90.5% vs. 82.8%, P = 0.001) and 9 months (75.0% vs. 100.0% vs. 92.9%, P = 0.022). CONCLUSION: EEBS-26 cm has prolonged stent patency and is safe and effective for the alleviation of unresectable extrahepatic malignant biliary obstruction.

Ultraviolet-Assisted Low-Thermal-Budget-Driven α-InGaZnO Thin Films for High-Performance Transistors and Logic Circuits.

Developing a low-temperature fabrication strategy of an amorphous InGaZnO (α-IGZO) channel layer is a prerequisite for high-performance oxide-based thin film transistor (TFT) flexible device applications. Herein, an ultraviolet-assisted oxygen ambient rapid thermal annealing method (UV-ORTA), which combines ultraviolet irradiation with rapid annealing treatment in an oxygen atmosphere, was proposed to realize the achievement of high-performance α-IGZO TFTs at low temperature. Experimental results have confirmed that UV-ORTA treatment has the ability to suppress defects and obtain high-quality films similar to high-temperature-annealing-treated samples. α-IGZO/HfAlO TFTs with high-performance and low-voltage operating have been achieved at a low temperature of 180 °C for 200 s, including a high µsat of 23.12 cm2 V-1 S-1, large Ion/off of 1.1 × 108, small subthreshold swing of 0.08 V/decade, and reliable stability under bias stress, respectively. As a demonstration of complex logic applications, a low-voltage resistor-loaded unipolar inverter based on an α-IGZO/HfAlO TFT has been built, demonstrating full swing characteristics and a high gain of 13.8. Low-frequency noise (LFN) characteristics of α-IGZO/HfAlO TFTs have been presented and concluded that the noise source tended to a carrier number fluctuation (ΔN) model from a carrier number and correlated mobility fluctuation (ΔN-Δµ) model. As a result, it can be inferred that the low-temperature UV-ORTA technique to improve α-IGZO thin film quality provides a facile and designable process for the integration of α-IGZO TFTs into a flexible electronic system.

[Vinegar-processed Euphorbiae Pekinensis Radix improves intestinal flora disorder and reduces colon toxicity].

The present study investigated the effect of Euphorbiae Pekinensis Radix(EPR) on intestinal flora structure before and after vinegar processing and explored the detoxification mechanism of vinegar-processed EPR. In this study, the extraction efficiency of casbane diterpenes from EPR with different solvents was investigated, and the optimal solvent was selected to enrich these components. After 14 days of intragastric administration of total diterpene extract of EPR and vinegar-processed EPR, 16 S rDNA sequencing technology was used to detect the structural changes of intestinal flora. The flora related to the intestinal toxicity of EPR was screened out based on the results of intestinal pathological damage by correlation analysis. The results showed that Soxhlet extraction with chloroform as extraction solvent could enrich Casbane diterpenes in EPR. As revealed by 16 S rDNA sequencing results, EPR could significantly change the structure of intestinal flora, which could be reversed by vinegar-processing EPR. Some intestinal flora candidates might be related to detoxification of vinegar processing. The correlation analysis of intestinal flora candidates and indexes related to intestinal mucosal injury showed that compared with EPR, vinegar-processed EPR could down-regulate the abundance of some pathogenic bacteria such as Mucispirillum, Bilophila, and Ruminiclostridium, and up-regulated some probiotics such as Enterorhabdus, Ruminococcaceae_UCG-014, Barnesiella, and Candidatus. The intestinal toxicity caused by EPR may be related to the disturbance of intestinal flora, and vinegar-processed EPR can improve intestinal flora disorder by up-regulating the abundance of probiotics and down-regulating the abundance of pathogenic bacteria to remodel the intestinal mucosal barrier and reduce toxicity.

Gut microbiota disorder caused by diterpenoids extracted from Euphorbia pekinensis aggravates intestinal mucosal damage.

Gut microbiota disorder will lead to intestinal damage. This study evaluated the influence of total diterpenoids extracted from Euphorbia pekinensis (TDEP) on gut microbiota and intestinal mucosal barrier after long-term administration, and the correlations between gut microbiota and intestinal mucosal barrier were analysed by Spearman correlation analysis. Mice were randomly divided to control group, TDEP groups (4, 8, 16 mg/kg), TDEP (16 mg/kg) + antibiotic group. Two weeks after intragastric administration, inflammatory factors (TNF-α, IL-6, IL-1ß) and LPS in serum, short chain fatty acids (SCFAs) in feces were tested by Enzyme-linked immunosorbent assay (ELISA) and high-performance liquid chromatography (HPLC), respectively. The expression of tight junction (TJ) protein in colon was measured by western blotting. Furthermore, the effects of TDEP on gut microbiota community in mice have been investigated by 16SrDNA high-throughput sequencing. The results showed TDEP significantly increased the levels of inflammatory factors in dose-dependent manners, and decreased the expression of TJ protein and SCFAs, and the composition of gut microbiota of mice in TDEP group was significantly different from that of control group. When antibiotics were added, the diversity of gut microbiota was significantly reduced, and the colon injury was more serious. Finally, through correlation analysis, we have found nine key bacteria (Barnesiella, Muribaculaceae_unclassified, Alloprevotella, Candidatus_Arthromitus, Enterorhabdus, Alistipes, Bilophila, Mucispirillum, Ruminiclostridium) that may be related to colon injury caused by TDEP. Taken together, the disturbance of gut microbiota caused by TDEP may aggravate the colon injury, and its possible mechanism may be related to the decrease of SCFAs in feces, disrupted the expression of TJ protein in colon and increasing the contents of inflammatory factors.

Lipidomics Revealed Aberrant Metabolism of Lipids Including FAHFAs in Renal Tissue in the Progression of Lupus Nephritis in a Murine Model.

Lupus nephritis (LN) is an inflammatory renal disease of patients with systemic lupus erythematosus with lots of immune complexes deposited in kidneys. Accumulated studies have demonstrated the close relationships among dyslipidaemia, inflammation, and autoimmune response, and oxidative stress in the patients. Lipids play numerous important roles in biological process and cellular functions. Herein, shotgun lipidomics was employed to quantitatively analyze cellular lipidomes in the renal tissue of MRL/lpr mice in the progression of LN (including pre-LN and LN state) with/without treated with glucocorticoids (GCs). The levels of cytokines (i.e., TNF-α (Tumor necrosis factor alpha) and IL-6 (Interleukin 6)) in the serum were measured by ELISA (enzyme-linked immunosorbent assay) kits. Renal histopathological changes and C3 deposition in the glomeruli of the mice were also determined. Lipidomics analysis revealed that the ectopic fat deposition and the aberrant metabolism of lipids that were relevant to oxidative stress (e.g., 4-hydroxyalkenal, ceramide, lysophospholipid species, etc.) always existed in the development of LN. Moreover, the anti-inflammatory FAHFA (fatty acid ester of hydroxyl fatty acid) species in the kidney tissue could largely reflect the severity of LN. Thus, they were a potential early biomarker for LN. In addition, the study also revealed that treatment with GCs could prevent the progression of LN, but greatly aggravate the aberrant metabolism of the lipids, particularly when used for a long time.

Simultaneous determination of multiple components in formula and preparations of Xiaoyaosan.

Xiaoyaosan is one of the famous formulas treating for liver, spleen and blood deficiency syndrome along Chinese history. Their five main components, paeoniflorin, ferulic acid, glycyrrhizic acid, liquiritin, and atractylenolide I are believed to partly representative of this formula. Ultra performance liquid chromatography method was newly established, UPLC BEH-C18 column (2.1 × 100 mm, 1.7 µm) with acetonitrile - 0.1% phosphate acid gradient elution system, in 0.4 mL/min and the temperature was 30 °C; Detection wavelengths were optimized separately. The five components were linear within their linear range (r ≥ 0.9991), average recovery 97.63%∼102.83%, RSD 1.88%∼4.38%. The newly established method is accurate, rapid, and convenient, with satisfied separation performance to quantify multi-components in formula and preparations of Xiaoyaosan. It will provide a reliable reference for the quality evaluation of both Xiaoyaosan formula and preparations during the process of manufacture, administration and clinical application in the future.

Determination of Differentiating Markers in Coicis Semen From Multi-Sources Based on Structural Similarity Classification Coupled With UPCC-Xevo G2-XS QTOF.

Coicis semen, a medicinal food, is derived from the dried and mature seeds of Coix lacryma-jobi L. var. ma-yuen (Rom.Caill.) Stapf, a member of the Gramineae family. Lipids are its main constituents. Previous literature reported that coicis semen contains twenty triglycerides and twelve diglycerides. However, we identified thirty-five triglycerides, sixteen diglycerides, four monoglycerides, and two sterols under the preoptimized conditions of UPCC-Xevo G2-XS QTOF combined with a personalized TCM database. Furthermore, we successfully determined glycerol trioleate content to evaluate quality differences. Finally, we identified the fatty acid compositions of seven out of nine differential markers via Progenesis QI using principal component analysis, orthogonal projection to latent structures-discriminant analysis, and the LipidMaps database. In addition, we applied a software-based classification, a method that was previously developed by our team, to verify and predict structurally similar compounds. Our findings confirmed that UPCC-Xevo G2-XS QTOF combined with software-based group classification could be used as an efficient method for exploring the potential lipid markers of seed medicine.

Nephrotoxicity of Herbal Medicine and Its Prevention.

Herbal medicine (HM) has been widely used to treat diseases for thousands of years and has greatly contributed to the health of human beings. Many new drugs have been developed from HM, such as artemisinin. However, artemisinin has adverse effects, such as renal toxicity. In 1993, a study conducted in Belgium reported for the first time that the root extracts of Aristolochia obliqua S. M. Hwang led to progressive interstitial renal fibrosis. The nephrotoxicity of HM has attracted worldwide attention. More than 100 kinds of HM induce renal toxicity, including some herbs, animal HMs, and minerals. This paper aimed to summarize the HM compounds that cause nephrotoxicity, the mechanisms underlying the toxicity of these compounds, biomarkers of renal injury, and prevention strategies. These findings provide a basis for follow-up studies on the prevention and treatment of HM nephrotoxicity.

The Phytochemistry, Pharmacology, and Quality Control of Tetrastigma hemsleyanum Diels & Gilg in China: A Review.

Tetrastigma hemsleyanum Diels & Gilg (TDG), the family member of Vitaceae, is a traditional herbal medicine in China. The root of TDG can be immediately used after cleaning the muddy soil, and can be dehydrated for dry use. TDG is able to be collected all year round, which is commonly used in the treatment of hepatitis, infantile high fever, snake bite, etc. Based on phytochemistry, the chemical components of TDG are divided into flavonoids, phenolic acids, terpenes, steroids, polysaccharide, and other compounds, showing many pharmacological effects which include anti-tumor, anti-oxidation, anti-inflammatory, antipyretic, analgesic, and immunomodulatory activity, as well as other activities. Currently, TDG involves some problems of the reduction of wild resources, the backward processing methods, and storage difficulties as well as the imperfection of detection methods. Therefore, this review summarizes the literature of the past 20 years, and the purpose of this review is to summarize the recent researches on the phytochemistry, pharmacology, quality control, and clinical application of TDG. The above discussions provide new insights for the future research on TDG.

Transfer of metastatic traits via miR-200c in extracellular vesicles derived from colorectal cancer stem cells is inhibited by atractylenolide I.

Cancer stem cells (CSCs) are important factors contributing to tumorigenesis. We examined whether CSCs isolated from colorectal cancer (CRC) cells possess metastatic properties that can be transferred to non-CSCs via the delivery of miR-200c enclosed in extracellular vesicles (EVs). The inhibitory effect of atractylenolide I (ATL-1), a traditional Chinese medicinal compound, on miR-200c activity and metastatic transfer was investigated. EVs were isolated from colorectal CSCs. The expression of miR-200c was evaluated in CSCs and CSC-derived EVs, and horizontal transfer of metastatic properties via EVs to non-CSCs was investigated in terms of cell behavior and phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling. CSCs isolated from metastatic CRC cells exhibited higher levels of miR-200c than those in nonmetastatic CRC cells. Overexpression of miR-200c in CSCs enhanced metastatic potential by promoting proliferation and inhibiting apoptosis, in turn leading to the release of EVs carrying an excess of miR-200c. Non-CSCs co-cultured with miR-200c-containing EVs exhibited enhanced invasion and stemness maintenance associated with PI3K/Akt/mTOR activation, demonstrating successful metastatic transfer via EV delivery. Furthermore, ATL-1 impaired the EV-mediated transfer of metastatic properties by suppressing miR-200c activity and disrupting EV uptake by non-CSCs. EVs are critical signal transducers that facilitate intercellular communication and exchange of metastatic properties, which can be controlled by ATL-1. The findings are useful in the development of microRNA-based anticancer strategies by targeting EV-mediated activity, especially using natural compounds.

Atractylenolide I inhibits colorectal cancer cell proliferation by affecting metabolism and stemness via AKT/mTOR signaling.

BACKGROUND: Atractylenolide I (ATL-1) is a natural herbal compound used in traditional Chinese medicine that has exhibited anti-cancer properties. The anti-tumorigenic activity of ATL-1 against colorectal cancer (CRC) and the underlying signaling pathways involved in its mechanisms are examined here. HYPOTHESIS: ATL-1 exerts therapeutic effect against CRC by disrupting glucose metabolism and cancer stem cell maintenance via AKT/mTOR pathway regulation. STUDY DESIGN: In vitro studies were performed in COLO205 and HCT116 CRC cell lines and in vivo studies were conducted in a mouse xenograft model of CRC tumor. METHODS: CRC cells were treated with ATL-1 at various concentrations, with or without inhibitors of AKT or mTOR. Cell proliferation, apoptosis, invasion, stemness maintenance, glucose metabolism, and AKT/mTOR signaling were evaluated. CRC tumor-xenografted mice were treated with an AKT inhibitor and/or ATL-1, and glucose metabolism and stemness maintenance were examined in tumor tissues. RESULTS: ATL-1 significantly inhibited the invasion of CRC cells by inducing their apoptosis, possibly via the excessive production of reactive oxygen species. Glucose metabolism (Warburg effect) was also altered and stem-like traits were suppressed by ATL-1. In addition, ATL-1 effectively acted as an inhibitor or AKT/mTOR by downregulating the phosphorylation of proteins related to the AKT/mTOR pathway. In vivo studies showed that tumor weight and volume were reduced by ATL-1 and that aerobic glycolysis, stemness maintenance, and AKT/mTOR activation were impaired by ATL-1 in colorectal tumors. CONCLUSIONS: ATL-1 acts as an effective agent to suppress colorectal tumor progression, mainly by inhibiting CRC cell proliferation through altering apoptosis, glucose metabolism, and stem-like behavior. These processes were mediated by the AKT/mTOR signaling pathway both in vitro and in vivo. ATL-1 may be a potential agent to be used in molecular-targeted strategies for cancer treatment.

Extrusion of Dissolved Oxygen by Exopolysaccharide From Leuconostoc mesenteroides and Its Implications in Relief of the Oxygen Stress.

Strains of Leuconostoc are generally facultatively anaerobic and exposure to oxygen might be detrimental; therefore, strategies to combat the oxygen stress are essential for these bacteria to survive and flourish in the oxygenic atmosphere. Despite the extensive applications in industry, the fundamental issues concerning the aerobic life of Leuconostocs remain to be addressed. In this study, we have demonstrated that Leuconostoc mesenteroides CGMCC10064 cultivated in sucrose medium would acquire a growth advantage over that in glucose medium under oxygenic conditions, as reflected by more viable cells and less accumulation of reactive oxygen species. Further analysis showed that the growth advantage was dependent on exopolysaccharide (EPS) synthesized by a secreted glucansucrase. Determination of the dissolved oxygen in the culture suggested that the growth improvement was mediated by extrusion of dissolved oxygen from the aqueous circumstances. Growth experiments performed with the purified EPS showed that supplementation of 5 g/L EPS in the medium could improve the aerobic growth of L. mesenteroides by ∼10-fold. Moreover, the purified EPS was also effective in promoting the aerobic growth of oxygen-sensitive Lactobacillus and Bifidobacterium. These results demonstrate that EPS of L. mesenteroides plays a critical role in relief of the oxygen stress, and suggest the potential of the EPS in manufacture as well as preservation of oxygen-sensitive probiotics.